diff --git "a/store/embed_openai/docstore.json" "b/store/embed_openai/docstore.json"
new file mode 100644--- /dev/null
+++ "b/store/embed_openai/docstore.json"
@@ -0,0 +1 @@
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They have important roles as connective tissues, provide structural support and barriers, have roles in development, and mediate intercellular communication. These structures include the cuticle (see also Cuticle Section and Dauer Cuticle), the pseudocoelom, extracellular matrices, basal laminae, as well as the eggshell and the embryonic sheath of the embryo.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 466, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "51d740ba-3539-4463-98f3-f2d319dbb21e": {"__data__": {"id_": "51d740ba-3539-4463-98f3-f2d319dbb21e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 2) Pseudocoelom](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "51730910-ccc0-4275-8889-57a0fdfdda2f", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 2) Pseudocoelom](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "hash": "74b5b3e5c9ccabd51bee0e3fb58f4a0d7726aa5b84bf78c598f2f8b8f3ec7669", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The pseudocoelom is a fluid-filled body cavity lying inside the external body wall of the nematode that bathes the internal organs, including the alimentary system and the reproductive system (PeriFIG 1). This body cavity is called a \u00e2\u0080\u009cpseudocoelom\u00e2\u0080\u009d because it is not fully lined by mesodermal cells as in the true \u00e2\u0080\u009ccoelomic cavity\u00e2\u0080\u009d of vertebrates. The C. elegans pseudocoelom is bounded by basal laminae (BL) that cover the hypodermis, the nervous tissues, the gonad and the intestine (PeriFIG 2) (Bird and Bird, 1991). The pseudocoelom contains the coelomocytes (see Coelomocyte Section), provides the turgor-hydrostatic pressure for the animal as a whole, functions as a lubricant between tissues, and provides a medium for intercellular signaling and nutrient transport.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 781, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "459e8f7e-e82c-4163-9cd5-52a52d4c615d": {"__data__": {"id_": "459e8f7e-e82c-4163-9cd5-52a52d4c615d", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 2) Pseudocoelom](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8ff8a940-6c46-4c45-bfe5-95bb7a3fe04b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 2) Pseudocoelom](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "hash": "2af4a56ee7f7b2b4c2df117cc81d2c006465fa588560a25993ca0742111d2756", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The pseudocoelomic fluid is restricted from reaching the cuticle by a series of barrier junctions that link every cell type in the bodywall\u00e2\u0080\u0099s epithelial system, particularly the belt junctions (adherens  junctions) of the hypodermis. Similarly, the pseudocoelomic fluid cannot mix with the luminal contents of the digestive tract nor the reproductive tract due to the presence of another permeability barrier: the belt junctions connecting all epithelial cells in those tissues. The permeability barrier between the gut lumen and the pseudocoelom is particularly important since it prevents leakage of digestive enzymes, stray bacteria, or viruses into the body cavity. Thus, the pseudocoelom is effectively isolated from other body fluids, while bathing all tissues on their basal pole with similar contents. As a result, the pseudocoelom is positioned to carry out many of the functions normally performed by the circulatory system (bloodstream) or the respiratory system (airways) in higher animals. Motions of the nematode\u00e2\u0080\u0099s body may effectively stir the contents, but otherwise there is no active circulation per se. The permeability barriers on both sides of the pseudocoelom also allow the pseudocoelomic fluid to be pressurized beneath the elastic cuticle; thus, the fluid acts as a hydrostatic skeleton that contributes to maintain the nematode\u00e2\u0080\u0099s overall rigidity (Crofton, 1966). In aging worms, this hydrostatic pressure is often decreased.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1457, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2724ef8b-6c26-460b-bb41-190ca6eec0ad": {"__data__": {"id_": "2724ef8b-6c26-460b-bb41-190ca6eec0ad", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 2) Pseudocoelom](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9bf13d95-0164-49db-baa6-049124e5452e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 2) Pseudocoelom](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "hash": "d14b947b9140bf9407244a6ffaedf016b7bbc955eb1feed3699b749222a05ca3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The pseudocoelomic space forms later in embryonic morphogenesis, and its fluid contents first derive from the fluid bathing the early blastomeres, the blastocoel.\u00a0 It is present in the adult and in all larval stages. The cross-sectional volume of the pseudocoelom is larger along the midbody regions, but becomes much tighter and less voluminous in the head and in the tail tip. Because this fluid is in contact with all major tissues, it helps to establish an ionic equilibrium for the whole animal, balancing the osmotic contents of the various tissues. The chemical composition of the pseudocoelomic fluid has been analyzed in larger nematode species and was found to have a neutral pH and to contain proteins, fat, glucose, sodium, chloride, magnesium, phosphorus, and small quantities of copper, zinc, iron, hematin and ascorbic acid. The main buffering system in the pseudocoelomic fluid of larger nematodes was found to be bicarbonate:phosphate (Bird and Bird 1991).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 973, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8a76f92e-8e9b-4abb-806c-95d271ce1870": {"__data__": {"id_": "8a76f92e-8e9b-4abb-806c-95d271ce1870", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 2) Pseudocoelom](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a1c3b0f8-dd56-479c-8e0a-0f34ff416267", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 2) Pseudocoelom](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "hash": "1cab6663234a47ee122154bffae2a6ef3d288debec430d50f5ac41aa6b73316b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Laser ablation experiments and mutant analysis have implicated the excretory system, the canal-associated (CAN) neurons and the hypodermis as important regulators of ionic and fluid homeostasis in C. elegans (Nelson and Riddle, 1984; Forrester et al., 1998; Huang and Stern, 2004). The pseudocoelom is in close physical contact with the excretory canals along the length of the midbody and in the head, and the CANs have close association with the canals (ExcFIG 4 and ExcFIG 7). The excretory canals also form extensive gap junctions to the hypodermis that may play a role in coupling their influences on fluid balance. Ablation of the excretory system cells or the CAN neurons, or hyperactivating EGL-15 (an FGF-like receptor tyrosine kinase) or CLR-1 (a receptor tyrosine phosphatase) in hypodermis results in a Clr (clear) phenotype, characterized by the accumulation of clear fluid within the pseudocoelomic space (Huang and Stern, 2004). The excretory system and hypodermis are thought to regulate fluid homeostasis by regulating fluid outflow and inflow, respectively. The hypodermis functions to either promote fluid intake or inhibit fluid excretion, whereas the excretory system functions in disposing solutes and water that pass into the canal cell from the pseudocoelom (see Excretory System).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1305, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "804d8376-f38d-4166-8841-c7974972d0b3": {"__data__": {"id_": "804d8376-f38d-4166-8841-c7974972d0b3", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 2) Pseudocoelom](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5b5cc48c-7aef-4796-b4bd-09fb6e10fcf8", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 2) Pseudocoelom](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "hash": "c1c422258598ead27c969be854c388d84caca4fe2a693584b6d080d88706443e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The coelomocytes continuously and nonspecifically endocytose fluid from the pseudocoelomic fluid (CcFIG 5). These cells perform a primitive immune surveillance function for the animal, while floating within this fluid (see Coelomocyte System). The coelomocytes can recognize substances, viruses, or invading bacteria that do not belong inside the animal and degrade them. Thus, solid waste materials can be disposed by the coelomocytes, whereas liquid waste is excreted from this cavity via the excretory system.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 512, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "33aed740-c0b2-4f6e-9d0e-9ae70258821e": {"__data__": {"id_": "33aed740-c0b2-4f6e-9d0e-9ae70258821e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 2) Pseudocoelom](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4dd8be35-db0e-4e03-b4f5-51bbb3e0ddc6", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 2) Pseudocoelom](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "hash": "73c87ba2ae10c43b22f0f04300e4116356f64b929318d66e9bb64e6f32cec97a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Previously, it was noted that GLR processes seal off the pseudocoelomic space at the anterior edge of the nerve ring, suggesting that this space may not extend further than the posterior isthmus (White et al., 1986) (see Muscle System - GLR cells). However, a narrow space between the pharynx and the surrounding tissues is observed even anterior to that locale, and may be considered an \u00e2\u0080\u009caccessory pseudocoelom\u00e2\u0080\u009d (Altun and Hall, unpublished; J. White, pers. comm.). This narrowed accessory pseudocoelom may share the same functions as the main pseudocoelom, and it is likely that extracellular signals can pass between them. For instance, some signals that seem to affect the entire animal could be released into this narrow space, including the lipophilic hormones secreted by the XXX cells (see Epithelial System - Atypical Cells; AtypFIG 3) (Jia et al 2002; Gerisch and Antebi, 2004). Similarly, the NSM neurons have neurohumoral release zones extending to both sides of the GLR constrictions, suggesting that it is important to release their product into the accessory space as well as into the main portion of the pseudocoelom. Additionally, fluorescently labeled antibodies injected into the body pseudocoelom can diffuse and label extracellular peripheral membrane ligands in the anterior head (Gottschalk and Schafer, 2006). The accessory pseudocoelomic space ends near the anterior limit of the pharyngeal muscles after narrowing further in a graded fashion.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1472, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "88cb52ea-975a-4920-a25b-028d6a214e37": {"__data__": {"id_": "88cb52ea-975a-4920-a25b-028d6a214e37", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 2) Pseudocoelom](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c21f12eb-4679-4d96-8e88-033ef4646b02", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 2) Pseudocoelom](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "hash": "e7b1b8d9ede6da69104a2e9204991d6b60349dfcbda5243854d05326bbcb4e4e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The pseudocoelomic fluid may reduce friction between adjacent tissues (during feeding) since vigorous motions of the pharynx occur, with no apparent drag on the nearby bodywall. Similarly, the extension of the gonad during larval stages and contraction of the body wall muscles during locomotion do not lead to major observable changes in the body form, highlighting the flexibility afforded by this cavity.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 407, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5bc4a226-2602-4f15-874d-2fe3b3d20f5e": {"__data__": {"id_": "5bc4a226-2602-4f15-874d-2fe3b3d20f5e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 2) Pseudocoelom](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "160f8b13-5510-48bd-88f8-8558964b6db2", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 2) Pseudocoelom](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "hash": "b90f5d2f81a050187a9ed9084e891889430bae36e88990969c3102748d1de654", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "There are relatively few structures spanning the width of the pseudocoelomic cavity in any locale. Two minor axons span the gap to connect the pharyngeal nervous system to the rest of the nervous system. Also in the head, long flexible tendons cross the pseudocoelom to link the basal lamina of the outer bodywall in the head to the pharynx (Muriel et al., 2005; Ax\u00c3\u00a4ng et al., 2007).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 384, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6bad7adf-26f4-45fa-9b60-fa6f57397167": {"__data__": {"id_": "6bad7adf-26f4-45fa-9b60-fa6f57397167", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 2) Pseudocoelom](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1f95f794-5ebf-4e37-bdb8-f384c23fcfc4", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 2) Pseudocoelom](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "hash": "6115b60b45829046d26d34ae07b61108f2d81b2b545eb2da0ee1013a5d13c3ea", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Given the exposure of all tissues to this body cavity, many cell types can use the pseudocoelomic fluid as a route for signaling between  tissues, as well as to transfer useful (nutritive) materials, including yolk protein and oxygen. The exact balancing of oxygen levels within the animal is not well understood, but it is clear that neuronal oxygen-sensing cells have their cell body and/or cilium located within this cavity to monitor the animal\u00e2\u0080\u0099s net oxygen levels (see Nervous System; de Bono and Bargmann, 1998; Cheung et al., 2005). \u00a0Several proteins with homologies to myoglobin or hemoglobin are present in high titer within the nematode pseudocoelom and potentially can act as carriers (or sensors) for oxygen, nitric oxide, or other gases (De Baere et al., 1992; Minning et al., 1999; Hoogewijs et al., 2004).\u00a0 Alternately, it might be more important for these proteins to act as carriers for hemin, an essential enzyme cofactor that can be toxic if unbound (Rao et al., 2005; I. Hamza, pers. comm.).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1013, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "03ac04ea-fa0c-4d82-b784-bad1d0f1ec4b": {"__data__": {"id_": "03ac04ea-fa0c-4d82-b784-bad1d0f1ec4b", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 2) Pseudocoelom](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bf9f7d8b-c481-4290-adfe-08e063e54ec9", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 2) Pseudocoelom](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "hash": "61b5aaad3b3dbbbf481ae1f7c8136340067fb2bf021831536e122ce2c80cb2c9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In C. elegans, yolk is secreted from the intestine, its primary site of synthesis, into the pseudocoelomic space as free-floating granules and is ultimately shuttled to the reproductive tract. Yolk granules then go through sheath pores to the surface of the oocyte, where they are taken up into vesicles within the growing oocytes (PeriFIG 2C) (Kimble and Sharrock, 1983; Sharrock, 1983; Hall et al., 1999). Yolk synthesis starts during L4 lethargus and continues through the adult life. The net direction of yolk transport is reversed during embryonic development; during\u00a0 midembryogenesis, nonintestinal cells resecrete the yolk they inherited from the oocyte into the perivitelline space, which is then taken up by the intestinal cells. At  hatching most of the yolk is therefore stored in the intestine (Bossinger and Schierenberg 1996; Grant and Hirsh, 1999). When reproductive life has ended, excess yolk begins to collect within the body cavity to form huge islands of material (Herndon et al., 2002).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1008, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6e000cd9-d4ae-47b7-b6e2-cda27fc5a37d": {"__data__": {"id_": "6e000cd9-d4ae-47b7-b6e2-cda27fc5a37d", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 3) Extracellular Matrix](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "dfc364af-deb8-40f7-a57d-c81b90b0a684", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 3) Extracellular Matrix](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "hash": "0588ad080a272355ff8a066e2d1d370d7aebe250df854529de14cb3d1e8627d9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The local environment on the outside of each cell or tissue can be complex because a variety of nearby cells may contribute components to it. Some of these components, such as glycoproteins and carbohydrates, quickly become deposited into distinct extracellular layers near their origin of synthesis generating extracellular matrices (ECM), but others may diffuse more widely as intercellular signals. The major ECM are the basement membrane, which covers the basal surfaces of the tissues, and the cuticle on the outside of the animal (PeriFIG 2 and PeriFIG 3A) (see Cuticle). There are other, smaller matrices that are specific to certain tissues, such as the mantle, rachis coat, tendons and zona pellucida. A number of very long fibrous proteins and glycosaminoglycans (proteoglycans) are secreted into the extracellular space that may then  condense to form the basement membranes or may attach to the ECM in a less orderly fashion and extend into the pseudocoelomic fluid (Kramer, 2005). For instance, the very long DIG-1 protein is probably attached to the basement membrane, but has been hypothesized to extend far into the cavity (B\u00c3\u00a9nard et al., 2006). Depending on how one prepares the adult animal for microscopy, the ECM has a variable appearance.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1260, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "bae1249d-958d-4cf5-91d7-e537221c6fb3": {"__data__": {"id_": "bae1249d-958d-4cf5-91d7-e537221c6fb3", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 3) Extracellular Matrix](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e8a7fbe3-346b-42b2-adb9-8051e7073374", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 3) Extracellular Matrix](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "hash": "712e1717ce6d67ffbbe119e1fb9b5dbbd8986a3df563ee9fa11c7e0ff33a2220", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Not much is known about the conformation of any of the large proteins and proteoglycans of the ECM, particularly in their native state within the animal.\u00a0 Intramolecular binding sites and post-secretion modifications of these proteins help to bind them into larger mesh-like structures in the basement membrane.\u00a0 This meshwork can serve to bind smaller signaling molecules into place within the cavity. As a result, important signals for cell fate and cell polarity decisions, cell migration, process extension and synaptogenesis are presented to each tissue from the ECM.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 572, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cbbb53de-fe54-4b94-bd8b-541c6825b372": {"__data__": {"id_": "cbbb53de-fe54-4b94-bd8b-541c6825b372", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 3) Extracellular Matrix](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "17c35bcc-f0ba-47e7-b672-bc144ade7bae", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 3) Extracellular Matrix](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "hash": "3b2000f2ddd713f4de1f9671e4e6c40c8cbfb7db8706a4aad01fb188fd60195f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Beginning in mid to late morphogenesis in the embryo, the ECM begins forming and from this time forward it may present a physical barrier to cell movements as cells try to shuffle past each other to form proper groupings. Migrating cells or cell processes may use instructive signals within the matrix to direct their progress (Hedgecock et al., 1987; Merz et al., 2003; Hilliard and Bargmann, 2006; Prasad and Clark, 2006). Some migrating cells secrete degradative enzymes (matrix metalloproteinases) to open holes in the matrix locally to make progress in certain directions (Wada et al., 1998; Blelloch and Kimble, 1999; Meighan et al., 2004; Sherwood et al, 2005). Late larval changes in the male tail also involve dramatic reformation of the ECM (Kuno et al., 2002).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 771, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f8d7fd49-fc00-496e-93df-7c9a18e98c69": {"__data__": {"id_": "f8d7fd49-fc00-496e-93df-7c9a18e98c69", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 3) Extracellular Matrix](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bb43e106-dec5-462d-a983-4bb251c512d6", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 3) Extracellular Matrix](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "hash": "5f3e479aa230b72cb9e97d2a866e607d017a21e768ccad78c37887f5c63a24c6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Certain molecules appear to be able to pass across the ECM at will, even where a robust basement membrane is evident. At neuromuscular junctions in the adult, neurotransmitters (e.g. acetylcholine or \u00ce\u00b3-aminobutyric acid) must pass through the matrix lying between neurons and muscle arms. Yolk protein granules floating in the pseudocoelomic fluid are able to cross the basement membrane covering the gonad (Hall et al., 1999).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 428, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "31c139df-f096-4209-83b6-3e4f948a5804": {"__data__": {"id_": "31c139df-f096-4209-83b6-3e4f948a5804", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 3) Extracellular Matrix](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8f6c62a4-6a9a-4160-88da-110729b9d7e5", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 3) Extracellular Matrix](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "hash": "2d07784b3c139774e7ceced8f857f9535c067bc7a35632d63f41396df63fc708", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "3.1 Basement Membrane (Basal Lamina)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 36, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "16bbd2bb-9719-4975-acba-66b1feaf3129": {"__data__": {"id_": "16bbd2bb-9719-4975-acba-66b1feaf3129", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 3.1) Basement Membrane (Basal Lamina)](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0e9e5ed2-28bf-4b6d-a0fd-86bfc6748199", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 3.1) Basement Membrane (Basal Lamina)](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "hash": "b8561322ade778ba31aa6a6d74451fe1d3348d24913d8253048f0b53876de9a7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Besides cuticle, the most prominent extracellular structure associated with most cells is the basement membrane, which formally includes the basal lamina (BL) and an external layer, the reticula lamina (see Basement Membranes chapter in WormBook for more detail - Kramer, 2005). In the nematode, it is generally impossible to distinguish these separate features, and thus the two terms basement membrane and basal lamina are often used interchangeably. In higher animals, the BL itself can be viewed by electron microscopy to constitute a multi-layered structure, but this is not true in C. elegans. Instead the BL appears as a unitary thin layer covering the basal surface (pseudocoelomic side) of tissues in the nematode (Huang et al., 2003). Each tissue lying across the pseudocoelom is covered separately by its own lamina.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 827, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4218dfd6-0393-4e38-89e7-379e8770d2d3": {"__data__": {"id_": "4218dfd6-0393-4e38-89e7-379e8770d2d3", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 3.1) Basement Membrane (Basal Lamina)](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "99e95d8d-0219-4d76-a190-d5df882c1f25", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 3.1) Basement Membrane (Basal Lamina)](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "hash": "38b09b02a96dc8ae3236067b025212a779b3c0e2c15662a9360643f62a82eecc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The width of the basal lamina tends to be almost unitary for any one tissue, but varies widely (between 20-100 nm) between tissues (Huang et al., 2003). In a few tissues (e.g., bodywall muscle), periodic rod-like structures are seen lying on the outside of basal lamina that might represent either a 2nd layer or a reticula lamina. The BL of the pharynx is particularly thick and robust (PhaFIG 5D). In certain regions, the BL shows specializations that may strengthen it or permit stronger binding between adjacent tissues. For example, the uterine epithelium is firmly attached to the lateral bodywall via a local thickening of the BL at the seam cell (EggFIG 3).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 665, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5504d369-e5ff-4e52-90ba-d5ff3eb0287f": {"__data__": {"id_": "5504d369-e5ff-4e52-90ba-d5ff3eb0287f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 3.1) Basement Membrane (Basal Lamina)](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e22b514a-d07a-42c8-988a-c3ec831dd522", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 3.1) Basement Membrane (Basal Lamina)](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "hash": "d2e292b4c0dc9c107bbf7abe0e986eae2bbd1327afc039ef51e964f55d50846b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In certain locales, two separate basal laminae may merge  into a wider unitary structure to link different tissues firmly together. In particular, the outer face of the bodywall muscles links tightly to a thin outer layer of hypodermis via the merger of their respective basal laminae. Fibrous organelles that traverse these tissues anchor each muscle to the cuticle (see Somatic Muscle; MusFIG 11).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 399, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "51d13566-c4fa-4c39-bbd6-f93b1303b3ca": {"__data__": {"id_": "51d13566-c4fa-4c39-bbd6-f93b1303b3ca", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 3.1) Basement Membrane (Basal Lamina)](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3e746dd7-ed1b-4d2a-93f7-c52f7ba6815e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 3.1) Basement Membrane (Basal Lamina)](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "hash": "9788253706621ab29d6c20bc2ccdd9842d28d14ecd149d890aacd895a59b31f8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The principal molecular components of the nematode BL typically include an inner meshwork of laminins and collagen IV and, rarely, an outer layer of rod-like collagen fibrils (Kramer, 2005). Expression and genetic data suggest that laminins are essential for early embryonic basement membrane assembly and, in the absence of laminin deposition, no other basement membrane component can initiate the assembly of the basement membranes (Yurchenco and Wadsworth, 2004). After laminin deposition, other basement membrane components are integrated into the nascent laminin scaffold. One of these, collagen IV, which is synthesized by the gonad and the muscle, is absent from the BL of the hypodermis and the muscle in regions that face the pseudocoelomic space\u00a0 (PeriFIG 2) (Graham et al., 1997). Similar to the basement membranes in higher animals, the basement membranes of C. elegans are decorated by a variety of linking molecules including nidogen (entactin), collagen XVIII, and heparan sulfate proteoglycan (perlecan) (Hutter et al., 2000; Yurchenco et al., 2004). Also attached to this matrix are a wide variety of signaling molecules and growth factors, including netrin, slit, wnt, SPARC and others (Schwarzbauer and Spencer, 1993; Wadsworth et al., 1996; Kang and Kramer, 2000; Pan et al., 2006; Quinn et al., 2006). The BL is often physically linked to the underlying plasma membrane by cell adhesion molecules (CAMs), including integrins and dystroglycan, and perhaps via sulfated glycolipids and proteoglycans (syndecan) (Yurchenco et al., 2004; Kramer, 2005). Hemicentin, which is synthesized by the gonadal leaders and bodywall muscles, is integrated into specialized matrices, including the mantle of the touch  dendrites, the BL associated with the longitudinal nerve cords and nerve ring, the uterine-seam attachment, apical surfaces that surround the rachis of the germline, and the tendons around the pharynx (PeriFIG 3 and PeriFIG 4) (Vogel and Hedgecock, 2001). It is also secreted by the anchor cell in early L3 stage securing the anchor cell to the BL prior to cell invasion during vulva morphogenesis (Sherwood et al., 2005).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2146, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "00b42e41-fc51-4688-a29f-a01889476cc9": {"__data__": {"id_": "00b42e41-fc51-4688-a29f-a01889476cc9", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 3.2) Specialized Extracellular Matrices](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1edf31fc-549a-4585-93ea-81996fcd5432", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 3.2) Specialized Extracellular Matrices](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "hash": "e8417cb14037de16d7362294cc26251765b7b5fa089a593f682c4fe6122e9af6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The main processes of four mechanosensory (ALM, PLM) neurons are bounded by a specialized extracellular matrix, called the mantle, which helps to maintain the processes in close association with the cuticle and is part of the mechanical coupling between the cuticle and the nerve membrane (NeuroFIG 9D) (Hekimi and Kershaw, 1993). Fibrous organelle-like structures, formed by the neighboring hypodermis, are positioned periodically along the length of the touch receptor process, in close contact with the mantle on the cuticle side (NeuroFIG 9E-G). These are thought to be the sites at which the touch receptor process is anchored to the cuticle via the ECM (Tavernarakis and Driscoll, 1997). Mantle proteins are synthesized by the touch receptor neurons, hypodermis and muscle, and they include a mantle-specific collagen (MEC-5), hemicentin (HIM-4), and other matrix proteins such as MEC-9 and MEC-1 (Du et al., 1996; Vogel and Hedgecock, 2001). Mantle proteins organize the placement of the receptor (degenerin) channel complex in the nerve process and are believed to be important for mechanotransduction, although the attachment of the nerve process to the body wall per se is not essential for touch sensitivity (see Nervous System; Vogel and Hedgecock, 2001; Emtage et al., 2004; O\u00e2\u0080\u0099Hagan and Chalfie, 2006).\n\n3.2.2 Rachis Coat", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1336, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6b39a8f9-12d9-4407-912c-f1a79f078678": {"__data__": {"id_": "6b39a8f9-12d9-4407-912c-f1a79f078678", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 3.2) Specialized Extracellular Matrices](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "061d216b-9cba-4402-be17-a6b9fb3fc12d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 3.2) Specialized Extracellular Matrices](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "hash": "09735781b7734995e6c9d38bdafdfeaafdda9204d65656a115e91c31456a3ed8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The apical surface of the plasma membrane that surrounds the central rachis of each gonad arm is covered by a uniform layer of ECM called the rachis coat, which is mainly composed of hemicentin (HIM-4) (PeriFIG 3) (Vogel and Hedgecock, 2001; Hall, unpublished). At hatching, hemicentin is seen in the lateral extracellular space between the germline cells. Later, as the germ cells proliferate, hemicentin accumulates as a 0.2- to 0.3-\u00ce\u00bcm-thick layer on the apical surfaces of the distal gonad in a quasihexagonal distribution. More proximally, a diffuse sheet of hemicentin surrounds the rachis along the meiotic germ cells. The hemicentin layer may help to reinforce the isolation of adjacent spindles in the cortical layer of the mitotic germline syncytium and prevent abortive cytokinesis and sporadic cell refusion, because frequent mitotic chromosome loss and binucleate germline cells are found in hemicentin mutants (Vogel and Hedgecock, 2001). The rachis coat may also function in oocyte maturation (see Reproductive System - Germline).\n\n3.2.3 Fibrous Connective Tissue: Tendonous Structures", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1100, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5485cdae-45b5-44d7-a611-a1d2c6d83d0c": {"__data__": {"id_": "5485cdae-45b5-44d7-a611-a1d2c6d83d0c", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 3.2) Specialized Extracellular Matrices](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b3400c67-fbbf-4926-b63c-80598d20c741", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 3.2) Specialized Extracellular Matrices](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "hash": "4ba10bf1115d64401f434582595f3e759191efbd1bd04e82759a247b2d4d4f62", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Four rows of radially extending, elongated tendonous structures (also called \u00e2\u0080\u009cflexible tracks\u00e2\u0080\u009d) link the BL of the pharynx to the merged BL of the body wall muscles and hypodermis (PeriFIG 4) (Muriel et al., 2005; Bumbarger et al., 2006; Ax\u00c3\u00a4ng et al., 2007). These tendonous tracks run radially outward from the pharynx and pass directly between muscle pairs in each muscle quadrant in the head to reach the muscle-hypodermis BL. Besides the RIP neuron processes, they are the only documented structures to span the width of the pseudocoelom. Each tendon row contains at least six to eight tendons as judged by electron microscopy (TEM). The principal known components of these tendons are hemicentin and fibulin (Vogel and Hedgecock, 2001; Muriel et al., 2005). As the animal moves, tendons anchored at each end by merging with BL can change dramatically in length. They flex during pharyngeal pumping and shift in orientation as the pharynx changes in length to tilt obliquely forwards or backwards. These motions suggest the tendons may help to hold the pharynx in position within the bodywall. In certain mutations that cause twisting of the overall pharynx structure, these tendons can stretch even more dramatically without rupture, retaining their anchorage points and becoming twisted around the outside of the distorted pharynx (Ax\u00c3\u00a4ng et al., 2007). Other hemicentin tracks run along the anterior-posterior axis between the intestine and bodywall, but are not clearly anchored on either end (Vogel and Hedgecock, 2001; Hall, unpublished).\n\n3.2.4 Oocyte Covering (Zona Pellucida)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1593, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "597cdc7f-00b1-437f-bded-8001e6e40349": {"__data__": {"id_": "597cdc7f-00b1-437f-bded-8001e6e40349", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 3.2) Specialized Extracellular Matrices](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3c6565ff-7983-472f-a2e3-2412fc825208", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 3.2) Specialized Extracellular Matrices](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "hash": "e404dc271b2e9b4b14e9b9d43966874409f8aca1f2294562bcf1277bdf04b951", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Each unfertilized primary oocyte briefly forms a visible basal lamina while lying within the somatic gonad, just before entering the spermatheca (PeriFIG 2). This layer appears to include laminin (Huang et al., 2003), and probably includes other extracellular matrix components that may be equivalent to ZP glycoproteins of the zona pellucida. This layer is not known to hinder fusion of the oocyte and spermatocyte, and some components may contribute afterwards to the fertilization membrane.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 493, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d0083208-4b40-4e07-a8a1-e76735a63055": {"__data__": {"id_": "d0083208-4b40-4e07-a8a1-e76735a63055", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 4.4) Sheath Cell](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d4fa77ec-f1e6-4d17-ae01-b89fb5016ff8", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 4.4) Sheath Cell](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "hash": "102d314b22b5c48c09e1dd21921314e9e7a8f8293821bc7f0bb8fd4be23cc50c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The lumen of the amphid sheath cell encloses the dendrites of the amphid neuron cilia, and is also open to the exterior of the animal.\u00a0 Surrounding the dendrites, the luminal volume is completely filled with an electron-dense material that is secreted from the sheath cell via large membranous organelles (see Nervous System - Support Cells; NeuroFIG 24D) (Perkins et al., 1986). This material contains glycoproteins that can leak out of the amphid opening to coat the head of the animal in a thin glycocalyx.\n\n 4.5 Uterine Wall", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 528, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ae36e5bf-2547-4b87-91fa-d468120f2a87": {"__data__": {"id_": "ae36e5bf-2547-4b87-91fa-d468120f2a87", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 4.5) Uterine Wall](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fe5c06ee-2bd7-48f2-8d9c-14c47f6c1f62", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 4.5) Uterine Wall](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "hash": "d75fda3a1bb352f30ca65149b2d1266faf0351c543d54afb018ce810e7053a29", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "A distinctive thick layer coats the inner surface of the uterus, facing the lumen. The luminal uterine membrane is characterized by highly irregular bends that may help create separate microenvironments around developing embryos. The glycocalyx may help to support these irregularities or act to repel bacterial invasion entering through the vulva. Some mutants affecting glycosylation have been shown to block normal egg-laying (Minniti et al., 2004).\n\n 4.6 Fertilization Membrane", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 481, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ab1089b4-7044-4da8-82b3-fbe4d2a04b08": {"__data__": {"id_": "ab1089b4-7044-4da8-82b3-fbe4d2a04b08", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 4.6) Fertilization Membrane](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7eb114bb-9fdd-406f-ab6f-08de8a483b38", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 4.6) Fertilization Membrane](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "hash": "44bf80bb9ed352dea0484b205f46fad82c0a7d8e8089fe87d6225929fcb87281", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Immediately after fusion of an oocyte and a spermatozoon within the spermatheca, the diploid cell displays a new covering, perhaps combining elements from the zona pellucida with exocytosis from intracellular stores of glycoprotein from the oocyte (PeriFIG 5) (Weidman et al., 1985). Although the presence of cortical granules within the oocyte have still not been shown in C. elegans (a possible source for this material), TEM evidence for an intact fertilization membrane has been obtained by high pressure freeze fixations of normal hermaphrodite adults (Hall and Greenstein, unpublished). This glycocalyx is also quickly removed, probably within a few minutes, as the new embryo begins to produce an eggshell underneath it. The glycocalyx breaks away into the uterine lumen and is probably dissolved or expelled from the lumen during egg-laying. Rapid production of a fertilization membrane can offer a physical block  to fertilization by more than one sperm until the eggshell is in place.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 994, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d9b7aede-8747-49e0-8727-692be2ee158f": {"__data__": {"id_": "d9b7aede-8747-49e0-8727-692be2ee158f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 5) Eggshell and Perivitelline Space](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "12e9ac09-029c-4402-aa13-ceb2b9b20829", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 5) Eggshell and Perivitelline Space](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "hash": "8ef26725b906048e24972114f01c49111b1b4611a52cc08918605f89520623f2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Shortly after oocyte maturation and fertilization, a chitinous eggshell is assembled around the embryo and persists until hatching. The eggshell provides an osmotic barrier and a mechanical support that helps the embryo to resist desiccation or predation until the worm is ready to hatch, while still allowing gas exchange for respiration (Schierenberg and Junkersdorf, 1992). Before the two-cell stage, presence of an eggshell is essential for proper development (Zhang et al, 2005). The eggshell has three layers in C. elegans: an outer vitelline layer, a middle chitin-containing layer, and an inner lipid-rich layer (PeriFIG5) (Bird and Bird, 1991; Rappleye et al., 1999; Johnston et al., 2006). Other nematode species can have eggshells with up to five layers.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 765, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3cfe87b5-6d82-4bcc-8d64-e0d16eebddd7": {"__data__": {"id_": "3cfe87b5-6d82-4bcc-8d64-e0d16eebddd7", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 5) Eggshell and Perivitelline Space](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "301fd16e-c933-49c8-a85d-2788eb682873", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 5) Eggshell and Perivitelline Space](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "hash": "8c0248aa7a754f9a196d315ad4c2c420a947a987856314d282592fd379a2b251", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Activation of eggshell deposition is triggered in the oocyte even if the spermatocyte lacks a nucleus (Sadler and Shakes, 2000). After sperm penetration and after the fertilization membrane is shed, the egg\u00e2\u0080\u0099s plasma membrane is thought to separate from the cytoplasm to become the thickened vitelline layer (Johnston et al., 2006). The space underlying the vitelline layer becomes filled with chitin (an N-acetyl-D-glucoseamine homopolymer) and chitin-binding proteins, forming the middle layer of the eggshell (Veronico et al 2001; Berninsone, 2006). Concomitant with middle-layer formation, embryonic cytoplasmic refringent granules are extruded to form the inner proteolipid permeability barrier layer, commonly called the lipid layer. Shortly after forming, the eggshell itself separates from the newly formed plasma membrane of the embryo to form a clear zone called the perivitelline space. This space contains the perivitelline fluid in later-stage embryos. Depending on the fixation technique, the lipid layer may appear to remain as part of the eggshell proper (high-pressure freeze fixation) or may form a deposit held against the embryonic plasma membrane, beneath the perivitelline space (laser-hole chemical fixation). In some mutants (as in pod-1), the lipid layer seems to split to occupy both locales (Rappleye et al., 1999).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1343, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9bfe3377-7322-4e14-8618-fdb0e805902e": {"__data__": {"id_": "9bfe3377-7322-4e14-8618-fdb0e805902e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 6) Embryonic Sheath](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7ca25073-8365-401a-96ed-f7d3d4aaa4b7", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pericellular Structures, Section 6) Embryonic Sheath](https://www.wormatlas.org/hermaphrodite/pericellular/Periframeset.html)"}, "hash": "db5d73a1508864e9180d14720e8a53d19815dc3b2cd48d8a7299cd7d4625784d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The embryonic sheath is secreted over the surface of the embryo by the hypodermis prior to elongation and is connected to the hypodermis directly above the circumferential actin bundles (Priess and Hirsh, 1986; Gatewood and Bucher, 1997). This extracellular layer is suggested to function in transmitting the stress of elongation longitudinally and/or sustaining the internal pressure during elongation. Trypsin treatment and digestion of embryonic sheath results in embryos with improper or arrested elongation. At the three-fold stage, the cuticle assumes the function of maintaining the animal\u00e2\u0080\u0099s morphology.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 612, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "afb90201-ffef-4e26-a800-1f4d63ec9ed7": {"__data__": {"id_": "afb90201-ffef-4e26-a800-1f4d63ec9ed7", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 1) General Description](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f507161e-b65c-4128-9094-68bd41737ca6", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 1) General Description](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "hash": "f7947093b90505c9b4a97b393bd2c31a1ab776bea0806e40a41dc4da49dff65b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The egg-laying apparatus consists of the uterus, the uterine muscles, the vulva, the vulval muscles, and a local neuropil formed by the egg-laying neurons (EggFIG 1). After fertilization, embryos pass from the spermatheca to the uterus, an epithelial egg chamber that links the two arms of the gonad. There, eggs develop to the approximately 30-cell stage (roughly 2.5 hr post-fertilization at 20\u00c2\u00b0C) before being expelled into the environment via the vulva, a passageway from the uterus to the ventral exterior. Under optimal conditions, an adult hermaphrodite will lay 4-10 eggs/hour. Egg-laying is facilitated by contraction of the sex muscles: the vulval muscles, which attach to the lips of the vulva, and the uterine muscles, which encircle the uterus. Muscle activity is regulated by motor neurons, in particular motor neurons VCn (VC1-6) and HSNL/R, which synapse onto each other and onto vulval muscle arms, forming a neuropil near the vulva. Tissues comprising the egg-laying apparatus arise from several different lineages (see ReproTABLE 1). As described below, the developing gonad and vulva act as organizing centers, recruiting cells from other regions to the midbody, coordinating cell patterning between different tissues, and directing axon guidance and synaptic patterning of the neurons.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1307, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a359d88b-dcf4-4018-a5e3-53b4ad900f93": {"__data__": {"id_": "a359d88b-dcf4-4018-a5e3-53b4ad900f93", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 2) The Uterus](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f090268f-37de-4c01-a77f-bf058a0f7142", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 2) The Uterus](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "hash": "c347e1fcab951e66a20e2ee5b1ae64f89d113fba745c9702999f92287d0cfedc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The uterus consists of an anterior and posterior lobe joined to a  central chamber. The central chamber is joined ventrally to the vulval  epithelial tube (EggFIG 2A,B and EggFIG 3A). The entire outer (basal) surface of the uterus is covered by a thin basal lamina called the uterine basal lamina (UBL) (EggFIG 3B; see also EggFIG 11C). The organization of cells that comprise the uterus is most readily apparent during the late-L4 stage, after uterine and vulval morphogenesis have taken place but before the onset of ovulation, after which the uterus becomes distorted and crowded with embryos. The anterior and posterior uterus lobes are each composed of four uterine toroid epithelial syncytia: ut1, ut2, ut3 and ut4 (EggFIG 2A,B; EggTABLE 1). ut1\u00e2\u0080\u0093ut4 are joined to one another and to their neighbors both by adherens junctions (EggFIG 2C) and by pleated septate junctions, most robust between ut4 and ut3 and less obvious at the other borders. Cytoskeletal elements are sometimes evident in ut toroids, running circumferentially, suggesting that the toroids may have myoepithelial properties (Newman et al., 1996).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1121, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "88976ad0-5e68-46c4-b973-8f7520e50577": {"__data__": {"id_": "88976ad0-5e68-46c4-b973-8f7520e50577", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 2) The Uterus](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9cdf194e-ce8f-45b1-88c3-a789c7dba589", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 2) The Uterus](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "hash": "39fd401df8804b1d2ea368a8648f431e629b90ca46ba8b0cdb962737dddf03e4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The central chamber of the uterus is capped dorsally by the dorsal uterine (du) syncytium and ventrally by the uterine seam (utse) syncytium and uterine ventral (uv) cells uv1\u00e2\u0080\u00933 (EggFIG 2A,B and EggFIG 3A,B; EggTABLE 1). uv1\u00e2\u0080\u0093uv3 form a multilayered set of flaps, binding the ventral uterus to the dorsalmost ring of the vulva, vulF. The utse has a distinctive H-shaped structure. The two sides of the H attach to the lateral seam of the animal and hold the uterus in place. At the join, the basal lamina is thickened and contains hemicentin (EggFIG 3B) (Vogel and Hedgecock, 2001). The central portion of the utse (the crossbar of the H) initially forms a hymen membrane between uterine and vulval lumens. Passage of the first egg breaks this membrane and the two lumens become continuous.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 793, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "594147d8-50df-41d2-a837-092888ad59dc": {"__data__": {"id_": "594147d8-50df-41d2-a837-092888ad59dc", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 2) The Uterus](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "58d1373c-a3ef-4018-ae79-3bf882d21393", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 2) The Uterus](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "hash": "09897fe4caf490f384941bde53fba0d90c53aa39ecfe2833e5553a99c53f344e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Before the first fertilization event, the lumen of the uterus is narrow and blocked by a series of inwardly projecting fingers that extend from the uterine lumen wall (see EggFIG 5B and EggFIG 11B below). After passage of the first egg, the mature uterus retains a few inward septa that may derive from these earlier fingers. Both the developing and the mature uterine lumen have a continuous thickening or electron-dense layer (possibly a glycocalyx or surface coat; see EggFIG 11C). This is also apparent on the lumenal (apical) membrane, lining projecting fingers, and septa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 578, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "675effe7-0354-49ee-916b-8991a31e61ed": {"__data__": {"id_": "675effe7-0354-49ee-916b-8991a31e61ed", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 2) The Uterus](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9c871b0e-b9d8-4b6b-a31c-68c055228555", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 2) The Uterus](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "hash": "de8b9f312b8722c4bcc42a97d522f0e9a77c8ce3d512d592ccc6dcd7b301d009", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Cells of the uterus arise from dorsal uterine (DU) and ventral uterine (VU) blast cells of the larval SPh (Reproductive System - Somatic Gonad; EggFIG 4A; EggTABLE 1) (Kimble and Hirsh, 1979; Newman et al., 1996). In late L2, one of two somatic gonadal cells, Z1ppp or Z4aaa, is specified to become the anchor cell (AC), whereas the other becomes one of three VU blast cells (EggFIG 4A) (Kimble, 1981; Greenwald et al., 1983; Seydoux and Greenwald, 1989; Greenwald, 1997; Karp and Greenwald, 2003).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 498, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "64870668-99a0-487f-8434-8cb3f81c9f22": {"__data__": {"id_": "64870668-99a0-487f-8434-8cb3f81c9f22", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 2) The Uterus](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "aeccc27f-93ea-4b8d-8b90-77a04008d69c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 2) The Uterus](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "hash": "76c7f3714bbb94d8c6fc1e662246163761bf1aa7e552a36f98a3eefcbc699774", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In late L3, the AC induces VU granddaughters to adopt the \u00cf\u0080 fate (EggFIG 4B and EggFIG 5A). \u00cf\u0080 daughters subsequently differentiate into uv1 and utse cells of the ventral uterus, which lie immediately dorsal of the developing vulva (EggFIG 4C,D and EggFIG 5B,C) (Newman et al., 1995, 1996; Chang et al., 1999). The differentiation of these and many other terminal uterine cells involves dramatic changes in shape and/or fusion to achieve their final  morphology (Newman et al., 1996). As described below, the AC also patterns cells of the vulva. This dual induction of vulval and uterine cell fates by the AC ensures that cells forming the physical connection between the uterus and vulva (utse, uv1, and vulF) develop in physical register. The AC also contributes to formation of this connection by creating an opening at the apex of the vulva.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 846, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ac4fad3b-90c6-4264-a927-970b5134a71d": {"__data__": {"id_": "ac4fad3b-90c6-4264-a927-970b5134a71d", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 3) The Vulva](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a272188b-0e54-4554-a5e4-1c803aa3e78e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 3) The Vulva](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "hash": "9a25cbb156abee70369d9c6413619146bb4ead1ab45454159834037593b4c4ac", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The vulva (EggFIG 6A) is formed from a stack of seven nonequivalent epithelial toroids or rings: (in ventral-to-dorsal order) vulA, vulB1, vulB2, vulC, vulD, vulE, and vulF (EggFIG 3A). Each ring is either a single tetranucleate syncytium or two binucleate half-ring syncytia (vulB1 and vulB2). The vulval lumen is lined with cuticle. As described below, the toroids are formed by vulval cells of two fates: primary fate (vulE and vulF) or secondary fate (vulA\u00e2\u0080\u0093D). These cells and the toroids they form express distinct combinations of genes (Inoue et al., 2002) and, potentially, different characteristics and properties. For example, during copulation, males locate the vulva with their hook and post-cloacal sensilla, possibly in response to signals or characteristics associated specifically with toroids formed by secondary-fated cells (M. Barr, pers. comm.).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 866, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f7ec75a4-d6fd-43e5-a167-66b1a6f5a131": {"__data__": {"id_": "f7ec75a4-d6fd-43e5-a167-66b1a6f5a131", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 3) The Vulva](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ffe5ad7b-204e-4d93-a691-d0db57c547f8", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 3) The Vulva](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "hash": "126ac0cac450a0788a09e05d3457e423ae187c3932c1857efa7016bae97507e8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Adjacent toroids are joined to their neighbors via adherens junctions (EggFIG 6E). The dorsalmost toroid vulF is also linked by adherens junctions to the uterine transitional epithelial cells uv1 and uv2 and possibly to the utse (EggFIG 3A). The ventralmost toroid vulA is linked via adherens junctions to the ventral hypodermal ridge. The vulE toroid stretches laterally and is linked on its basal (outer) surface to the body wall at the lateral seam by a specialized thickened basal lamina (EggFIG 3A,B).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 506, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5f4edd66-76f0-4cdb-a05e-b438130d330a": {"__data__": {"id_": "5f4edd66-76f0-4cdb-a05e-b438130d330a", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 3) The Vulva](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "03558461-c3c1-486f-bd6d-8f69a37def2e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 3) The Vulva](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "hash": "a7e6e71e4f37ff2ac180af6c63bc7e6eb4f80685dc74ec0724623df08e80b8cb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Vulval development spans roughly the same period as uterine development: L3 to late L4. For a summary figure of the stages of vulval development, please see EggFIG Sup1. Establishment of the vulva requires the local deformation of existing ventral structures such as the ventral nerve cord (VNC) (EggFIG 1) and ventral body wall muscles (EggFIG 3A), which are deflected laterally in this region to accommodate the vulva.  Vulval development can be divided into two phases: (1) vulval cell patterning and generation (EggFIG 7 and EggFIG 8) and (2) vulval morphogenesis (EggFIG 9). The molecular and genetic mechanisms underlying these processes, particularly cell patterning, have been studied extensively and are described in the following reviews and papers and references therein (Greenwald, 1997; Kim, 1997; Eisenmann et al., 1998; Levitan and Greenwald, 1998; Hanna-Rose and Han, 2000; Shemer and Podbilewicz, 2003; Ceol and Horvitz, 2004; Sundaram, 2004).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 960, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0069fe44-ab1a-4120-8d3b-ca671e388145": {"__data__": {"id_": "0069fe44-ab1a-4120-8d3b-ca671e388145", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 3.1) Vulval Cell Patterning](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "52913523-9403-4e0e-a251-14210f9b10b9", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 3.1) Vulval Cell Patterning](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "hash": "e7ea32ad4928a7ab77d74f6b156c9d717fbd80c7d102b0335caebfe6d76a9869", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The cells that form the vulval toroids are the progeny of ventral hypodermal Pnp cells (EggFIG 7B) (Sulston and Horvitz, 1977). Twelve Pnp cells are born mid-L1. The six central cells P3p\u00e2\u0080\u0093P8p are endowed with equal potential to produce vulval cell lineages and are referred to as vulval precursor cells (VPCs) (EggFIG7A and EggFIG 8A). In L3, the VPCs are patterned so that vulval potential is restricted to the central three cells P5p\u00e2\u0080\u0093P7p. This patterning of the VPCs involves the combined action of three intercellular signaling events: an inductive signal emanating from the AC (LIN-3/LET-23 MAPK pathway activation), lateral signaling between VPCs (LIN-12/Notch), and signals from hyp 7 (reviewed in Greenwald, 1997; Sundaram, 2004; Sternberg, 2005).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 758, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9fcbcaed-2d7a-402c-8b0f-606223d8d8ac": {"__data__": {"id_": "9fcbcaed-2d7a-402c-8b0f-606223d8d8ac", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 3.2) Vulval Morphogenesis](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "38de8250-6b8e-46e4-b87e-75f5f3e94c66", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 3.2) Vulval Morphogenesis](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "hash": "064bf19cbbed71926a301de6a2fc14e551b49b229b6cad73a305885aadf51f49", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "During the final round of vulval cell divisions, the primary descendants and some secondary descendants detach from the cuticle, allowing the vulval sheet to bend inward and the cells within it to rearrange their cell\u00e2\u0080\u0093cell contacts (EggFIG 8D). This invagination step establishes the beginnings of the vulval lumen, which continues to expand during morphogenesis. Proteoglycans and their associated glycosaminoglycans, likely expressed in vulval cells, are necessary for this step, although their precise role is not known (Herman and Horvitz, 1999; Bulik et al., 2000; Hwang et al., 2003). As morphogenesis continues, cells migrate toward the center of the developing vulval primordium and wrap around to meet their anterior/posterior homologs on the other side (EggFIG 9) (Sharma-Kishore et al., 1999). Homotypic cell fusions occur between cells of homologous fate, resulting in the formation of toroid or half-toroid rings (see Inoue et al., 2002 for a useful guide to vulval cell nuclei positions during and after morphogenesis).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1035, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0c127e07-d1ff-4eb7-a82e-fe5393282664": {"__data__": {"id_": "0c127e07-d1ff-4eb7-a82e-fe5393282664", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 3.2) Vulval Morphogenesis](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f8bc88dd-2e52-4193-bcd4-99f958128f9a", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 3.2) Vulval Morphogenesis](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "hash": "b9c7c054428eacdd540e57e953cc5662b65bc7259156189c8b04d09d8c98ae4e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "As part of the process of joining vulval and uterine lumens, the AC creates a hole in the apex of the developing vulva (EggFIG 8). In L3, while Pnp cells are dividing, the ventral hypodermal basal lamina and gonadal basal lamina break down precisely at the site of contact with the AC. The basolateral portion of the AC crosses through this gap, attaches to, then inserts between the descendants of the primary-fated P6p lineage cells. This invasion is stimulated by a diffusible signal from the primary cells (Sherwood and Sternberg, 2003). Later, P6p terminal progeny fuse, forming a toroid (vulF) around the invading AC process. The AC is then removed by heterotypic fusion with the utse, leaving a channel in the apex of the vulva (Newman et al., 1996). When the utse membrane is ruptured by passage of the first egg, uterine and vulval lumens become continuous. \n\nDuring late L4, the vulval muscles attach to the vulval epithelial tube and to the body wall (see below). The tube then partially everts (turns inside out), generating the adult vulva in which the lumen is closed until vulval muscles contract (EggFIG 10) (Sulston and Horvitz, 1977; Sharma-Kishore et al., 1999).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1181, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "de447c74-06dd-4883-804f-3730127d23d9": {"__data__": {"id_": "de447c74-06dd-4883-804f-3730127d23d9", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 4) Uterine and Vulval Muscles](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "952edae8-33b2-41d4-a4fb-fec4ae0adb0d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 4) Uterine and Vulval Muscles](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "hash": "d5560e2626a4cefc7fab23440a182e09c6e0b8ac0e623cf072ba7c1eef3bff5c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The uterine (um1L/R, um2L/R) and vulval (vm1L/R, vm2L/R) muscles (EggFIG 1 and EggFIG 11A), collectively referred to as the sex muscles, are required for moving eggs through the uterus and vulva. Only 4 the 16 sex muscles receive direct inputs from the egg-laying neurons. The remaining sex muscles are electrically coupled, either directly or indirectly, to these innervated muscles (see EggFIG 13). This configuration may serve to coordinate uterine and vulval contraction. The sex muscles are classified as nonstriated muscles because they do not have the striated appearance (typified by body wall muscle) normally attributed to the presence of an ordered array of multiple sarcomeres (muscle contractile units; see Muscle System - Somatic Muscle). Vulval muscles have a single sarcomere that extends along the entire muscle length and attaches to a discrete zone in the body wall at one end and to the vulva at the other end (White, 1988). The uterine muscle myofilament network seems to be anchored to a thin basal lamina on the surface facing the uterus. In contrast to the vulval muscles, the attachment points are randomly arrayed and this distribution of dense bodies is similar to that seen in vertebrate smooth muscles (see Muscle System - Nonstriated).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1265, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b3b0f693-c02b-4372-b7de-55cb0dc38f0c": {"__data__": {"id_": "b3b0f693-c02b-4372-b7de-55cb0dc38f0c", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 4) Uterine and Vulval Muscles](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cff81578-c0ba-456d-8ce6-eed5bc8d9c2b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 4) Uterine and Vulval Muscles](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "hash": "7800d6e2394e361e851a1d0857aca2e1e6904808dc5a9b92bc2714c70c1bad2a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Eight uterine muscles are arranged in four bands around the uterus lobes: two bands per lobe, two muscle cells per band (EggFIG 1). A left/right pair of um2-type muscles (um2L/R) encircles the more distal ut toroids of each lobe. A left/right pair of um1-type muscles (um1L/R) cup the ventral half of the uterus over the more proximal ut toroids, and at their dorsal edges, they attach to the lateral seam. The ventral-proximal edges of the um2 muscles overlap with the um1 muscles (EggFIG 1). Uterine muscles are covered in a thin basal lamina (EggFIG 11C). The muscle filaments are circumferentially oriented so their contraction potentially moves eggs by squeezing on the uterus (EggFIG 11C) (Sulston and Horvitz, 1977). The uterine muscles are not directly innervated and are instead coupled via gap junctions, either directly or indirectly, to vulval muscles that are innervated by the egg-laying neurons (see EggFIG 13) (White et al., 1986) (see also Gap Junctions).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 972, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "26630ebd-4876-437b-801f-b1ad2cad20b8": {"__data__": {"id_": "26630ebd-4876-437b-801f-b1ad2cad20b8", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 4) Uterine and Vulval Muscles](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "85a41df6-767d-49c0-99b4-ddbb2accbe41", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 4) Uterine and Vulval Muscles](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "hash": "6bb843b312494911aa01034754062ec2acb23eb38440a00a00b0059785666443", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The vm2 muscles attach between the uterus and vulF (EggFIG 12B). Their distal ends insinuate between adjacent members of the ventral body wall muscle quadrant (EggFIG 11B). vm1 muscles attach to the vulva more ventrally than do the vm2s, between vulC and vulD toroids (EggFIG 12B), but they join the body wall more dorsally, attaching near the dorsal edge of the ventral body wall muscle quadrant (EggFIG 11B).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 410, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "747f4682-f8ee-45e2-93b5-4a90f5372fb1": {"__data__": {"id_": "747f4682-f8ee-45e2-93b5-4a90f5372fb1", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 4) Uterine and Vulval Muscles](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0e0967ca-94d5-4cb3-ad17-d107fa882c3f", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 4) Uterine and Vulval Muscles](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "hash": "9ce13895b1e93a094728ebeed3491f54636ea0d3ed1bae9023180759d9f4e383", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The vm2s are the only sex muscles that are directly innervated (EggFIG 13) (White et al., 1986). The muscles extend arms into the regions of neuropil formed at the vulva where they receive synaptic inputs (see EggFIG 15A, B&C). vm1 connects to vm2 by gap junctions. Coordinated foreshortening of the vulval muscles pulls the lips apart, allowing eggs to pass through the lumen and out into the environment.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 406, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fd79fb49-efde-4273-80d0-b707101a3382": {"__data__": {"id_": "fd79fb49-efde-4273-80d0-b707101a3382", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 4) Uterine and Vulval Muscles](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2b719bbc-f7e0-45f0-8bcf-616bfbb7fed4", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 4) Uterine and Vulval Muscles](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "hash": "f55a260d7c573485233cb464ec54e824c00ccc89c3a172872509bff7d8b573c2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Uterine and vulval muscles derive from a common precursor, the sex myoblast (SM). During L1, the mesoderm (M) blast cell (EggFIG 14A,B) lineage produces a left and a right SM (SML/R) (Sulston and Horvitz, 1977). In L2, SML/R migrate anteriorly along ventral muscle quadrants to the precise center of the developing gonad and future vulva (EggFIG14C). There, the SMs undergo three rounds of division to produce the vulval and uterine muscle cells (EggFIG 14D) which then attach to the everted vulva (EggFIG 14E) (for details on muscle specification programs, see Harfe et al., 1998; Corsi et al., 2000; Lui and Fire, 2000; Kosta and Fire, 2001; Eimer et al., 2002).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 664, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d2a66677-a2aa-40f8-8260-6850098a4ccb": {"__data__": {"id_": "d2a66677-a2aa-40f8-8260-6850098a4ccb", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 4) Uterine and Vulval Muscles](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5416289e-019d-47c7-9851-538361895ceb", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 4) Uterine and Vulval Muscles](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "hash": "5a665f5ab1d575124ac869a6ef66683b84d7fd3c7daffb7599f5d14c0418e036", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "SM migration and positioning at the gonad center is guided by the balance of several forces: a gonad-dependent attractive (GDA) mechanism  (Thomas et al., 1990), a gonad-dependent repulsive (GDR) mechanism (Stern and Horvitz, 1991), and a gonad-independent attractive (GIA) mechanism (Chen et al., 1997; Huang et al., 2003). The DUs, VUs, and AC of the SPh (EggFIG 14A) and primary-fated P6p vulval cells (EggFIG 7A) express FGF-related ligand EGL-17, which is likely to correspond to the GDA signal for SM migration. Interestingly, these same cells also appear to be the source of the GDR mechanism (Burdine et al., 1997, 1998; Branda and Stern, 2000).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 653, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "608ddcbe-7cdc-4d27-bcfa-9418bfa8668c": {"__data__": {"id_": "608ddcbe-7cdc-4d27-bcfa-9418bfa8668c", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 5) Egg-laying Neurons](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2ec5c4fa-fb5c-42b1-b39b-f9dce117ea40", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 5) Egg-laying Neurons](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "hash": "4b7e631da50d2d19cebfe2d316525a7a43d0f1d8119b496e3332ac6ba7fb99e7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The vm2 muscles receive major inputs from two groups of motor neurons, the VCn neurons (VC1\u00e2\u0080\u00936) and the HSNs (HSNL/R) (EggFIG 15A) (see White et al., 1986 and Neuron system for detailed descriptions of each neuron). The precise role of each neuron and the neurotransmitters they release in egg-laying appears to be complex; several models have been proposed (Weinschenker et al., 1995; Waggoner et al., 1998, 2000; Bany et al., 2003; Shyn et al., 2003).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 454, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "40846028-b5b2-490c-bac6-187565255e94": {"__data__": {"id_": "40846028-b5b2-490c-bac6-187565255e94", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 5) Egg-laying Neurons](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a38ed70f-9e88-44cd-ab19-50b7261ea001", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 5) Egg-laying Neurons](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "hash": "67ad887b0b79125c4791698b6afd899bc7523edcbed3ca59496b4b50dd1826fd", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "VC4 and VC5 cell bodies flank the vulval epithelial tube and have short processes in the VNC. VC1, VC2, VC3, and VC6 neuron cell bodies are spaced along the length of the VNC. Each sends out a single main axon that runs in the dorsal \u00e2\u0080\u009cneighborhood\u00e2\u0080\u009d of the cord and makes similar synaptic contacts to one another. When VCn neuron axons reach the vicinity of the vulva, they send processes dorsally along the ventral basal (outer) surface of vulE (EggFIG 16). The neurons branch and synapse with one another and with the HSNs and vm2 muscle arms, forming a local neuropil (EggFIG 15B). VC4 and VC5 branch more extensively than other VC neurons in this region.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 661, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c96c9bb1-05a2-4472-a6e7-381745838cb1": {"__data__": {"id_": "c96c9bb1-05a2-4472-a6e7-381745838cb1", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 5) Egg-laying Neurons](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "78dc130a-88a5-4e55-8a8b-dafbbee91419", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 5) Egg-laying Neurons](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "hash": "4c232574453d08f527817810e4ff90bde8cedc026c8a8661142681a408ca1e91", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The VCn neurons are derived from the anterior daughters of ventral hypodermal blast cells P3\u00e2\u0080\u0093P8, the same cells that produce VPCs (described above; see Sulston and Horvitz, 1977). The VCn neurons are born in L1, begin to send out processes in late L3, and branch in the region of the vulva during L4 (EggFIG 14A). Surprisingly, VCn branching depends on cells of the vulva and not on the presence of their targets (Li and Chalfie, 1990; Colavita and Tessier-Lavigne, 2003).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 474, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b4b74ee0-c654-4014-a13e-228dbcfda281": {"__data__": {"id_": "b4b74ee0-c654-4014-a13e-228dbcfda281", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 5) Egg-laying Neurons](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c9551309-b622-4e83-be3b-d9910ac23f33", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 5) Egg-laying Neurons](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "hash": "209e8b0817ef60b884bebe021e8a877b6ed0d67b634fbab219a7f11e1479d5a9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "HSNL/R cell bodies are situated subventrally, just posterior to the vulva (EggFIG 15B). Each HSN axon projects ventrally to the midline to join the ipsilateral VNC (VNCR or VNCL) and from there extends into the nerve ring. As they pass the vulva, the HSNs defasciculate dorsally, branch, and form synapses with VCn neurons and vm2 muscle arms, thereby contributing to the neuropil.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 381, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1a87ece1-1d43-45ec-92da-cc4d694f28d5": {"__data__": {"id_": "1a87ece1-1d43-45ec-92da-cc4d694f28d5", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 6) List of Cells in the Uterus and Vulva](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "826e0868-b295-43c6-a5e3-d3d63782d92a", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 6) List of Cells in the Uterus and Vulva](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "hash": "a17e2d04032e6e62894d5b82eec23613ec89608f6d0338eb80d51c52e7431f62", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "1. Late L2/early L3 stage SPh cells that give rise to the uterus DU, Z1.pap (Dorsal Uterine precursor; generates uterus, spermatheca and spermatheca-uterine valve cells)\n\n\n\nVUs and AC are of either the 5R or 5L configuration: 5R configuration VU, Z1.ppa (Ventral Uterine precursor; generates uterus, spermatheca and spermatheca-uterine valve cells) \n\nAC, Z1.ppp (Anchor Cell) \n\nVU, Z4.aaa (Ventral Uterine precursor; generates uterus, spermatheca and spermatheca-uterine valve cells) \n\nVU, Z4.aap (Ventral Uterine precursor; generates uterus, spermatheca and spermatheca-uterine valve cells)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 591, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "59787801-961c-49eb-9a3c-4ed1f4af05b3": {"__data__": {"id_": "59787801-961c-49eb-9a3c-4ed1f4af05b3", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 6) List of Cells in the Uterus and Vulva](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "585b0a61-6bd6-42d0-9fa9-e82f0d112024", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 6) List of Cells in the Uterus and Vulva](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "hash": "ed9f49838883f3e8e7cf30dee018432c116154eb6188ec0cc2552990dbcef051", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "5L configuration VU, Z1.ppa (Ventral Uterine precursor; generates uterus, spermatheca and spermatheca-uterine valve cells) \n\nVU, Z1.ppp (Ventral Uterine precursor; generates uterus, spermatheca and spermatheca-uterine valve cells) \n\nAC, Z4.aaa (Anchor Cell) \n\nVU, Z4.aap (Ventral Uterine precursor; generates uterus, spermatheca and spermatheca-uterine valve cells) \n\nDU, Z4.apa (Dorsal Uterine precursor; generates uterus, spermatheca and spermatheca-uterine valve cells)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 472, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2ec24949-ae98-443c-8ba1-7d21c9ce674c": {"__data__": {"id_": "2ec24949-ae98-443c-8ba1-7d21c9ce674c", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 6) List of Cells in the Uterus and Vulva](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4ae42a4c-abe9-4612-9f43-63cacb0119dd", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 6) List of Cells in the Uterus and Vulva](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "hash": "4ad7248d22637280a0092663c3c8a30290e0f7099b8da87672849e30a7db1b1c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "2. L3 stage intermediate blast cells of the uterus", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 50, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a82b740b-73ee-4a00-b8c1-22fc234fbe45": {"__data__": {"id_": "a82b740b-73ee-4a00-b8c1-22fc234fbe45", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 6) List of Cells in the Uterus and Vulva](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "49b2d8db-9a16-4ea8-aff2-6aa5c4568b83", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 6) List of Cells in the Uterus and Vulva](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "hash": "e565fcba7bedf3ee660b72eac3c5981a776ff29830aee2b6161abbca4cf023ce", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The Dorsal Eight (DE) cells (great-grand progeny of the DUs) DE1, Z1.papaaa\u00a0(generates anterior arm sp cells)\n\nDE2, Z1.papaap\u00a0(generates anterior arm sp and sujc valve cells)\n\nDE3, Z1.papapa\u00a0(generates anterior arm sujn valve cells and ut2-4 uterus cells)\n\nDE4, Z1.papapp\u00a0(generates uv3, uv2, ut1, du)\n\nDE5, Z1.pappaa\u00a0(generates du, ut1, uv2, uv3)\n\nDE6, Z1.pappap\u00a0(generates ut2-4 and posterior arm sujn valve)\n\nDE7, Z1.papppa\u00a0(generates posterior arm sujc valve and sp)\n\nDE8, Z1.papppp\u00a0(generates posterior arm sp)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 515, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2fa6821d-f302-48c8-91c6-2b51b2d2b82e": {"__data__": {"id_": "2fa6821d-f302-48c8-91c6-2b51b2d2b82e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 6) List of Cells in the Uterus and Vulva](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b9553016-a107-47fb-84af-9cdd7108c686", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 6) List of Cells in the Uterus and Vulva](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "hash": "ff01db5824c70a3fc4dd5316fac900f23f5888d6e864c66a49d6b81922c24511", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "DE1, Z4.apaaaa\u00a0(generates anterior arm sp)\n\n DE2, Z4.apaaap\u00a0(generates anterior arm sujc valve and sp) WB says male gon sv group\n\n DE3, Z4.apaapa\u00a0(generates anterior arm sujn valve cells and ut2-4 uterus cells)\n\n DE4, Z4.apaapp\u00a0(generates uv3, uv2, ut1, du)\n\n DE5, Z4.apapaa\u00a0(generates du, ut1, uv2, uv3)\n\n DE6, Z4.apapap\u00a0(generates ut2-4 and posterior arm sujn valve)\n\n DE7, Z4.apappa\u00a0(generates posterior arm sujc valve and sp)\n\n DE8, Z4.apappp\u00a0(generates posterior arm sp)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 475, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5384f2c9-ad05-4071-8238-af732a1aa847": {"__data__": {"id_": "5384f2c9-ad05-4071-8238-af732a1aa847", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 6) List of Cells in the Uterus and Vulva](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "01c1f3ad-2a4c-4f26-a56e-368d920148da", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 6) List of Cells in the Uterus and Vulva](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "hash": "d2e248b61893fdd1fab2d7e6ad0c7e1d8accf959851063058311ee3d911e0565", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "3. Adult uterus ut1 - anterior (5L, 5R), posterior (5L, 5R)\n\nut2 - anterior (5L, 5R), posterior (5L, 5R)\n\nut3 - anterior (5L, 5R), posterior (5L, 5R)\n\nut4 - anterior (5L, 5R), posterior (5L, 5R)\n\ndu\n\nutse - 5L, 5R\n\nuv1\n\nuv2\n\nuv3", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 228, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "70cbbfb9-7e96-461d-8deb-dd71958612d3": {"__data__": {"id_": "70cbbfb9-7e96-461d-8deb-dd71958612d3", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 6) List of Cells in the Uterus and Vulva](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9002adf1-c71f-472d-935a-a6f6ddb897ad", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 6) List of Cells in the Uterus and Vulva](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "hash": "61253fdbdfeaac92c789cd49bd2c16c90710c8222dc352508d0d1280af3234e3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "4. L3 stage Vulva Precursor Cells (VPCs) P3.p\n\nP4.p\n\nP5.p\n\nP6.p\n\nP7.p\n\nP8.p", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 75, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5b8843ed-11f3-4626-8059-0407cafb8d03": {"__data__": {"id_": "5b8843ed-11f3-4626-8059-0407cafb8d03", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 6) List of Cells in the Uterus and Vulva](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e59649c1-faab-456d-b6e7-57cb708bfa88", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 6) List of Cells in the Uterus and Vulva](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "hash": "042ee421ea1899cbf1ec4ad138940048ed1f2a80881fccdd6133d5dee4ca35b3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "5. Adult vulva vulA\n\nvulB1\n\nvulB2\n\nvulC\n\nvulD\n\nvulE\n\nvulF", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 57, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "49c215b6-33e8-4b17-b9b9-ad70684219c8": {"__data__": {"id_": "49c215b6-33e8-4b17-b9b9-ad70684219c8", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 6) List of Cells in the Uterus and Vulva](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5bcc0822-4218-4c61-908f-d28409db3b57", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 6) List of Cells in the Uterus and Vulva](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "hash": "b3625fed15e13b74ffb829f319dee3bfffadde294d90b1b19d4f8189aa813d68", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "6. Uterine and vulval muscles (sex muscles) um1L/R\n\num2L/R\n\nvm1L/R\n\nvm2L/R", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 74, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "41e1a43e-922c-49b7-8dde-3d710730ed9c": {"__data__": {"id_": "41e1a43e-922c-49b7-8dde-3d710730ed9c", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 6) List of Cells in the Uterus and Vulva](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "81015388-f75b-444e-9b11-22193098cbd9", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 6) List of Cells in the Uterus and Vulva](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "hash": "03ebd0c6c00b8c466720fd48ea32ba30376ea9874519b6b86c3167470051ffa4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "7. Egg-laying neurons VCn (VC1-6)\n\nHSNL/R", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 41, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9e6f41b2-c6cd-49b9-84d9-ccae0180dc5d": {"__data__": {"id_": "9e6f41b2-c6cd-49b9-84d9-ccae0180dc5d", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 7) References](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e94359df-7722-4b86-8170-ae255ac9f7e5", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Egg-laying Apparatus, Section 7) References](https://www.wormatlas.org/hermaphrodite/egglaying apparatus/Eggframeset.html)"}, "hash": "46dcbd6c0719429cee2e46eab4cbe0cec8799c6665b1cfd65871982996324ce7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Kimble, J. 1981. Alterations in cell lineage following laser ablation of cells in the somatic gonad of Caenorhabditis elegans. Dev. Biol. 87: 286-300. Abstract", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 159, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c97d1b60-91a7-4ef1-b791-6be607b22ed2": {"__data__": {"id_": "c97d1b60-91a7-4ef1-b791-6be607b22ed2", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Alimentary System, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/alimentary/Alimframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8d47586f-6a35-415b-9594-6bb93617d2c3", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Alimentary System, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/alimentary/Alimframeset.html)"}, "hash": "17da6d2a2eee27d8fd1de53e55f241d7e5ceb60f10f1903ca262ac070db5db16", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The alimentary system, one of the most complex portions of the nematode anatomy, is composed of a large variety of tissues and cell types (White, 1988). Direct intercellular connections between the alimentary tissues and the rest of the body are minimal. Topologically, this system forms a separate epithelial tube running inside the cylindrical body wall, separated from it by the pseudocoelomic space, and placed parallel to the gonad. At the anteriormost end, the pharyngeal epithelium connects to the arcade cells of the lips (See Interfacial Epithelial Cells). The posteriormost region of the alimentary tract, the rectal epithelium and anus, is surrounded by the tail hypodermis and the dorsorectal ganglion. One pair of somatic neurons (RIPL/RIPR) penetrates the pharyngeal basal lamina to make gap junctions with a pair of pharyngeal neurons (I1L/R). Otherwise the only connection that spans the two systems (somatic vs. enteric) are the four specialized enteric muscle cells that act on the intestine and rectal valve while being driven by the somatic motor neurons, AVL and DVB.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1088, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "622d5446-7a35-4390-8854-3f47d686ff42": {"__data__": {"id_": "622d5446-7a35-4390-8854-3f47d686ff42", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Alimentary System, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/alimentary/Alimframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2f1a3b15-f8f2-4e09-adee-cf9c851b208e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Alimentary System, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/alimentary/Alimframeset.html)"}, "hash": "c0762b91a5bfdd4e803ac6971e161e405de05977a3dd11740c8d2ea4600539e2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The alimentary system is divided into the foregut (stomodeum; buccal cavity and the pharynx), the midgut (intestine), and the hindgut (proctodeum; rectum and anus in hermaphrodites and cloaca in males) and  contains a total of 127 cells (AlimFIG 1). The stomodeum and proctodeum are lined with cuticle, which is shed along with body cuticle during molts (See Cuticle) (Bird and Bird, 1991). The stomodeum and proctodeum are also regions into which enteric glands open; pharyngeal glands open to the stomodeum and rectal glands open to the proctodeum. Ingested material flows through the digestive tract by the muscular pumping and peristalsis of the pharynx at the anterior end, and the waste material is discarded through the opening of the anus at the posterior end by the action of the enteric muscles. The intestine itself is devoid of any muscular structure in C. elegans, although its rear portion can be contracted by the stomatointestinal (SI) muscles (see Intestine). During defecation, the body wall muscles also contribute to the control of internal pressure and concentration of the gut contents before the expulsion of the waste material (see Rectum and Anus). Developmentally, the intestine is endodermal in origin, whereas the stomodeum and proctodeum have a mixed lineage from ectodermal and mesodermal origins (Bird and Bird, 1991).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1349, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b57227f5-7fd0-4fdc-9307-4ab72dac00b6": {"__data__": {"id_": "b57227f5-7fd0-4fdc-9307-4ab72dac00b6", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Alimentary System, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/alimentary/Alimframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3e75a25e-c77e-4b94-bcfa-6d87fdde46a2", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Alimentary System, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/alimentary/Alimframeset.html)"}, "hash": "bd8291481fec7aa3ad8be682fcf3fc901bb6c8c38648a0dddb623c2c7314fc17", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The alimentary system is described in different sections by its individual organs along the length of the body, from anterior to posterior (see Pharynx, Intestine and Rectum and Anus sections and also Pharynx Atlas). The tissues that connect to the pharyngeal epithelium and are more anterior to the pharyngeal epithelium within the lips (hyp1, hyp2, hyp3, the lip sensilla, and the arcade cells) are described in the Epithelial System - Hypodermis.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 449, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e2b146e2-7f60-41fa-9d1b-3cfe46138b28": {"__data__": {"id_": "e2b146e2-7f60-41fa-9d1b-3cfe46138b28", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Alimentary System, Section 2) References](https://www.wormatlas.org/hermaphrodite/alimentary/Alimframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "07f0d26e-656b-4a3d-b74e-bad7f372579a", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Alimentary System, Section 2) References](https://www.wormatlas.org/hermaphrodite/alimentary/Alimframeset.html)"}, "hash": "99fc75e4ed120464ca7d4df0ef82c42ae647005599aeb5a03451d84544ccb493", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Fukushige, T., Schroeder, D.F., Allen,  F.L., Goszczynski, B. and McGhee, J.D. 1996. Modulation of gene expression in the embryonic digestive tract of C. elegans. Dev. Biol. 178: 276-288. Abstract", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 196, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7eb5082c-44ae-4e40-952c-87e333da5f2f": {"__data__": {"id_": "7eb5082c-44ae-4e40-952c-87e333da5f2f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 1) Caenorhabditis elegans as a Genetic Organism](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d206d0ba-f6c2-4201-b718-59d60fa507ac", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 1) Caenorhabditis elegans as a Genetic Organism](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "1097ef0b55cf321b80ebb20430f4aec4bb7a44c00673d3b41509d767b7c8daa4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Caenorhabditis elegans is a small, free-living soil nematode (roundworm) that lives in many parts of the world and survives by feeding on microbes, primarily bacteria (IntroFIG 1). It is an important model system for biological research in many fields including genomics, cell biology, neuroscience and aging (http://www.wormbook.org/). Among its many advantages for study are its short life cycle, compact genome, stereotypical development, ease of propagation and small size. The adult body plan is anatomically simple with about 1000 somatic cells. C. elegans is amenable to genetic crosses and produces a large number of progeny per adult. It reproduces with a life cycle of about 3 days under optimal conditions. The animal can be maintained in the laboratory where it is grown on agar plates or liquid cultures with E. coli as the food source. It can be examined at the cellular level in living preparations by differential interference contrast (DIC) microscopy, because it is transparent throughout its life cycle. The anatomical description of the whole animal has been completed at the electron microscopy level and its complete cell lineage, which is invariant between animals, has been established (Brenner, 1973; Byerly et al., 1976; Sulston et al., 1983; Wood, 1988a; Lewis and Fleming, 1995).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1307, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cc67dd86-44be-4c3b-9735-45f7a14c3ac4": {"__data__": {"id_": "cc67dd86-44be-4c3b-9735-45f7a14c3ac4", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 1) Caenorhabditis elegans as a Genetic Organism](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4286fd64-8096-45c2-badb-512edb1f15dc", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 1) Caenorhabditis elegans as a Genetic Organism](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "62058fba7c3e32d334a80522c5b32f6a001745f3497b612626adb38eb594b72c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "There are two C. elegans sexes: a self-fertilizing hermaphrodite (XX) and a male (XO). Males arise infrequently (0.1%) by spontaneous non-disjunction in the hermaphrodite germ line and at higher frequency (up to 50%) through mating. Self-fertilization of the hermaphrodite allows for homozygous worms to generate genetically identical progeny, and male mating facilitates the isolation and maintenance of mutant strains as well as moving mutations between strains.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 464, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "df4fcec3-d5bc-4aad-a5df-fa5b9036fb15": {"__data__": {"id_": "df4fcec3-d5bc-4aad-a5df-fa5b9036fb15", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 1) Caenorhabditis elegans as a Genetic Organism](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "93423870-cd63-43fe-9c4a-1b01ee17a2a1", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 1) Caenorhabditis elegans as a Genetic Organism](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "e2f4179f92225a3ce9f9ffbf5715a154eb361dbb71214e2af08a568b21d68682", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Mutant animals are readily obtained by chemical mutagenesis or exposure to ionizing radiation (Anderson, 1995; Jorgensen and Mango, 2002). The strains can be kept as frozen stocks for long periods of time. C. elegans can also endure harsh environmental conditions by switching to a facultative diapause stage called the dauer larva which can survive four to eight times the normal 3-week life span (Cassada and Russell, 1975).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 426, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5fdbc4dc-1d7c-4796-9661-18279a03b602": {"__data__": {"id_": "5fdbc4dc-1d7c-4796-9661-18279a03b602", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 1) Caenorhabditis elegans as a Genetic Organism](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b7266769-ba01-44f1-a4d8-187bcc6c2ce1", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 1) Caenorhabditis elegans as a Genetic Organism](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "a6751b988f22f3fc3bfef0168610193993ebbbc055b358bbb0e0996f43a28ac1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Despite its simple anatomy, the animal displays a large repertoire of behavior including locomotion; foraging; feeding; defecation; egg laying; dauer larva formation; sensory responses to touch, smell, taste, and temperature; and some complex behaviors like male mating, social behavior, and learning and memory (Rankin, 2002; de Bono, 2003).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 342, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d25f1a80-7b09-41ff-9925-b4f63c9eec1e": {"__data__": {"id_": "d25f1a80-7b09-41ff-9925-b4f63c9eec1e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 2.1) Body Shape](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f0c29188-832f-42f0-a0de-30bf802fd89a", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 2.1) Body Shape](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "3790723d6e4e295bd5baa845665ef02d30fe127913ab8e5bf788e5c0d22f98c3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Similar to other nematodes, C. elegans has an unsegmented, cylindrical body shape that is tapered at the ends (IntroFIG 1; IntroMOVIE 1). This is the typical nematode body plan, with an outer tube and an inner tube separated by the pseudocoelomic space (IntroFIG 2). The outer tube (body wall) consists of cuticle, hypodermis, excretory system, neurons, and muscles, and the inner tube comprises the pharynx, intestine, and, in the adult, gonad. All of these tissues are under an internal hydrostatic pressure, regulated by an osmoregulatory system (see Excretory System).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 572, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "aa3bbb90-7570-4ef2-ba3e-9f725c6029ac": {"__data__": {"id_": "aa3bbb90-7570-4ef2-ba3e-9f725c6029ac", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 2.2) Adult Hermaphrodite Organs and Tissues](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ba28d1f4-96ad-4996-bf6a-51002df8e708", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 2.2) Adult Hermaphrodite Organs and Tissues](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "c60b59a00f4c22864a4314e3a980a26c7e1e55c8e384b9c52d2dd9f1080a8dc3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Cuticle . A collagenous cuticle, secreted by the underlying epithelium, surrounds the worm on the outside and also lines the pharynx and rectum (see Cuticle). Various tissues open to the outside through this cuticle (IntroFIG 3). The excretory pore is located at midline on the ventral side of the head (IntroFIG 3E). The vulva is another large opening on the ventral side at the midbody (IntroFIG 3D), and the anus forms another ventral opening, just before the tail whip (IntroFIG 3B). Two cuticular inpockets form narrow openings at the lateral lips for the amphid sensilla (IntroFIG 4A and IntroTABLE 1). The lips also contain papillae for 6 inner labial (IL) sensilla and small bumps for 6 outer labial (OL) sensilla, as well as 4 cephalic (CEP) sensilla (IntroFIG 4A and IntroTABLE 1). There are two papillae for anterior deirids at the posterior of the head. These are situated within the lateral alae at the level of the excretory pore (IntroFIG4C and ExcFIG2B). The two posterior deirid sensilla are situated dorsal to the cuticular alae (IntroFIG 4B&C). Two much narrower openings on the lateral sides of the tail whip exist for the phasmid sensilla at the junction of the seam cells and the tail hypodermis (IntroFIG 4C).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1232, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "62adcb08-bbd6-4ccd-8fc5-3e139a8f2dd9": {"__data__": {"id_": "62adcb08-bbd6-4ccd-8fc5-3e139a8f2dd9", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 2.2) Adult Hermaphrodite Organs and Tissues](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ac637254-6949-4d7f-896d-c778e22f0db0", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 2.2) Adult Hermaphrodite Organs and Tissues](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "d05860bf8f7c2bbe7bbdbffb4dee1bad556cdcd8874dde2d5be34a412b1c9002", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The Epithelial System . The hypodermis, which secretes cuticle, is made up of the main body syncytium (hyp 7), a series of concentric rings of five smaller syncytial cells in the head, and three mononucleate and one syncytial cell in the tail (see Hypodermis). On the lateral sides, the hypodermis is interrupted by the syncytial row of seam cells which form alae on the cuticle surface during certain developmental stages (IntroFIG 3C) (see Seam Cells). The hypodermis and the inner tissues that open to the outside are connected to one another by specialized interfacial cells.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 579, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "44a855f1-6031-4716-b981-d27d64d80fc6": {"__data__": {"id_": "44a855f1-6031-4716-b981-d27d64d80fc6", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 2.2) Adult Hermaphrodite Organs and Tissues](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "39ba391e-10c7-4d3a-8fca-cdd7f6d89c7c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 2.2) Adult Hermaphrodite Organs and Tissues](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "1d3a7035ffe6cf5830f8d95fce9d43f8b12bbf868aa110d062c2fe96aec81956", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The Nervous System . The cells of the nervous system are organized into ganglia in the head and tail. The majority of C. elegans neurons are located in the head around the pharynx. In the body, a continuous row of neuron cell bodies lies at the midline, adjacent to the ventral hypodermis. In addition, there are two small posterior lateral ganglia on the sides, as well as some scattered neurons along the lateral body. The processes from most neurons travel in either the ventral or dorsal nerve cord and project to the nerve ring (NR) in the head which constitutes the major neuropil in the animal (IntroFIG 2C)(see Nervous System).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 635, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cffd60d4-f10a-4923-956e-a21516d4e9ed": {"__data__": {"id_": "cffd60d4-f10a-4923-956e-a21516d4e9ed", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 2.2) Adult Hermaphrodite Organs and Tissues](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "34f29a42-2a0e-45fd-8990-5de50b6c4134", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 2.2) Adult Hermaphrodite Organs and Tissues](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "4b693005ec69c375dbedc16de0a5209e25f18315530a7f6c58e8f7f946b83d00", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The Muscle System .  Neurons and the hypodermis are separated from the musculature by a thin basal lamina. The muscles receive input from the neurons by sending muscle arms to motor neuron processes that run along the nerve cords or reside in the nerve ring. The obliquely striated body wall muscles are arranged into strips in four quadrants, two dorsal and two ventral, along the whole length of the animal ( IntroFIG 2A-F ) (see Somatic Muscle System ). Smaller, nonstriated muscles are found in the pharynx and around the vulva, intestine and rectum (see Nonstriated Muscle System ).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 587, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c8de8815-9ae4-40e8-995c-9f31360005fb": {"__data__": {"id_": "c8de8815-9ae4-40e8-995c-9f31360005fb", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 2.2) Adult Hermaphrodite Organs and Tissues](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f256e88f-c7e6-4b65-8e30-c045c18cdeb1", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 2.2) Adult Hermaphrodite Organs and Tissues](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "358de3391926a265cc0ff9afe5cdee9978810966fc5986fc63f5f9e83c004023", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The Excretory System . Four cells situated on the ventral side of the posterior head make up the excretory system, which functions in osmoregulation and waste disposal. The excretory system opens to the outside through the excretory pore ( IntroFIG 3E ) (see Excretory System ).2.2.2 Pseudocoelomic Cavity Organs", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 312, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c930787f-0e67-4f84-bcf0-b90688b479bf": {"__data__": {"id_": "c930787f-0e67-4f84-bcf0-b90688b479bf", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 2.2) Adult Hermaphrodite Organs and Tissues](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "49ce2c1c-e750-4c2c-8d56-6522cc89827f", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 2.2) Adult Hermaphrodite Organs and Tissues](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "270134b44edbfc010e392d282c871d06c07535474f2fc72e06f01318cd1b42d6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The Coelomocyte system. Three pairs of coelomocytes located in the pseudocoelomic cavity function as scavenger cells that endocytose fluid from the pseudocoelom and are suggested to comprise a primitive immune system in C. elegans (see Coelomocyte System).\n\n2.2.3 Internal Organs", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 279, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c6b405ba-bd2b-4bf2-87f2-d3ace4cbf5e1": {"__data__": {"id_": "c6b405ba-bd2b-4bf2-87f2-d3ace4cbf5e1", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 2.2) Adult Hermaphrodite Organs and Tissues](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bd9ed0f8-fd5b-4f6d-956b-64461334ebd0", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 2.2) Adult Hermaphrodite Organs and Tissues](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "e9c1e046c3bd570481b5dc023dc68c99f4c2ce48eadcae4c503d70aff4595f63", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The Alimentary system .C. elegans feeds through a two lobed pharynx, which is nearly an autonomous organ with its own neuronal system, muscles, and epithelium (IntroFIG 1). The pharynx is separated from the outer tube of tissues and pseudocoelom by its own basal lamina (IntroFIG 2B-D). The lumen of the pharynx is continuous with the lumen of the intestine, and the pharynx passes ground food into the intestine via the intestinal pharyngeal valve. The intestine, which is the only somatic tissue derived from a single (E blast cell) lineage, is made of 20 cells arranged to form a tube with a central lumen. The apical surfaces of the intestinal cells carry numerous microvilli. The intestinal contents are excreted to the outside via a rectal valve that connects the gut to the rectum and anus. The four enteric muscles that contribute to defecation are located around the rectum and posterior intestine (see Alimentary System Sections: Pharynx, Intestine and Rectum and Anus).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 980, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e7490988-6a57-4489-bff7-d91437e3b148": {"__data__": {"id_": "e7490988-6a57-4489-bff7-d91437e3b148", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 2.2) Adult Hermaphrodite Organs and Tissues](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5bda78db-4e28-415e-9841-01aeaa17f4e4", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 2.2) Adult Hermaphrodite Organs and Tissues](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "5f5dc0db7821fa30d38c3a5da555830c070c376a60bf727c498ed26cf92e9b59", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The Reproductive system . This system consists of somatic gonad, the germ line and the egg-laying apparatus. There are two bilaterally symmetric, U-shaped gonad arms that are connected to a central uterus through the spermatheca (IntroFIG 1). The germ line within the distal gonad arms (ovaries) is syncytial with germline nuclei surrounding a central cytoplasmic core. More proximally, germ cells pass sequentially through the mitotic, meiotic prophase and diakinesis stages. As they pass through the bend of the gonad arm (oviduct), oocytes enlarge, detach from the syncytium, and mature as they move more proximally. The oocytes are fertilized by the sperm in spermatheca. The resulting diploid zygotes are stored in the uterus and laid outside thorough the vulva, which protrudes at the ventral midline (see Reproductive System: Somatic Gonad, Germ Line and Egg-laying Apparatus).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 884, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "dea66e63-8198-4ba5-8a22-4686743501e0": {"__data__": {"id_": "dea66e63-8198-4ba5-8a22-4686743501e0", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 2.3) Adult Male Anatomy](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "009de985-77a7-4bbc-9d28-6b030a410a77", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 2.3) Adult Male Anatomy](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "ec05a09463404ce87870322fb30c7f8e7213aae99bd733cd31b0b82380a7b87d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The male anatomy is the subject of a separate section (Male Handbook), but here we provide an overview of major differences between the male and the hermaphrodite sexes. Male C. elegans larvae initially display the same simple cylindrical body plan as hermaphrodites, but from the L2 stage onward, the shape of their posterior half changes as their sexual organs begin to develop (IntroFIG 5) (Sulston and Horvitz, 1977; Sulston et al., 1980; Nguyen et al., 1999). With the exception of perhaps the pharynx and the excretory system, virtually all tissue systems exhibit some degree of sexual dimorphism. The most profound differences are seen in tissues of the posterior, which bears the male copulatory apparatus. The muscle system of the male contains 41 additional sex-specific muscles (see Male-Specific Muscles). The reproductive system consists of a single-armed gonad (IntroFIG 5C; Male Somatic Gonad and Germline) that opens to the exterior at the cloaca (anus) via a modified rectal epithelial chamber called the proctodeum (IntroFIG 5D) (see Proctodeum). The proctodeum includes two sclerotic sensory spicules used by the male during mating to locate the hermaphrodite vulval slit and to hold the vulva open during sperm transfer (Liu and Sternberg, 1995; Garcia et al., 2001). The nervous system has 91 additional neurons that include several classes of tail sensilla: the rays, which extend from the tail and lie in a cuticular fan (see Rays); the hook (see Hook); and the post-cloacal sensilla, which are located on the ventral exterior of the tail (see PCS).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1572, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c71d1b36-a82f-40c3-a568-69a8b698a3eb": {"__data__": {"id_": "c71d1b36-a82f-40c3-a568-69a8b698a3eb", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3) Life cycle](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d763a006-a294-4f0a-8dae-c6f261f5de3c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3) Life cycle](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "907c8daa11be7b234d6d6214adb3eceb2a455ac51554b9fe47adf6618eb6988d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Similar to other nematodes, the life cycle of C. elegans is comprised of the embryonic stage, four larval stages (L1-L4) and adulthood. The end of each larval stage is marked with a molt, during which a new, stage-specific cuticle is synthesized and the old one is shed. During this period, pharyngeal pumping ceases and the animal enters a brief lethargus (IntroFIG 6; IntroMOVIE 2).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 384, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "33cc0f3b-2202-4370-8fb5-e4759d533672": {"__data__": {"id_": "33cc0f3b-2202-4370-8fb5-e4759d533672", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3) Life cycle](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0187d616-f2ce-4c90-a5c1-ea26896a26c3", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3) Life cycle](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "833740087879971d0f102d9e3181131e84bba7e9664acf5de9b3749c178ea61e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "3.1 Embryo", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 10, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4b831a72-d90b-4f0f-be71-064886d3b911": {"__data__": {"id_": "4b831a72-d90b-4f0f-be71-064886d3b911", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3bcbca4b-6175-4c68-bed3-f35d51691e0e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "116b3d9cabd1214347239f28ffe6112204ba323d3bb70548769ee04b95908f85", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Embryogenesis in C. elegans is roughly divided into two stages: (1) proliferation and (2) organogenesis/ morphogenesis (IntroFIG 7) (Sulston et al, 1983). Proliferation (0 to 330-350 min post-fertilization at 22'C) includes cell divisions from a single cell to about 550 essentially undifferentiated cells by the end of the '16 E stage' (von Ehrenstein and Schierenberg, 1980; Wood, 1988b). This stage is further subdivided into two phases: The first phase (0-150 min) spans the time between zygote formation to generation of embryonic founder cells, and the second phase (150-350 min) covers the bulk of cell divisions and gastrulation until the beginning of organogenesis (Bucher and Seydoux, 1994). The initial 150 min of proliferation takes place within the mother's uterus, and the embryo is laid outside when it reaches the approximate 30-cell stage (at gastrulation). There is considerable rearrangement of cells in the proliferation stage because of short-range shuffling, and once gastrulation begins, because of specific cell migrations (during gastrulation Ea and Ep sink in from the posterior and enter into the embryo at 100 min after first cell cleavage. P4 and MS progeny enter at 120-200 min, followed by C and D myoblasts entering from the posterior. AB-derived pharynx progenitors enter inside at 210-250 min. Once the cell migrations are completed, ventral cleft through which cells migrated in closes proceeding from the posterior (230 min) to anterior. Ventral cleft closure is completed at 290 min.) From this time onward, the embryonic substages can be defined by specific cell migrations, gain in cell number, and periods of synchronous stem-cell divisions.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1681, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "236e037e-16da-4b47-b5b8-c52afbc1eb48": {"__data__": {"id_": "236e037e-16da-4b47-b5b8-c52afbc1eb48", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "59fcfae9-db9f-4f2a-b0b4-1bebc617867f", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "5759bc6c8fce98f66a4f47f8b561400a32d530637381dcb5d8f477fc462ccb31", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "At the end of the proliferation stage, the embryo is a spheroid of cells organized into three germ layers: ectoderm, which gives rise to hypodermis and neurons; mesoderm, which generates pharynx and muscle; and endoderm, which gives rise to germline and intestine. During the organogenesis/morphogenesis stage (5.5-6 hr to 12-14 hr), terminal differentiation of cells occurs without many additional cell divisions, and the embryo elongates threefold and takes form as an animal with fully differentiated tissues and organs. Morphogenesis starts with the 'lima bean' stage. The first muscle twitches are observed at 430 min after the first cell cleavage (between 1.5- and 2-fold stages) (IntroFIG 7). Sexual dimorphism becomes visible for the first time at 510 minutes when the cephalic companion neurons (CEMs) die in the hermaphrodite, and when the hermaphrodite-specific neurons (HSNs) die in the male. In the late three-fold stage, the worm can move inside the egg in a coordinated fashion (rolling around its longitudinal axis), indicating advanced motor system development. The embryo starts pharyngeal pumping at 760 min after the first cell cleavage and hatches at 800 min (von Ehrenstein and Schierenberg, 1980; Sulston et al, 1983; Bird and Bird, 1991).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1262, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9ebdb5c1-3e27-4898-b36b-ff1dad682972": {"__data__": {"id_": "9ebdb5c1-3e27-4898-b36b-ff1dad682972", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a5d67bbd-53c2-4c3d-b295-52014cecaaac", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "e93ff085029a246fdb665a333c665713287be8f94c7c35e644b5cfee326b1df3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The main body plan of the animal is already established at the end of embryogenesis. This general body plan does not change during postembryonic development.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 157, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6ea93431-3180-4481-9155-b6449e005843": {"__data__": {"id_": "6ea93431-3180-4481-9155-b6449e005843", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "84b97a4c-33af-44f1-afda-058150287341", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "7d91e3080752e39632b55c66213f38cc04821a0a1715ef17e1d9043f96b3b23c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "3.2 Post-embryonic Development", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 30, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "78a44e27-5409-4916-b3e7-012b0b6e3d5f": {"__data__": {"id_": "78a44e27-5409-4916-b3e7-012b0b6e3d5f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d00543e0-f1e8-4a7e-b736-b1a387579f87", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "f47c55248324d47e77b21bf4a3493194a01741837f23b7ee8435e7ff8411ea1d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Post-embryonic development is triggered by feeding after hatching. In the presence of food, cell divisions resume and the post-embryonic developmental program begins 3 hours after hatching (Ambros, 2000). The animal normally passes through four larval stages to reach adulthood (IntroFIG 8, IntroMOVIE 2). Numerous blast cells set aside at the end of embryogenesis divide in nearly invariant temporal and spatial patterns through the four larval stages and give rise to a fixed number of cells with determined fates (see Cell lineages; Sulston and Horvitz, 1977; Wood 1988b). Of the 671 nuclei generated in the embryo, 113 undergo programmed death in the course of development (Sulston et al, 1983; Bird, and Bird, 1991). About 10% of the remaining 558 cells in a newly hatched larva (51 in hermaphrodites, 55 in the male) are blast cells that will divide further (Sulston and Horvitz, 1977; von Ehrenstein and Schierenberg, 1980). If the embryos hatch in the absence of food, however, they arrest development until food becomes available. Such larvae can survive up to 6-10 days without feeding (IntroFIG 6) (Johnson et al., 1984). After food becomes available, these arrested L1 stage larvae progress through normal molting and development (Slack and Ruvkun, 1997).\n\n3.2.1 L1 Larva", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1283, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d346e85e-9e34-4dfe-94ea-0d9cac03cabb": {"__data__": {"id_": "d346e85e-9e34-4dfe-94ea-0d9cac03cabb", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a1c954ab-f955-4481-81d2-dcd3428d82bf", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "bc917a410c04407719f4f1e746df4c07ca7080e73348f62d817ae228b247fb8c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Nervous system . Of the eight classes of motor neurons (DAn, DBn, VAn, VBn, VCn, ASn, VDn, and DDn) in the adult hermaphrodite ventral cord, five (VAn, VBn, VCn, ASn and VDn) are generated at the end of the L1 stage from 13 precursors (W and P1-P12) (IntroFIG 8A) (Sulston, 1976; Sulston and Horvitz, 1977; Chalfie and White 1988). A few other neurons are generated from Q, G1, H2 and T blast cells. Also, during the L1 stage, one class of ventral cord motor neurons (DDn) go through complete synaptic reorganization without any cell-shape change. The initial pattern of synapses made by DD neurons is presynaptic and inhibitory to ventral body wall muscles, while being postsynaptic to neurons that activate dorsal body wall muscles. During late L1, after the birth of VD motor neurons, DD neurons change their synaptic pattern such that their dorsal branches become presynaptic and inhibitory to dorsal body wall muscles, whereas their ventral branches become postsynaptic to excitatory neurons that synapse on ventral body wall muscles (White et al., 1978; Walthall et al., 1993).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1083, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e23116b2-3943-45cd-b588-fcbd0cd13f89": {"__data__": {"id_": "e23116b2-3943-45cd-b588-fcbd0cd13f89", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "122ba4ef-567f-461d-b114-f9dee0cd4198", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "790c875df4ab7bb195b875e63d09e1821999cab43d72d449b0a7b859ac0aebd1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Reproductive System. During the second half of L1, somatic gonad precursors Z1 and Z4 produce 12 cells in the hermaphrodite (IntroFIG 8C). The germ line precursors Z2 and Z3 also start to divide. These Z2-Z3 divisions occur continuously from L1 through adulthood (Kimble and Hirsh, 1979). Ventral Pn.p cells are born. A central subset will give rise to the vulva in L3 and L4.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 376, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cb8ac8f3-7b1f-4f9e-b74f-77f6a3f37e9c": {"__data__": {"id_": "cb8ac8f3-7b1f-4f9e-b74f-77f6a3f37e9c", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bc8c7374-99da-44ba-90c6-ec30456d304f", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "6b1781e4d7687623e74ed8a8798296ff5e7303742cc04db96e86791d8b9e7abb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Coelomocyte system. By the end of the L1 stage, the M mesoblast gives rise to two additional (dorsal) coelomocytes in the hermaphrodite (IntroFIG 8A).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 150, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6c12d627-b52b-4707-973e-68dfcba834ef": {"__data__": {"id_": "6c12d627-b52b-4707-973e-68dfcba834ef", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6cbc251b-289e-484a-a4ca-494ddb9749f5", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "984d8080097aae411ce997ef138fb5fcab6fec149018b0322f9093ec35c01c8c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Male. At hatching, males are already distinguishable from hermaphrodites because of the more posterior location of one ventral coelomocyte, the larger size of the nuclei of two rectal cells (B and Y), the absence of hermaphrodite specific neurons (HSNs) that undergo programmed cell death during embryogenesis, and the presence of CEM neurons. As in the hermaphrodite, Z1 and Z4 divide, producing 10 somatic gonad precursor cells. Rectal blast cells B and Y, which will ultimately generate the proctodeum and posterior sensory structures, begin to divide towards the end of L1.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 577, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8f5c2f85-2e18-4891-9486-fa1d2157836f": {"__data__": {"id_": "8f5c2f85-2e18-4891-9486-fa1d2157836f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4b6e9d25-160d-46d8-b2a7-8e4087c1889f", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "2164a23158357a0055826346590db8cd1884ee4923a416f48b3d45f0256e7333", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Few cell divisions occur during the L2 stage.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 45, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "20cd187d-b423-4e17-b907-b8609941ccd6": {"__data__": {"id_": "20cd187d-b423-4e17-b907-b8609941ccd6", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cffa75de-d5da-4209-95b6-1e4420e8f358", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "fcb29dd7e47e0ad2650a38ca2a18ef55c06ebb9a8273ec0805722b3435eeab24", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Nervous system. V5.pa generates the postdeirid sensilla and G2 produces two ventral ganglion neurons.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 101, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f3004c11-94a0-486c-aefd-2602388fca3d": {"__data__": {"id_": "f3004c11-94a0-486c-aefd-2602388fca3d", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c987849e-7a4b-4191-8639-86d9318b72e8", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "0b0549a4f1e4c8ee73e0cb78506684595928fe1954acff6fa4b510a7850b7e4f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Reproductive system. In this stage, the germ cell (Z2 and Z3 daughters) divisions continue, approximately quadrupling in number (IntroFIG 8D). However, no divisions occur in Z1 and Z4 (somatic primordial gonad) lineages. Somatic and germ cells are intermingled until the L2/L3 molt whereupon they rearrange to establish the general organization of the future gonad: distal tip cells positioned at the anterior and posterior ends, an anterior and posterior arm germ-line population, and a somatic gonadal primordium at the center (Kimble and Hirsh, 1979). The gonad begins to elongate, led by the DTC cells.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 606, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "11a523be-c05b-4ef6-8459-430e4bf533b5": {"__data__": {"id_": "11a523be-c05b-4ef6-8459-430e4bf533b5", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "62549c02-d473-4cc8-b3bf-b9c0851e4f53", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "fadad200b115b03c8f014105090312cec23a580a42b26142b42a0033870ca59b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Male. Cells of the male gonad also rearrange to resemble the adult form, with somatic gonad cells towards the posterior and germ cells displaced to the anterior. At about the L1/L2 molt, the gonad extends, but only at one end, and is led by the linker cell (Antebi et al., 1997). Approximately at the mid-L2 stage, the linker cell halts and reorients to move dorsally.\n\n3.2.3 Dauer Larva - see Dauer Handbook", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 408, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3ad0efc3-2e55-483a-9e71-2c374e796807": {"__data__": {"id_": "3ad0efc3-2e55-483a-9e71-2c374e796807", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "62a2c488-cf25-4e4e-81a3-2280d0fd15d3", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "512465f9f5881dbac7506c93c910f3710569693df8fc1c16e0614d52baf4cb58", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "At the end of the L2 stage, the animal may enter an arrested state called the dauer larva if the environmental conditions are not favorable for further growth. Environmental factors, including the presence of a pheromone (an indicator of population density), absence of food, and high temperature act as signals that can trigger formation of a morphologically distinct L2-stage larva, designated L2d (see Regulation of Diapause). The critical period for this dauer signal begins after the middle of the first larval stage.\u00a0The L2d larva retains the potential to form either a dauer larva or an L3 larva, depending on the persistence of the dauer inducing environmental parameters (Riddle, 1988). If the environment continues to be disadvantageous, the L2d-stage larva molts into a dauer (IntroFIG 6). The dauer is a non-aging state because its duration does not affect postdauer life span. During the dauer state, feeding is arrested indefinitely and locomotion is markedly reduced. The dauer state ends when the animal experiences favorable conditions. Within 1 hour of accessing food, the animal exits the dauer stage; after 2-3 hours it starts to feed, and after about 10 hours, it molts to the L4 stage.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1207, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8da12596-523b-43f1-9d5a-fa492a112999": {"__data__": {"id_": "8da12596-523b-43f1-9d5a-fa492a112999", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b17d3354-c93a-4fc4-84f6-6af493c5f18d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "463d2dc460c4437215a93608bfe5e6ab0e161d842ab4e63d74ae8eb0888f6c11", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Morphologically, dauer larvae are very thin (with a length-width ratio of about 30:1) and have a thick, altered cuticle (DCutFIG 1 and DCutFIG 2) (see Cuticle System and Dauer Cuticle). The buccal cavity is sealed by a cuticular block (DCutFIG 4), the gut cells have a dark appearance and the pharyngeal and intestinal lumens are shrunken (DPhaFIG 4), with small and indistinct microvilli in the intestine (see Dauer Pharynx and Dauer Intestine). The excretory gland lacks secretory granules, although the excretory pore remains open (see Dauer Excretory). The gonad of the dauer is arrested at the L2 stage (IntroFIG 8E) (Cassada and Russell, 1975; Riddle, 1988; Sulston, 1988).\n\n3.2.4 L3 Larva", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 695, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5edd73df-02e8-47e1-bde0-7271ef9f66b0": {"__data__": {"id_": "5edd73df-02e8-47e1-bde0-7271ef9f66b0", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a6bdf02c-e489-4a6e-b48c-a613fc5a949c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "635c9b564a447fc6ae8d9d05226fb7542604313c3706363c4409a3dd1fe87e9a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Reproductive system . During L3, as well as the first part of L4, somatic gonad precursors yield a total of 143 cells that form the anterior and posterior gonadal sheaths, the spermathecae and the uterus (Kimble and Hirsh, 1979). The extension of gonad arms continues in opposite directions until mid-L3 when distal tip cells halt and then slowly start to reorient themselves in dorsal directions (Antebi et al., 1997) (IntroFIG 8F, also see Somatic Gonad). Vulval precursor fates are specified, and committed cells divide to generate vulval terminal cells by early L4. The two sex myoblasts, formed in L3, divide to generate16 sex muscle cells (see Egg-Laying Apparatus).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 672, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "300323ac-4e7a-4121-bc53-d73eaa8ea7ab": {"__data__": {"id_": "300323ac-4e7a-4121-bc53-d73eaa8ea7ab", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2dbbae0f-a928-4ece-9c47-967bf7045d4b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "a928045e4abd89ee9264998f136bf619913011b244789fdf14c8d0a77b4e41ad", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Male. Somatic gonad blast cells divide to generate 53 somatic gonad cells that will form the vas deferens and the seminal vesicle. The male linker cell of the somatic gonad reorients and migrates posteriorly until mid-L3 extending the proximal gonad. After mid-L3, the male linker cell migrates obliquely towards the ventral midline (Antebi et al., 1997). Six male sex myoblasts are generated. As posterior blast cells divide, the tail become visibly swollen when viewed under the dissecting scope (IntroFIG 5E). Posterior Pn.p cells divide to add 16 cells to the preanal ganglion. More anterior Pn.p lineages contribute cells to the ventral nerve cord. Rectal lineages produce proctodeal cells and several tail sensilla (Sulston et al., 1980; Sulston, 1988). In the male germline, which produces only sperm, meiosis begins during L3 stage.\n\n3.2.5 L4 Larva", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 856, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e44643a5-fc2a-4171-98ac-447cc0e5c1d2": {"__data__": {"id_": "e44643a5-fc2a-4171-98ac-447cc0e5c1d2", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "331b06aa-2854-4598-b532-055314538d76", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "60363df132e5fd2ecd3ecf6e51a83990a28c4e1b56bad948e9467ae00df1a5a8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Reproductive system. Gonadogenesis, which starts at approximately 7 hours after hatching, is completed in the L4 stage. The distal gonad arms continue their migration centripetally along the dorsal body wall muscles, and by the L4/adult molt, they complete their trajectory close to midline (Antebi et al, 1997). Meiosis in the germ line begins at L3/L4 molt in the proximal arms of the gonad, and the germ cells differentiate into mature sperm. At the L4/adult molt, sperm production stops and the remaining germline cells  continue to undergo meiosis and differentiation to generate exclusively oocytes instead. Vulval and uterine terminal cell generation is followed by tissue morphogenesis (IntroFIG 8G). Egg-laying neurons (VCs and HSNs) and sex muscles, generated from sex myoblasts, associate with these structures to form the egg-laying apparatus. (Greenwald, 1997).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 874, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b52b21e7-7cde-4f70-b42e-104d352c01fb": {"__data__": {"id_": "b52b21e7-7cde-4f70-b42e-104d352c01fb", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e3d6a29d-bb79-4ccd-9a26-3b1d18a1ba22", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "3718bfa789db70315bf981b42a57b86788739dfda5e30847251a22a71516c8d1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Male. 41 male sex muscles and a coelomocyte are formed from the M mesoblast lineage during the L4 stage in males (Sulston et al., 1980). The cells around the rectum form the proctodeum. This epithelium expands to surround the cloacal chamber, which contains the spicules. The gonad continues to grow posteriorly along the ventral midline, and the vas deferens and the seminal vesicle differentiate. The linker cell reaches the developing cloaca by mid-L4 where it dies and is then engulfed by two cells of the proctodeum, thereby opening the vas deferens to the outside (Sulston, 1988; Antebi et al., 1997). Tail tip hypodermal cells remodel, generating the rounded tail of the adult (IntroFIG 5E) (Nguyen et al., 1999). The tail seam (SET) is formed. Eventually, a general forward movement of posterior tissues and collapse of the cuticle reshape the male tail and generates the copulatory bursa with rays and fan, as well as the ventral hook and post-cloacal sensilla (Emmons and Sternberg, 1997).\n\n3.2.6 Adult", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1012, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "78da4585-1c7f-46e5-a3af-e10dbd0163c3": {"__data__": {"id_": "78da4585-1c7f-46e5-a3af-e10dbd0163c3", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "402cf5ea-fbd7-4591-ab68-f6ddaeb339e9", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "9c7baf3409be34d0f48429101df7ec3bd81d6a3f4c3dcaff9788f0a871971af5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "At approximately at 45-50 hrs posthatch at 22'C-25'C, a newly matured hermaphrodite lays its first eggs, hence completing its 3-day reproductive life cycle (Byerly et al., 1976; Lewis and Fleming, 1995). The adult hermaphrodite produces oocytes for about 4 days, and after this fertile period of 3-4 days, the mature adult lives for an additional 10-15 days. A hermaphrodite that self-fertilizes can produce about 300 progeny because of the limited number of sperm, but if mating with a male occurs, the progeny number can increase to 1200-1400. Males can successfully mate with a hermaphrodite for 6 days after their last larval molt and can father approximately 3000 progeny (Hodgkin, 1988).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 693, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8ef435d8-31d2-4e01-aca9-145b826f65b9": {"__data__": {"id_": "8ef435d8-31d2-4e01-aca9-145b826f65b9", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c5d6060f-b8fa-45b8-88d4-54899d9847a5", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Introduction, Section 3.1) Embryo](https://www.wormatlas.org/hermaphrodite/introduction/Introframeset.html)"}, "hash": "bb901d9acf95b59f3f18933a0e1cd8ec72c9518d79a2a63547a141337aed820a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Out of 1090 somatic cells generated during hermaphrodite development, 131 undergo programmed cell death at characteristic times (Driscoll, 1995). Hence, the adult C. elegans hermaphrodite has 959 somatic nuclei, 302 of which are neurons and 95 are body wall muscle cells (White, 1988). The adult male, on the other hand, has 1031 somatic nuclei and 381 of these are neurons (extra neurons are mostly dedicated to male mating behavior) (White, 1988). Although it has more cells, the adult C. elegans male is more slender and slightly shorter (approx. 0.8 mm) than the hermaphrodite (IntroFIG5). For detailed review of anatomic structures in male, refer to Male Handbook.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 669, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "61dafc5b-60e5-42f4-8326-921067c95efb": {"__data__": {"id_": "61dafc5b-60e5-42f4-8326-921067c95efb", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Atypical epithelial cells, Section 1) XXX Cells](https://www.wormatlas.org/hermaphrodite/atypical/Atypframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "918b1292-1409-4dcc-afb5-a69e19a90310", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Atypical epithelial cells, Section 1) XXX Cells](https://www.wormatlas.org/hermaphrodite/atypical/Atypframeset.html)"}, "hash": "2bd70c54821a070792b7cd82a9cb39bb566f3267befa461dbe21df03cc221bcc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The two XXX cells, XXXL/R, derive from the AB lineage as sisters of the anterior hypodermal (hyp 5) cells. They are born around 260 minutes after first cell cleavage on the dorsal side of the embryo and adjacent to the nascent hyp 5 and hyp 6 cells (Sulston et al., 1983). Similar to anterior hypodermal cells, they later translocate to the ventral anterior side of the embryo and are positioned close to the ventral hyp 4 cells in tadpole stage (AtypFIG 1).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 458, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8f17f832-5cef-478a-9c4d-37dab526f27b": {"__data__": {"id_": "8f17f832-5cef-478a-9c4d-37dab526f27b", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Atypical epithelial cells, Section 1) XXX Cells](https://www.wormatlas.org/hermaphrodite/atypical/Atypframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f925cb24-e430-437d-be74-4e03ff5e00eb", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Atypical epithelial cells, Section 1) XXX Cells](https://www.wormatlas.org/hermaphrodite/atypical/Atypframeset.html)"}, "hash": "836e807fddfb5c361253f854fe0e7d8da5c56565d56e150ca02462bf82116114", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "XXX cells function as part of the anterior hypodermis in the embryo, but they eventually detach from it and translocate near the anterior bulb of the pharynx on the ventral side of the head and lose their hypodermal character (AtypFIG 2) (White, 1988). They become free-standing cells adjacent to the pseudocoelom. Although they are generally found anterior to the nerve ring, their positions can be variable, and occasionally they reside anterior to the metacorpus of the pharynx (Sulston et al., 1983). After losing their hypodermal features, structurally they become neuron-like with compact cell bodies; small, granulated nuclei; and with several, short, axon-like processes. The thin, flattened, posterior process faces the pseudocoelom outside the pharynx rather similar to the processes of GLR cells (AtypFIG 3). The tubular anterior process travels a short distance with the ventral labial process bundles. In some animals, this process can extend as far anteriorly as the tip of the head (Ohkura et al., 2003). In dauer larvae, XXX cells may grow a long posterior process that does  not enter the nerve ring. These cells have no intercellular junctions and make no obvious synapses, but they remain in close contact with labial neurons, hypodermis and the pseudocoelom. They have abundant ribosomes, some smooth ER and a few vesicles.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1343, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "866accaf-609f-4a26-b6be-7d19bf1edcc5": {"__data__": {"id_": "866accaf-609f-4a26-b6be-7d19bf1edcc5", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Atypical epithelial cells, Section 1) XXX Cells](https://www.wormatlas.org/hermaphrodite/atypical/Atypframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5e265d11-6b46-448d-ad63-b35a5fb53a5b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Atypical epithelial cells, Section 1) XXX Cells](https://www.wormatlas.org/hermaphrodite/atypical/Atypframeset.html)"}, "hash": "20bbc653e55e2e790f2bbf03135095f312bc00510096ff6763ca55c19af15f84", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "XXX cells likely perform a neuroendocrine secretory function in larvae; they have been implicated in regulation of dauer arrest, but not longevity, by the insulin signaling pathway (Kimura et al., 2011.) XXX cells express NCR-1 and NCR-2, homologs of a membrane glycoprotein (Niemann-Pick type C disease gene product) suggested to function in intracellular sterol trafficking (Sym et al., 2000; Li et al., 2004). They also express DAF-9, a cytochrome P450 of the CYP2 family, that is suggested to mediate synthesis of steroid hormones, and DAF-2, insulin/IGF-1 receptor that functions upstream of DAF-9 (Jia et al., 2002; Ohkura et al., 2003; Tatar et al., 2003; Gerisch and Antebi, 2004; Kimura et al., 2011). DAF-9 functions in the same pathway as DAF-12, a nuclear hormone receptor that is thought to bind sterol derivatives and mediate the choice of dauer stage versus reproductive growth (Antebi et al., 2000; Gerisch et al., 2001; Mak and Ruvkun, 2004). SDF-9, a protein tyrosine phosphatase, is thought to help the function of DAF-9 and is also expressed in XXX cells (Ohkura et al., 2003).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1097, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0a5b6ad6-d233-49f1-9ca8-0c3916069b9a": {"__data__": {"id_": "0a5b6ad6-d233-49f1-9ca8-0c3916069b9a", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Atypical epithelial cells, Section 2) Tail Spike Scaffold Cells](https://www.wormatlas.org/hermaphrodite/atypical/Atypframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d42150b8-49d5-4adb-a2f5-ee2e483cda5f", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Atypical epithelial cells, Section 2) Tail Spike Scaffold Cells](https://www.wormatlas.org/hermaphrodite/atypical/Atypframeset.html)"}, "hash": "7bae5d7fdad4384db71b7d31f46421b9eac9c165821a04b4a5167e15d048e599", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Two short-lived hypodermal cells, ABplppppppa and ABprppppppa, in the tail tip of the early embryo fuse to form a syncytium by the tadpole stage embryo, but undergo programmed cell death during late embryogenesis and leave behind a narrow spike of cuticle (Sulston et al., 1983). Their nuclei lie in the anal ridge, near hyp 10 and hyp 9 (AtypFIG 1 and AtypFIG 4). The syncytial cell is small, has somewhat darker cytoplasm than nearby hypodermis, and extends a single posterior process to the extreme tail tip. This process is filled with microtubules, called filaments by Sulston et al. (1983). These filaments give this process the appearance of a primitive cilium AtypFIG 4C). The process is wrapped by hyp10 over most of its length, whereas only the very tip of the process is exposed to the cuticle. Specialized junctions (probably gap junctions, but also possibly some adherens junctions) are seen between the tail spike cell and hyp 10 when the embryo reaches the twofold stage. The posterior cilium may provide a scaffold over which hyp 10 forms a broader, more stable posterior extension to give shape to the tail tip. When the spike cells die, hyp 10 still has a posterior process in place to maintain and support the cuticular spike directly.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1254, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d208fbbc-6a5c-4f8e-b7dd-9b8016bc1273": {"__data__": {"id_": "d208fbbc-6a5c-4f8e-b7dd-9b8016bc1273", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Atypical epithelial cells, Section 3) List of Atypical Epithelial Cells](https://www.wormatlas.org/hermaphrodite/atypical/Atypframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "69aaa8cf-30bc-4f5f-82a2-2a92df136883", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Atypical epithelial cells, Section 3) List of Atypical Epithelial Cells](https://www.wormatlas.org/hermaphrodite/atypical/Atypframeset.html)"}, "hash": "ecea6557ff717b4a0050f325d95c4abdff36f653340857d5980f4683de642e50", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "1. XXX cells \n\nXXXL\n\nXXXR\n\n2. Tail spike scaffold cells\n\nABplppppppa\n\nABprppppppa", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 81, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6c89ed2a-5c00-4ce3-8ced-0bf3692f108c": {"__data__": {"id_": "6c89ed2a-5c00-4ce3-8ced-0bf3692f108c", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Atypical epithelial cells, Section 4) References](https://www.wormatlas.org/hermaphrodite/atypical/Atypframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b102f452-6be8-4fb1-b554-62272a27fa71", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Atypical epithelial cells, Section 4) References](https://www.wormatlas.org/hermaphrodite/atypical/Atypframeset.html)"}, "hash": "78e47f84e6ec58c72f6ecdae25166122d215c8f195d2d38610fa745aa82d4003", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "White J. 1988. The Anatomy. In The nematode C. elegans (ed. W. B. Wood). Chapter 4. pp 81-122. Cold Spring Harbor Laboratory Press, New York. Abstract", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 150, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "415d5a33-f8ec-4628-903d-c7631dd277ff": {"__data__": {"id_": "415d5a33-f8ec-4628-903d-c7631dd277ff", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Hypodermis, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/hypodermis/Hypframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "53901692-0c3a-4b2b-98ee-c9ebaadea13a", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Hypodermis, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/hypodermis/Hypframeset.html)"}, "hash": "41b9acad125603429c179fd3975fef4ea846e58c80f1f3f7c72a33768cc4aead", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The epithelial system of C. elegans constitutes two general categories of cells: hypodermis and specialized epithelial cells. The hypodermis is made of the main body syncytium (hyp 7) and smaller hypodermal cells of the head and tail. The specialized epithelial cells secrete parts of the cuticle, direct the formation of specialized structures in the cuticle, and act as support cells (glia) for neuronal sensory receptors and as linker cells to attach the hypodermis to internal tissues while forming various holes in the cuticle.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 532, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c9a75d0d-0ad5-442e-971d-b0c737ecfc95": {"__data__": {"id_": "c9a75d0d-0ad5-442e-971d-b0c737ecfc95", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Hypodermis, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/hypodermis/Hypframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e5bf83e7-77d6-4ec0-8dbd-ed19e953d9bd", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Hypodermis, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/hypodermis/Hypframeset.html)"}, "hash": "7c7c522b6c0ea0db24395571b0df8cef7774e188b69999fd7365a279709d89c6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The hypodermis performs many functions during early development, including establishing the basic body plan, depositing basement membrane components, regulating cell fate specification of neighboring cells, guiding cell and axon migrations, and taking up apoptotic cell bodies by phagocytosis (Johnstone and Barry, 1996; Greenwald, 1997; Michaux et al., 2001). As the animal matures, the hypodermis is also important for storage of nutrients and deposition of stage-specific cuticles (molting), and it provides a barrier function for the pseudocoelomic cavity (Singh and Sulston, 1978; White, 1988; Kramer, 1997; Yochem et al., 1999; see also The Cuticle and Dauer Cuticle). Mutations in genes that affect the development and function of hypodermal cells result in defects in body morphogenesis, muscle development and cuticle structure and function. The mutants can produce  arrested embryos or larvae and adults with dumpy (dpy) and roller (rol) phenotypes (Kramer, 1997; Fay et al., 1999; see also The Cuticle).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1014, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "27ccd37a-a4f2-48d0-99c6-c63cd74b6df5": {"__data__": {"id_": "27ccd37a-a4f2-48d0-99c6-c63cd74b6df5", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Hypodermis, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/hypodermis/Hypframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cae73b40-72f6-44c6-8e9a-85b73e49613d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Hypodermis, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/hypodermis/Hypframeset.html)"}, "hash": "219b55eb06cea5d7c97ab50eb52f1c0908a7bfa7b9cba6c8be9303900788fdd9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Specialized epithelial cells, fall into three categories: (1) seam cells, which are also referred to as the lateral hypodermis (see Seam Cells); (2) interfacial epithelial cells, which are specialized linker cells located at the interface between hypodermis and another type of tissue (see Interfacial Cells); and (3) atypical epithelial cells, which include the XXX cells in the head and the tail spike cells, both of which have transient epithelial roles in embryonic development (see Atypical Cells).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 503, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "941ee0d4-7718-4b46-997c-ef2eb99d9038": {"__data__": {"id_": "941ee0d4-7718-4b46-997c-ef2eb99d9038", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Hypodermis, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/hypodermis/Hypframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "768563be-0808-4a75-8b45-048f805edd36", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Hypodermis, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/hypodermis/Hypframeset.html)"}, "hash": "0a7e06ec82bb98505b36e491c04b7f36d8c57638082565973d394ff312dd3469", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Epithelial cells of C. elegans are tightly held together by zonula adherens (formerly known as belt desmosomes) on their lateral borders, close to the apical surfaces. These junctions wrap around the epithelial cells and provide a seal and a mechanical link to the adjacent cells. They also segregate each cell membrane into two distinct regions: apical and basolateral surfaces (White, 1988; Michaux et al., 2001). In C. elegans, these junctions exhibit features of both adherens and tight junctions (Costa et al., 1998; Bossinger et al., 2001). The apical surfaces of the epithelial cells are bounded by the cuticle, and the basal surfaces are covered by the basal lamina.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 674, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6b525580-f3fa-4a53-bc8f-2c424a4224e5": {"__data__": {"id_": "6b525580-f3fa-4a53-bc8f-2c424a4224e5", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Hypodermis, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/hypodermis/Hypframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ad90fb73-dfff-4cbf-a03e-9a63153d1b07", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Hypodermis, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/hypodermis/Hypframeset.html)"}, "hash": "1483461655de23dedd645fda871c4876eddd0f1d80deecd39abaab571860f752", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The hypodermis and seam cells form multinucleate syncytia that are generated by cell fusions during development (HypTABLE 1). These cell fusions are regulated by diverse signaling mechanisms (Witze and Rothman, 2002; Podbilewicz, 2006).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 236, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "faf639fd-c51a-402a-a354-05c72bb512a4": {"__data__": {"id_": "faf639fd-c51a-402a-a354-05c72bb512a4", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Hypodermis, Section 2) Embryonic Development of the Hypodermis\n\t\t\t(also see (http://www.wormbook.org/chapters/www_epidermalmorphogenesis/epidermalmorphogenesis.html) in Wormbook)](https://www.wormatlas.org/hermaphrodite/hypodermis/Hypframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cdd58024-4deb-4e21-a813-984dee62e5fc", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Hypodermis, Section 2) Embryonic Development of the Hypodermis\n\t\t\t(also see (http://www.wormbook.org/chapters/www_epidermalmorphogenesis/epidermalmorphogenesis.html) in Wormbook)](https://www.wormatlas.org/hermaphrodite/hypodermis/Hypframeset.html)"}, "hash": "e834065db96b20ac9757f836c0206a8af2dea242aec756c2295d6666c6cb354e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "As in other triploblastic animals, the outer epithelium of C. elegans arises from the ectoderm. This tissue in C. elegans was originally named the hypodermis, although, in more recent literature it is sometimes referred to as the epidermis due to its ectodermal origin (Sulston and Horvitz, 1977; Wright, 1987). For practical purposes, we refer to it as hypodermis, because each hypodermal cell in C. elegans carries the three-letter acronym \u00e2\u0080\u009chyp.\u00e2\u0080\u009d The hypodermis develops largely from three cell types: embryonically from the AB founder cell and postembryonically from the lateral seam cells and the ventral blast (P) cells. In the embryo, the hypodermis becomes a monolayer of 78 epithelial cells that secrete the cuticle (Sulston et al., 1983). The majority of the hypodermis is generated from the AB founder cell, which has an intrinsic ability to produce hypodermis and neurons. During the third round of AB division, the potential to generate hypodermis is nonequivalently restricted to four daughter cells of the AB granddaughter cells (the posterior two granddaughters of ABa and the anterior two granddaughters of ABp), whereas their sisters primarily become neuronal precursors (HypFIG 1). Of the four AB great-granddaughters, ABalp is later induced by the MS cell to generate the pharynx, whereas the others continue with their major hypodermal fate (Cowan and McIntosh, 1985; Gendreau et al., 1994).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1415, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "dcafd4d6-c332-4fda-a29c-163d57def03b": {"__data__": {"id_": "dcafd4d6-c332-4fda-a29c-163d57def03b", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Hypodermis, Section 2) Embryonic Development of the Hypodermis\n\t\t\t(also see (http://www.wormbook.org/chapters/www_epidermalmorphogenesis/epidermalmorphogenesis.html) in Wormbook)](https://www.wormatlas.org/hermaphrodite/hypodermis/Hypframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f7f13c40-67f0-48e9-8083-870c842f3e6f", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Hypodermis, Section 2) Embryonic Development of the Hypodermis\n\t\t\t(also see (http://www.wormbook.org/chapters/www_epidermalmorphogenesis/epidermalmorphogenesis.html) in Wormbook)](https://www.wormatlas.org/hermaphrodite/hypodermis/Hypframeset.html)"}, "hash": "a11d628c232c93789edccc7dc489a868dcd72e8908f735bb0989ac4cefcc6ce7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Most of the embryonic hypodermal cells are born around 210-240 minutes after first cleavage at 20-22\u00c2\u00b0C and form a posterior dorsal sheet of cells that is organized in six rows (HypFIG 2). This hypodermal sheet eventually spreads to wrap around the embryo until the ventral edges meet and form adherens junctions to close the embryo in a continuous hypodermal layer. The larger 58 cells of the initial dorsal layer of cells are organized in two inner, two middle and two outer rows with 20, 20 and18 cells, respectively, at about 250 minutes after the first cleavage. The remaining, smaller 20 cells (hyp 1-5, three cells of hyp 6, hyp 8-11) at the anterior and posterior will later form the hypodermis of the anterior head and the tail. Between 290 and 340 minutes, the two inner rows of the epithelial sheet migrate towards each other and intercalate to make a single row of cells (HypFIG 2) (Podbilewicz and White, 1994; Williams-Masson et al., 1998; Chisholm and Hardin, 2005; Chin-Sang and Chisholm, 2000; Shemer and Podbilewicz, 2000; Simske and Hardin, 2001). Dorsal intercalation is essential for successful elongation of the embryo at later stages, although it is not required for ventral enclosure or dorsal cell fusions (Heid et al., 2001). The alignment of cells causes a slight lengthening of the dorsal hypodermis relative to the lateral and ventral sides that causes a slight ventral bend in the body.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1416, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0bacef16-80b6-4b4f-b684-c1b2d5b1d167": {"__data__": {"id_": "0bacef16-80b6-4b4f-b684-c1b2d5b1d167", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Hypodermis, Section 2) Embryonic Development of the Hypodermis\n\t\t\t(also see (http://www.wormbook.org/chapters/www_epidermalmorphogenesis/epidermalmorphogenesis.html) in Wormbook)](https://www.wormatlas.org/hermaphrodite/hypodermis/Hypframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b22dd613-6649-4770-ba41-9a32a2e65fe0", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Hypodermis, Section 2) Embryonic Development of the Hypodermis\n\t\t\t(also see (http://www.wormbook.org/chapters/www_epidermalmorphogenesis/epidermalmorphogenesis.html) in Wormbook)](https://www.wormatlas.org/hermaphrodite/hypodermis/Hypframeset.html)"}, "hash": "c6b67ee8ad12c0d493aa27fdfe91b7df4319bbf4b4ede84126615431d2bcc48a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "As dorsal intercalation nears completion, ventral enclosure begins (HypFIG 3). The enclosure of the ventral surface of the embryo involves a three-step process that leads to wrapping of the embryo in an epithelial monolayer (HypFIG 4A&B). In the initial step, two pairs of \u00e2\u0080\u009cleading cells\u00e2\u0080\u009d from the dorsolateral side elongate toward the ventral midline by extending actin-rich filopodia between the neuronal precursor cells underneath them. As these cells meet at the midline, the anterior pair of the leading cells is the first to establish stable adherens junctions, and eventually they fuse after enclosure to form part of the hyp 6 syncytium. The posterior pair also fuses and forms part of the hyp 7 syncytium. As the leading cells move toward the midline, the second step is initiated by the hypodermal cells that are posterior to the leading cells (the ventral pocket cells). These cells become wedge shaped and elongate toward the midline to form a \u00e2\u0080\u009cventral pocket\u00e2\u0080\u009d around the ventral midline. In the third step, this pocket is sealed, possibly by an actomyosin-dependent purse-string mechanism or by migration of its free edges (Williams-Masson et al., 1997; Simske and Hardin, 2001). If the proper organization of the substrate for migration of hypodermal cells does not occur during earlier stages of embryogenesis, ventral enclosure defects arise. One example of this is a failure in gastrulation cleft closure (George et al., 1998; Chin-Sang et al., 1999; Chin-Sang and Chisholm, 2000).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1506, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8cdbb2cd-6897-4f1b-938e-9f79bc187299": {"__data__": {"id_": "8cdbb2cd-6897-4f1b-938e-9f79bc187299", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Hypodermis, Section 2) Embryonic Development of the Hypodermis\n\t\t\t(also see (http://www.wormbook.org/chapters/www_epidermalmorphogenesis/epidermalmorphogenesis.html) in Wormbook)](https://www.wormatlas.org/hermaphrodite/hypodermis/Hypframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "69b0ff49-aba3-48d9-a782-feca363c29ac", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Hypodermis, Section 2) Embryonic Development of the Hypodermis\n\t\t\t(also see (http://www.wormbook.org/chapters/www_epidermalmorphogenesis/epidermalmorphogenesis.html) in Wormbook)](https://www.wormatlas.org/hermaphrodite/hypodermis/Hypframeset.html)"}, "hash": "d6b4ee1e118770e0e0ca67cded9751459ebff586c5740b0693ac9b3377504d1f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "After the ventral enclosure is completed, around 300-350 minutes after first cell cleavage at 20\u00c2\u00b0C, the embryo begins to elongate along its anterior-posterior axis (Priess and Hirsh, 1986; Simske and Hardin, 2001; Chisholm and Hardin, 2005). Apical surfaces of the hypodermal cells are squeezed circumferentially, resulting in pressure on internal structures and elongation of the whole embryo. Elongation causes the circumference of the animal to decrease threefold and its length to increase about fourfold (HypFIG 4C). As a result, the embryo changes from a lima-bean-like shape to a long, thin tube at threefold stage (see IntroFIG7). At the beginning of elongation, circumferential actin and tubulin filament bundles form in all hypodermal cells and are associated with the apical membranes. Actin filaments are anchored to adherens junctions at lateral cell margins via cadherin-catenin complexes. As elongation proceeds, actin filaments in the seam cells shorten (Costa et al., 1997; Costa et al., 1998; Priess and Hirsh, 1986). It has been suggested that the lateral hypodermal cells (seam cells) actively drive hypodermal elongation and that the contractile force that they generate is transmitted to the rest of the hypodermis via adherens junctions (Ding et al., 2004). Elongation proceeds at about 50 \u00ce\u00bcm/hr and is completed at around 600 minutes. The circumferential actin bundles disappear after elongation is complete (Priess and Hirsh, 1986; Costa et al., 1997). The integrity of the hypodermal sheet is essential for successful elongation; it is reinforced by the embryonic sheath, which is secreted over the surface of the embryo before elongation, and by microtubule bundles in dorsal and ventral hypodermal cells (Priess and Hirsh, 1986; Ding et al., 2004). These circumferentially organized microtubules probably distribute the force generated by actomyosin contraction. Intact muscle structure and attachments (fibrous organelles) that link muscle and hypodermis are required for continuation of the process in later stages of elongation. Mutants that show complete absence of muscle function fail to elongate beyond the twofold stage. Once elongation is completed, the embryo secretes a cuticle that maintains the body shape and replaces the embryonic sheath.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2283, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "47345969-9880-4727-8507-02bd6931c01e": {"__data__": {"id_": "47345969-9880-4727-8507-02bd6931c01e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Hypodermis, Section 2) Embryonic Development of the Hypodermis\n\t\t\t(also see (http://www.wormbook.org/chapters/www_epidermalmorphogenesis/epidermalmorphogenesis.html) in Wormbook)](https://www.wormatlas.org/hermaphrodite/hypodermis/Hypframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cdce6d61-4f21-4a37-8d4d-182454d59b5b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Hypodermis, Section 2) Embryonic Development of the Hypodermis\n\t\t\t(also see (http://www.wormbook.org/chapters/www_epidermalmorphogenesis/epidermalmorphogenesis.html) in Wormbook)](https://www.wormatlas.org/hermaphrodite/hypodermis/Hypframeset.html)"}, "hash": "ecd44eab5c8406cb83acb2219f72bb7f7224eba9ff21eb70a668640c42e7e57f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The hypodermal syncytia are formed by secondary cell fusions in the embryo, most of which take place as the embryos elongate (Podbilewicz and White, 1994; Podbilewicz, 2000, 2006). These cell fusions generally follow an order, although it can vary (Mohler et al., 1998). Fusion between cells takes place by two sequential processes; initial formation of a pore and expansion of the opening by internalization of the fusing cell membranes (Mohler et al., 1998). As the embryo is enclosed ventrally, about 340 minutes after first cleavage (before comma stage), the first cell-to-cell fusion occurs between two anterior ventral cells to initiate formation of hyp 7 syncytium (HypTABLE 2) (Podbilewicz and White, 1994). Fusion events then progress towards the posterior part of the elongating embryo, followed by fusion of the dorsal and ventral syncytia (Singh and Sulston , 1978; Priess and Hirsh, 1986; Hedgecock et al., 1987). Thus, at hatching, a total of 23 cells have joined to make the hyp 7 syncytium that covers most of the dorsal surface and parts of the ventral surface of the head and the tail (HypFIG 5). The anterior ring of hyp 7 covers the area around the excretory canal, and another posterior ring covers the post-anal region. Between these two rings, hyp 7 syncytium is not cylindrical at this time because of the presence of a lateral row of seam cells and a ventral row of P cells on each side (HypFIG 5A). The hyp 6 syncytium is initially formed by two separate fusions that then join to make the annular hyp 6 during elongation phase of embryogenesis. At this time, hyp 6 is connected to hyp 5 and hyp 7 by adherens junctions (HypFIG 5D) (Sulston et al., 1983; Podbilewicz and White, 1994; Shemer and Podbilewicz, 2000). At the end of embryogenesis the hyp 6 ring contains four dorsal and two ventral nuclei, while the hyp 7 ring contains six ventral, two dorsal and fifteen dorsolateral nuclei (HypFig 5A). The hyp 5 syncytium forms after the left and right lateral hyp 5 cells migrate and fuse. The left and right ventral hyp 4 cells fuse to initiate formation of the hyp 4 syncytium. The two cells that make the hyp 10 syncytium in the tail fuse between 1.5-fold and threefold stages.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2207, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0aaeff80-f815-4065-b8e6-f1dde4474c5b": {"__data__": {"id_": "0aaeff80-f815-4065-b8e6-f1dde4474c5b", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Hypodermis, Section 3) Post-embryonic Development of the Hypodermis](https://www.wormatlas.org/hermaphrodite/hypodermis/Hypframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "82ad37f2-d8da-43ab-82ae-225c332cd989", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Hypodermis, Section 3) Post-embryonic Development of the Hypodermis](https://www.wormatlas.org/hermaphrodite/hypodermis/Hypframeset.html)"}, "hash": "98845b1358f916852b883a182a0e7aea165ed36f2aec8bc4bc168485740f9337", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "During larval development, the body of the animal grows significantly, without many changes in the ectodermal body plan. The hyp 7 syncytium, which covers most of the body, must increase in volume accordingly. The seam cells must also grow to adapt to the increasing body size. To accommodate this growth, an additional 116 cells are added to hyp 7 during postembryonic development from P- and seam-cell lineages and from hyp 6 (HypFIG 1B&C). The seam cells, excluding H0, undergo a stem-cell division at the beginning of each larval stage and contribute additional 98 nuclei to the hyp 7 syncytium (HypFIG 6, 7 & 8 ). Soon after they are born, the daughters of seam stem cells that will become part of hyp 7 endoreduplicate their DNA and become tetraploid (Hedgecock and White, 1985). In contrast, the embryonically derived hyp 7 nuclei remain diploid.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 853, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9b8f8578-e2bf-4e72-bc1b-bc773c305be1": {"__data__": {"id_": "9b8f8578-e2bf-4e72-bc1b-bc773c305be1", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Hypodermis, Section 3) Post-embryonic Development of the Hypodermis](https://www.wormatlas.org/hermaphrodite/hypodermis/Hypframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6029b8f1-389e-4540-a3fc-c28ca732dcd5", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Hypodermis, Section 3) Post-embryonic Development of the Hypodermis](https://www.wormatlas.org/hermaphrodite/hypodermis/Hypframeset.html)"}, "hash": "0859b449f717bcd46864f464555bda189072bd9d218d6a5a9994b3f19245026f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "At hatching, the 12 unfused ventral hypodermal cells (P1-P12) are positioned as two parallel rows, with each cell confronting its bilateral homolog along the ventral midline (HypFIG 5C&D). In L1, these cells interdigitate to form a single row of cells on the ventral side (HypFIG 9) (Sulston and Horvitz, 1977). P1-P12 ventral cells divide soon after this, and the anterior daughters detach from the epithelium and become neuroblasts (Sulston and Horvitz, 1977; Hedgecock et al, 1987). The posterior daughters of P1, P2 and P9-12 fuse with hyp 7 at the end of the L1 stage, whereas the posterior daughters of P3-P8 divide at the L3 stage to make 12 cells. Of these, the daughters of P3p, P4p, and  P8p fuse with hyp 7; the daughters of P5p, P6p and P7p become vulva precursor cells (HypFIG 1C).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 794, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c3cdbedb-b870-4de7-8cf1-310eca48585a": {"__data__": {"id_": "c3cdbedb-b870-4de7-8cf1-310eca48585a", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Hypodermis, Section 4) Adult Hypodermis](https://www.wormatlas.org/hermaphrodite/hypodermis/Hypframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "acdc6261-0d60-4b66-bffa-3ce14cddf361", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Hypodermis, Section 4) Adult Hypodermis](https://www.wormatlas.org/hermaphrodite/hypodermis/Hypframeset.html)"}, "hash": "e4a4a66123fbe64d2fcb6412cb003cd4550d892434e50bd26a1b21f279086635", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In adult C. elegans, the hypodermis is composed of the main body syncytium, hyp 7 and smaller hypodermal cells in the head and  the tail, numbered from hyp 1 to hyp 5 and hyp 8 to hyp 11 (also, hyp 13 in the male). In the adult, hyp 7 contains 139 nuclei and envelops the whole body, except for the extreme head and tail. The hypodermal cells of the head and tail are generated during embryogenesis and acquire no additional nuclei post-embryonically.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 451, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "afb02b3c-0945-4605-ae69-18bde71ca620": {"__data__": {"id_": "afb02b3c-0945-4605-ae69-18bde71ca620", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Hypodermis, Section 4) Adult Hypodermis](https://www.wormatlas.org/hermaphrodite/hypodermis/Hypframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6ebb8967-6d5e-4815-9fde-d1c9696fea11", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Hypodermis, Section 4) Adult Hypodermis](https://www.wormatlas.org/hermaphrodite/hypodermis/Hypframeset.html)"}, "hash": "38f49bc5dfebef4deb6077236d4958ca982eac27986e6f1ee601ed61f948842d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The lips anterior to the buccal cavity are covered by three narrow, concentric rings of hypodermal cells (hyp 1, hyp 2 and hyp 3), which serve to unite the outer hypodermis to the epithelial lining of the digestive tract (HypFIG 10 and HypFIG 11, InterFIG 1). hyp 1 forms the innermost ring encircling the tip of the lips and connects to the arcade cells of the buccal cavity. hyp 3 forms the outermost ring and connects to hyp 2 on the inside and hyp 4 on the outside. All five hypodermal cells of the anterior head are syncytial, containing two to three nuclei (HypTABLE 1). Because of their posterior translocation during embryogenesis, the structures of these cells are similar to the arcade cells, such that their cell bodies are situated posterior to the concentric rings and connected to them by thin cytoplasmic processes (InterFIG 2).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 843, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "33cf7188-bb88-419f-9d66-187b6acebb2b": {"__data__": {"id_": "33cf7188-bb88-419f-9d66-187b6acebb2b", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Hypodermis, Section 4) Adult Hypodermis](https://www.wormatlas.org/hermaphrodite/hypodermis/Hypframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0631180a-5670-4bfa-a01d-4f739a044cca", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Hypodermis, Section 4) Adult Hypodermis](https://www.wormatlas.org/hermaphrodite/hypodermis/Hypframeset.html)"}, "hash": "a1c47b8470c2b8ed8ff2858348f146eb74bf9629f46b502a879139f60d2efdf6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The four tail tip hypodermal cells, hyp 8-11, are generated in early embryogenesis. During the elongation phase, they acquire their characteristic tapered shapes. This tapered shape continues throughout all stages of the hermaphrodite; it transforms into a complex fan-like shape in mid-L4 stage in males (Nguyen et al., 1999). hyp 8-10 closely fit onto one another in a succeeding fashion to make up the anal hypodermal ridge, which stretches between the dorsorectal ganglion and tail tip (HypFIG 12). hyp 11 lies just above the anal hypodermal ridge, separated from it by a basal lamina. The nuclei of hyp 8-10 lie within the ridge towards the anterior of each cell, whereas the nucleus of hyp 11 is located asymmetrically on the dorsal left side. Adherens and gap junctions link the neighboring hypodermal cells of the tail (see also Gap Junctions). The neuronal processes that extend to the extreme tail tip either penetrate through (PVR, PDB, PHC) the hypodermal cells or run next to them (PLM, PLN, PVR, PHC), sharing a basal lamina (Nguyen et al., 1999). Behind the phasmid openings, this basal lamina eventually ends, and the extreme tail whip consists of closely packed hypodermal (hyp 9 and hyp 10) and neuronal processes (Nguyen et al., 1999).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1254, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fb622b94-a84d-45b6-a89e-a03e8a9fc3bd": {"__data__": {"id_": "fb622b94-a84d-45b6-a89e-a03e8a9fc3bd", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Hypodermis, Section 5) List of Hypodermal Cells](https://www.wormatlas.org/hermaphrodite/hypodermis/Hypframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f81902b3-8836-4549-853e-7a889bc1691f", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Hypodermis, Section 5) List of Hypodermal Cells](https://www.wormatlas.org/hermaphrodite/hypodermis/Hypframeset.html)"}, "hash": "a7c3c2178989a93f82134ab145dcb25080f5d3d7e9ff0910bf78382e02ed218b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "hyp 7 (LL40) - V5L.ppppp\n\nhyp 7 (LL45)\u00a0-\u00a0V6L.ppa\n\nhyp 7 (LL46)\u00a0-\u00a0V6L.ppppa\n\nhyp 7 (LL47)\u00a0-\u00a0TL.aa\n\nhyp 7 (LL48)\u00a0-\u00a0TL.apaa\n\nhyp 7 (LL49)\u00a0-\u00a0TL.apap\n\nhyp 7 (LR18)\u00a0-\u00a0V2R.pappa\n\nhyp 7 (LR19)\u00a0-\u00a0V2R.ppa\n\nhyp 7 (LR20)\u00a0-\u00a0V2R.pppa\n\nhyp 7 (LR21)\u00a0-\u00a0V2R.ppppa\n\nhyp 7 (LR22)\u00a0-\u00a0V3R.a\n\nhyp 7 (LR23)\u00a0-\u00a0V3R.paa\n\nhyp 7 (LR24)\u00a0-\u00a0V3R.papa\n\nhyp 7 (LR25)\u00a0-\u00a0V3R.pappa\n\nhyp 7 (LR26)\u00a0-\u00a0V3R.ppa\n\nhyp 7 (LR27)\u00a0-\u00a0V3R.pppa\n\nhyp 7 (LR28)\u00a0-\u00a0V3R.ppppa\n\nhyp 7 (LR29)\u00a0-\u00a0V4R.a\n\nhyp 7 (LR30)\u00a0-\u00a0V4R.paa\n\nhyp 7 (LR31)\u00a0-\u00a0V4R.papa\n\nhyp 7 (LR32)\u00a0-\u00a0V4R.pappa\n\nhyp 7 (LR33)\u00a0-\u00a0V4R.ppa\n\nhyp 7 (LR34)\u00a0-\u00a0V4R.pppa\n\nhyp 7 (LR35)\u00a0-\u00a0V4R.ppppa\n\nhyp 7 (LR36)\u00a0-\u00a0V5R.a\n\nhyp 7 (LR37)\u00a0-\u00a0V5R.ppa\n\nhyp 7 (LR38)\u00a0-\u00a0V5R.pppa\n\nhyp 7 (LR39)\u00a0-\u00a0V5R.ppppa\n\nhyp 7 (LR40)\u00a0-\u00a0V5R.ppppp\n\nhyp 7 (LR41)\u00a0-\u00a0V6R.a\n\nhyp 7 (LR42)\u00a0-\u00a0V6R.paa\n\nhyp 7 (LR43)\u00a0-\u00a0V6R.papa\n\nhyp 7 (LR44)\u00a0-\u00a0V6R.pappa\n\nhyp 7 (LR45)\u00a0-\u00a0V6R.ppa\n\nhyp 7 (LR46)-\u00a0V6R.ppppa\n\nhyp 7 (LR47)\u00a0-\u00a0TR.aa\n\nhyp 7 (LR48)\u00a0-\u00a0TR.apaa\n\nhyp 7 (LR49)\u00a0-\u00a0TR.apap\n\n3. Tail\u00a0(posterior to anus; all embryonic)\n\nhyp 7 (V22/23)\u00a0-\u00a0ABplappppa\u00a0(aka hyp 13)\n\nhyp 7 (V22/23)\u00a0-\u00a0ABprappppa\u00a0(aka hyp 13)\n\nhyp 8/9\u00a0-\u00a0ABplpppapap\n\nhyp 8/9\u00a0-\u00a0ABprpppapap\n\nhyp 10 (V1/2)\u00a0-\u00a0ABplppppppp\n\nhyp 10 (V1/2)\u00a0-\u00a0ABprppppppp\n\nhyp 11\u00a0-\u00a0Cpappv", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1177, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8a631ff1-3e7a-4050-b42a-43635f3e82a8": {"__data__": {"id_": "8a631ff1-3e7a-4050-b42a-43635f3e82a8", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Hypodermis, Section 5) List of Hypodermal Cells](https://www.wormatlas.org/hermaphrodite/hypodermis/Hypframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4858545c-64e3-49cb-b3ec-4c7bcc7d0a66", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Hypodermis, Section 5) List of Hypodermal Cells](https://www.wormatlas.org/hermaphrodite/hypodermis/Hypframeset.html)"}, "hash": "0e3ff1d67ac642273cd1aa3005b80fc89be3ef1fa250671d7d75a17fad2df997", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Entire hyp7 syncytium", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 21, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4b9cd7b2-744a-4af2-a376-6f0a8002bb80": {"__data__": {"id_": "4b9cd7b2-744a-4af2-a376-6f0a8002bb80", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Hypodermis, Section 6) References](https://www.wormatlas.org/hermaphrodite/hypodermis/Hypframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e355a70e-0f64-4f3b-875f-6534f02c9a85", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Hypodermis, Section 6) References](https://www.wormatlas.org/hermaphrodite/hypodermis/Hypframeset.html)"}, "hash": "c369f696213e890506815db402fd4bf4a3a447d99439d18434668bc0da19f99c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Chin-Sang, I.D., George, S.E., Ding, M., Moseley, S.L., Lynch, A.S. and Chisholm, A.D. 1999. The ephrin VAB-2/EFN-1 functions in neuronal signaling to regulate epidermal morphogenesis in C. elegans. Cell 99: 781-790. Article", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 224, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "922883ab-3995-4fee-bb84-7ec0f006d5f5": {"__data__": {"id_": "922883ab-3995-4fee-bb84-7ec0f006d5f5", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Germ Line, Section 1) General Description](https://www.wormatlas.org/hermaphrodite/germ line/Germframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2002903b-1a93-47ae-8e90-bbac5cdf48b0", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Germ Line, Section 1) General Description](https://www.wormatlas.org/hermaphrodite/germ line/Germframeset.html)"}, "hash": "8618ff6924fe710104f311fe5d8d1f70ffd69d4484bddbee01b8b38aa3fbb04e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The hermaphrodite germ line produces both male and female gametes\u00e2\u0080\u0094sperm and oocytes, respectively (see Germline Section in WormBook, Sperm Gallery). Oocytes are produced throughout adult life; sperm (spermatozoa) are generated during L4 and then used in adulthood to fertilize oocytes. The adult germ line exhibits distal\u00e2\u0080\u0093proximal polarity, with a mitotic cell population located at the distalmost end of the gonad and meiotic cells, extending proximally. Among the meiotic cells is also a gradient of meiotic progression with successive stages of meiosis I prophase extending from the distal arm, around the loop into the proximal arm of the gonad. Gametogenesis occurs in the proximal part of the gonad arm (GermFIG 1).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 725, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6600fbb7-238b-4c8e-9379-47d5500e6537": {"__data__": {"id_": "6600fbb7-238b-4c8e-9379-47d5500e6537", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Germ Line, Section 1) General Description](https://www.wormatlas.org/hermaphrodite/germ line/Germframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f6c8373a-ae08-4a18-8ea4-b7871b9bcadb", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Germ Line, Section 1) General Description](https://www.wormatlas.org/hermaphrodite/germ line/Germframeset.html)"}, "hash": "f7776a05c60a13252fc13942c1234e06edd824bc957e574eb068e7941a9e8e17", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The distal germ line is a syncytium. Germ cells have incomplete borders and are connected to one another via a central canal called the rachis (GermFIG 1 and GermFIG 2) (Hirsh et al., 1976). Part of the distal gonad is not covered by the somatic tissues (the \u00e2\u0080\u009cbare region\u00e2\u0080\u009d) and is instead ensheathed only by the gonadal basal lamina (GBL) that covers the rest of the gonad (SomaticFIG 2C) (see Reproductive System - Somatic Gonad; Hall et al., 1999). At the base of each germ cell, and covering the rachis, is a thickened extracellular matrix. This matrix contains hemicentin and is thought to reinforce and stabilize the opening of the germ cells to the rachis (GermFIG 2B; Pericellular Structures) (Vogel and Hedgecock, 2001). The end point of the rachis may differ as the animal ages. For example, in young adults, the rachis terminates within the proximal gonad, just past the loop; in older adults, the rachis terminates in the distal gonad, although still near the loop (McCarter et al., 1997). Oocytes may retain a vestigial connection to the rachis even after moving well past its apparent end point (J. White, pers. comm.), so that a maturing oocyte in the proximal arm might retain a thin, cryptic arm reaching through the loop to the distal rachis.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1263, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "140907c6-e579-44f4-bf0e-ab1fc8ec1eff": {"__data__": {"id_": "140907c6-e579-44f4-bf0e-ab1fc8ec1eff", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Germ Line, Section 2) Mitosis and Meiosis in the Germ Line](https://www.wormatlas.org/hermaphrodite/germ line/Germframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4d324372-d6b1-4d11-a411-b600fc0f676b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Germ Line, Section 2) Mitosis and Meiosis in the Germ Line](https://www.wormatlas.org/hermaphrodite/germ line/Germframeset.html)"}, "hash": "a769508b73e928aaafd4ccd7ae7cf08808591f78be172a995e940aac911233c0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The distalmost end of the adult gonad, referred to as the mitotic zone, contains a stem-cell population. As germ cells move away from the influence of the DTC (see Reprodutive System - Somatic Gonad), they enter meiosis I and then proceed through prophase I to diakinesis (GermFIG 3A\u00e2\u0080\u0093E) (Hirsh et al., 1976; reviewed in Hubbard and Greenstein, 2000; Hansen et al., 2004).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 373, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ccbbd345-abea-4b23-b5ca-dcbde37d129b": {"__data__": {"id_": "ccbbd345-abea-4b23-b5ca-dcbde37d129b", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Germ Line, Section 2) Mitosis and Meiosis in the Germ Line](https://www.wormatlas.org/hermaphrodite/germ line/Germframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9900cef5-35a2-4899-8776-f7b2193c9b3c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Germ Line, Section 2) Mitosis and Meiosis in the Germ Line](https://www.wormatlas.org/hermaphrodite/germ line/Germframeset.html)"}, "hash": "f88b6b2be08eb0d5cc2ec9df08bfb48a0375f135a008fa0f717e14c08f946de5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The mitotic zone of the adult is approximately 20 cell diameters in length, extending from the DTC to the transition zone (GermFIG 3A) (described below; Crittenden et al., 1994). With DAPI staining at the level of light microscopy, M-phase nuclei can be distinguished from the rest of the cell cycle: Nuclei are relatively uniform and, at any given time, have a hazy fluorescence in the center and brighter circumferential staining. Condensed chromatin appears as nuclei enter prometaphase. The average number of M-phase nuclei visible in any given mitotic zone in the adult is low, about two nuclei per arm (J. Maciejowski and E.J. Hubbard, pers. comm.). At the level of electron microscopy, mitotic germ cells are uniform in size and appearance (GermFIG 2). Each cell is roughly cuboidal, with a large nucleus. The cytoplasm contains a few mitochondria, limited rough endoplasmic reticulum (RER), and few free ribosomes. The rachis itself is also filled with RER and ribosomes, but  contains more mitochondria. The transition zone is characterized by germ cells entering the early phases of meiotic prophase (leptotene and zygotene) and is defined as the area between the distalmost transition nucleus and the proximalmost transition nucleus (Hansen et al., 2004). A change in the nuclear morphology can be shown with DAPI: Nuclei are condensed and crescent-shaped (GermFIG 3D).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1380, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cfb283de-44cd-478e-9674-07a2e93a96c5": {"__data__": {"id_": "cfb283de-44cd-478e-9674-07a2e93a96c5", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Germ Line, Section 2) Mitosis and Meiosis in the Germ Line](https://www.wormatlas.org/hermaphrodite/germ line/Germframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bc0b9fb9-29d4-4103-a4d4-ba736f7c00a1", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Germ Line, Section 2) Mitosis and Meiosis in the Germ Line](https://www.wormatlas.org/hermaphrodite/germ line/Germframeset.html)"}, "hash": "d0575c29f321b330eaed3cf01df8a6696d2fc17a19455b21c41bebef6875f8e8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "After moving through the transition zone, germ cells progress into pachytene and gradually grow. Pachytene nuclei are characterized by a distinctive \u00e2\u0080\u009cbowl of spaghetti\u00e2\u0080\u009d morphology as homologous chromosomes start to align side by side (GermFIG 3C). Exit from pachytene requires activation of a MAPK (MAP kinase) pathway, thought to be triggered by a signal from the overlying gonadal sheath (Church et al., 1995; McCarter et al., 1997). Progression of nuclei into diplotene occurs in the loop and cells become organized in single file as they enter the proximal arm (GermFIG 3).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 581, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f7004be8-d6bf-4395-a083-41a3f7dad25b": {"__data__": {"id_": "f7004be8-d6bf-4395-a083-41a3f7dad25b", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Germ Line, Section 3) Germ-line Programmed Cell Deaths](https://www.wormatlas.org/hermaphrodite/germ line/Germframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "82d713d9-d008-4cbf-a259-4053b6aa1a83", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Germ Line, Section 3) Germ-line Programmed Cell Deaths](https://www.wormatlas.org/hermaphrodite/germ line/Germframeset.html)"}, "hash": "9116f4b34fd47ed3c4b107602e3081ed24da2ed3eb0a99a2d322f683305c1942", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In addition to oocyte and sperm fate, programmed cell death (PCD) represents a major cell fate among adult germ cells. It is estimated that approximately one half of all potential oocytes are eliminated in the adult hermaphrodite during progression through prophase of meiosis I. Most cell deaths occur near the loop region of the gonad arm, the region containing pachytene-stage germ cells (see GermFIG 3A,C). It has been proposed that these excess germ cells may serve as a nurse cell population, providing proteins and other cytoplasmic components to surviving germ cells (Hengartner, 1997). Electron and light microscopy analyses of dying cells reveal that cell deaths occur by apoptosis (GermFIG 4A\u00e2\u0080\u0093C) (Gumienny et al., 1999). As in somatic tissues, cell death execution depends on ced-3, ced-4, and ced-9 function. However, genetic evidence also suggests that somatic and germ cell death mechanisms may not be entirely identical (Hengartner et al., 1992; Gumienny et al., 1999). Overlying gonadal sheath cells (likely sheath-cell pair 2) engulf cell death corpses (Gumienny et al., 1999).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1096, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4666ac0b-791a-42e2-a423-5dc948518b90": {"__data__": {"id_": "4666ac0b-791a-42e2-a423-5dc948518b90", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Germ Line, Section 4) Oocyte Maturation, Ovulation and Fertilization](https://www.wormatlas.org/hermaphrodite/germ line/Germframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a035de65-de36-492b-b075-d2f4dd1fc503", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Germ Line, Section 4) Oocyte Maturation, Ovulation and Fertilization](https://www.wormatlas.org/hermaphrodite/germ line/Germframeset.html)"}, "hash": "d7d309aebf8089fba83fa31f676accc99a2308466d0f319d930a42d40364861d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Oocyte maturation takes place in the oocyte closest to the spermatheca, just before ovulation, and is stimulated by sperm-derived major sperm protein (MSP) (GermFIG 5) (Miller et al., 2001). During maturation, nuclear envelope breakdown (NEBD; also known as germinal vesicle breakdown) occurs, the nucleus becomes less obvious, and cortical rearrangements cause the oocyte to become more spherical. Chromosome arrangement changes as bivalent chromosomes leave diakinesis and begin to align onto the metaphase plate (Ward and Carrel, 1979; McCarter et al., 1999).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 562, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e022831a-fea9-41ca-ac82-7374f7500eeb": {"__data__": {"id_": "e022831a-fea9-41ca-ac82-7374f7500eeb", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Germ Line, Section 4) Oocyte Maturation, Ovulation and Fertilization](https://www.wormatlas.org/hermaphrodite/germ line/Germframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "afb6ab3e-8936-4215-8453-41f6af8145e0", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Germ Line, Section 4) Oocyte Maturation, Ovulation and Fertilization](https://www.wormatlas.org/hermaphrodite/germ line/Germframeset.html)"}, "hash": "d6f7f0c0332e21808f3c5815d8e62e1a493a626c597f1690d983f6c6eee2ebdd", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Ovulation follows oocyte maturation. Signals from the maturing oocyte and MSP stimulate the rate and intensity of sheath contraction from a basal rate of 10\u00e2\u0080\u009313 contractions/minute to approximately 19 contractions/minute (McCarter et al., 1999; Miller et al., 2001, 2003). Oocyte maturation also stimulates distal spermathecal dilation through LIN-3/LET-23 RTK pathway activation and IP3 signaling (Clandinin et al., 1998; McCarter et al., 1999; Bui and Sternberg, 2002). The dilated spermatheca is pulled over the oocyte by the contracting sheath, and the spermatheca then closes. The oocyte is immediately penetrated by a sperm and fertilized. Cell\u00e2\u0080\u0093cell recognition between gametes during this process is mediated by SPE-9, a sperm-specific, epidermal growth factor (EGF)-repeat-containing transmembrane protein (Singson et al., 1998). Cytoplasmic streaming in the oocyte accompanies fertilization, meiosis is completed, and eggshell secretion commences (Ward and Carrel, 1979; Singson, 2001). The newly formed embryo then passes from the spermatheca to the uterus via the spermathecal-uterine valve.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1105, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5156a726-2a3c-441c-9b0e-961f139d220a": {"__data__": {"id_": "5156a726-2a3c-441c-9b0e-961f139d220a", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Germ Line, Section 5) Germ-line Development](https://www.wormatlas.org/hermaphrodite/germ line/Germframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2aee6ea6-d043-4e07-9772-7203b30a841a", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Germ Line, Section 5) Germ-line Development](https://www.wormatlas.org/hermaphrodite/germ line/Germframeset.html)"}, "hash": "8cad55772f13fa9bb880f587d79c11155192b8d8f1709eb441667815c30581ed", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Germ-line development spans L1 to early adulthood (GermFIG 6; GermMOVIE 1). All germ cells are descended from either Z2 or Z3 (Schedl, 1997; Hubbard and Greenstein, 2000). In contrast to somatic lineage development, germ-line cell divisions appear to be variable with respect to their timing and planes of division, and hence the precise lineal relationships between these cells are not known (Kimble and Hirsh, 1979). In L4, approximately 37 meiotic cells per arm at the most proximal end of the germ line commit to sperm development. Subsequently, the germ line switches from making sperm to making oocytes for the remainder of development and throughout adulthood. This switch between male and female cell fate results from germ-line modulation of sex determination pathway activity (Kuwabara and Perry, 2001). Germ-line development depends on interactions with the overlying somatic gonad. Somatic gonad cells, or their precursors, affect the timing and position of the germ-line mitosis/meiosis decision, and they exit from pachytene, gametogenesis, and male gamete fate during germ-line sex determination (Kimble and White, 1981; Seydoux et al., 1990; McCarter et al., 1997; Rose et al., 1997; Pepper et al., 2003; Killian and Hubbard, 2004).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1248, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e65620a6-d7ba-491b-b633-d8c995283026": {"__data__": {"id_": "e65620a6-d7ba-491b-b633-d8c995283026", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Germ Line, Section See) <a href=\"https://www.wormatlas.org/Wardsperm/sperm.htm\" target=\"_blank\">Sperm Gallery</a> for detailed pictures and videos](https://www.wormatlas.org/hermaphrodite/germ line/Germframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0947ff4e-0848-413f-8557-ff0d79eeacd7", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Germ Line, Section See) <a href=\"https://www.wormatlas.org/Wardsperm/sperm.htm\" target=\"_blank\">Sperm Gallery</a> for detailed pictures and videos](https://www.wormatlas.org/hermaphrodite/germ line/Germframeset.html)"}, "hash": "75a37dcf9847970310a884480cb0ad35ababe3ca1cd5ac6a19b39d7a3cbc442a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The germ line of each gonad arm produces about 150 sperm during L4 (GermFIG 6 and GermFIG 7A) (L\u00e2\u0080\u0099Hernault, 1997). Approximately 37 diploid germ cells per gonad arm form primary spermatocytes while still attached to the rachis. After pachytene, spermatocytes detach from the rachis and complete meiosis, generating haploid spermatids. This process of spermatid formation is called spermatogenesis (GermFIG 7B, C&D) (Ward et al., 1981).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 436, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0594923c-7cff-4064-ac4c-b78de31a087d": {"__data__": {"id_": "0594923c-7cff-4064-ac4c-b78de31a087d", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Germ Line, Section See) <a href=\"https://www.wormatlas.org/Wardsperm/sperm.htm\" target=\"_blank\">Sperm Gallery</a> for detailed pictures and videos](https://www.wormatlas.org/hermaphrodite/germ line/Germframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6067a6df-8c35-4b76-bc9c-2d569d98ba99", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Germ Line, Section See) <a href=\"https://www.wormatlas.org/Wardsperm/sperm.htm\" target=\"_blank\">Sperm Gallery</a> for detailed pictures and videos](https://www.wormatlas.org/hermaphrodite/germ line/Germframeset.html)"}, "hash": "96c28a6cbc0e46944334bbc15183e3866b0e173785136592430a8db4145ad64d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Developing spermatocytes contain a large number of specialized vesicles called fibrous body-membranous organelles (FB-MOs) (GermFIG8 A&B and GermFIG 9A). These organelles contain proteins required in the future spermatids and spermatozoa, including MSP (Ward and Klass, 1982). During development, the FB-MOs partition with the portion of the spermatocyte destined to become the future spermatid (Ward, 1986). The residual body (GermFIG 7B&7D, Budding Spermatids Figure) acts as a deposit area for proteins and organelles no longer required by the developing spermatid (L\u00e2\u0080\u0099Hernault, 1997; Arduengo et al., 1998; Kelleher et al., 2000).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 635, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "486b8803-e53a-41fb-8196-f91e6fd3b2a9": {"__data__": {"id_": "486b8803-e53a-41fb-8196-f91e6fd3b2a9", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Germ Line, Section See) <a href=\"https://www.wormatlas.org/Wardsperm/sperm.htm\" target=\"_blank\">Sperm Gallery</a> for detailed pictures and videos](https://www.wormatlas.org/hermaphrodite/germ line/Germframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b4a2ff3e-648e-45aa-bd17-b46785dce37a", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Germ Line, Section See) <a href=\"https://www.wormatlas.org/Wardsperm/sperm.htm\" target=\"_blank\">Sperm Gallery</a> for detailed pictures and videos](https://www.wormatlas.org/hermaphrodite/germ line/Germframeset.html)"}, "hash": "168dc771014babe4b30ff3c8e942c279fde45d31f0f43d94a27d44ce211e27a5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Spermatogenesis takes place within the proximal gonad (GermFIG 7B). The formed spermatids are pushed into the spermatheca by the first oocyte during the first ovulation. In the spermatheca, an unknown signal induces these sessile spermatids to undergo morphogenesis into mature, amoeboid spermatozoa (sperm) (cf. GermFIG 9B&C, Spermatozoon SEM and TEM) (Nelson and Ward, 1980; Ward et al., 1983). This process of activation is known as spermiogenesis (See Spermiogenesis Figure and Video in Sperm Gallery).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 506, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "705d3620-595e-4ce4-a175-fbae89aee78c": {"__data__": {"id_": "705d3620-595e-4ce4-a175-fbae89aee78c", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Germ Line, Section See) <a href=\"https://www.wormatlas.org/Wardsperm/sperm.htm\" target=\"_blank\">Sperm Gallery</a> for detailed pictures and videos](https://www.wormatlas.org/hermaphrodite/germ line/Germframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4cfa48bd-a91d-4b92-ab61-9e6fff39c585", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Germ Line, Section See) <a href=\"https://www.wormatlas.org/Wardsperm/sperm.htm\" target=\"_blank\">Sperm Gallery</a> for detailed pictures and videos](https://www.wormatlas.org/hermaphrodite/germ line/Germframeset.html)"}, "hash": "6a76992bbfeabe9d57451cc80d952107a1c6f1df9a79c58ce8d6a1da8a7ed6d8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Maturing spermatids and spermatozoa have highly condensed nuclei and tightly packed mitochondria (GermFIG 9B&C, Spermatozoon TEM Figure). In spermatids, MOs (now lacking the FB) locate near the cell periphery (GermFIG 9B). During spermatid activation, MOs fuse with the plasma membrane, releasing their contents (primarily glycoproteins) onto the cell surface. A fusion pore is generated on the cell surface by the MO collar (GermFIG 9C). Mutants affected in MO fusion produce sperm with defective motility, suggesting that MO content enhances sperm mobility (Ward et al., 1981; Roberts et al., 1986; Achanzar and Ward, 1997). Unlike sperm in many other animal phyla, C. elegans sperm are not flagellated. Rather, spermatid activation involves the formation of a foot or pseudopodium that allows the spermatozoon to attach to the walls of the spermathecal lumen and to crawl by projecting from and dragging the cell body (see Sperm Crawling and Treadmilling Videos). This motility is driven by dynamic polymerization of MSP, which, in addition to containing sequences that mediate extracellular signaling (described above; Miller et al., 2001), has an intracellular cytoskeletal function (Italiano et al., 1996; Roberts and Stewart, 2000).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1239, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "bd7537a7-4dea-4884-9bfb-713174b1d6a1": {"__data__": {"id_": "bd7537a7-4dea-4884-9bfb-713174b1d6a1", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [GLR Cells, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/muscleGLR/MusGLRframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7ee09302-db16-456e-b9ab-54d110d60529", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [GLR Cells, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/muscleGLR/MusGLRframeset.html)"}, "hash": "8b54f7c3c2f34391e5026564336162fb3f7958f40f270a2de0d5a0a512f1592a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Three pairs of GLR cells (GLRDL/R, GLRL/R, GLRVL/R) lie within the pseudocoelom at the level of the pharyngeal isthmus, slightly posterior to the nerve ring (GlrFIG 1). They are arranged in a sixfold symmetrical manner (GlrFIG 2). The cell bodies of the GLRs lie near the dorsal and ventral insertions of the muscle arms of the head, where the muscle arms enlarge to dive toward the isthmus of the pharynx. This close physical proximity may reflect the common lineage of the GLRs and the body wall muscles because both derive from the MS lineage. Their sister cells also include the head mesodermal cell, the pharyngeal musculature, and the coelomocytes (For more information see sections for: Head Mesomdermal Cell, Nonstriated Muscle, Coelomocytes).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 751, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "59d8a568-9c0a-427d-8ebe-bddc7f4868fe": {"__data__": {"id_": "59d8a568-9c0a-427d-8ebe-bddc7f4868fe", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [GLR Cells, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/muscleGLR/MusGLRframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "93e5d81e-59d2-4c99-a1ba-b9a42d721621", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [GLR Cells, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/muscleGLR/MusGLRframeset.html)"}, "hash": "333d76beb1c16b8a82e61a5bb89b5801bfd809f226df0d43f36bc18a27bb71a9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "All six GLR cell somata lie posteriorly to the nerve ring, and their positioning reflects the tilt of the nerve ring. The pronounced medial turn of each head muscle arm occurs in close apposition to GLR cell bodies. Anteriorly, each GLR cell extends a thin, sheet-like process (GlrFIG 2B). On the outside, these processes are surrounded by the muscle plate that lies inside the motor end plate layer of the nerve ring, where muscles receive synaptic input from the nerve ring motor neurons (GlrFIG 2 and GlrFIG 3). Each of these processes wraps around roughly one third of the circumference of the isthmus, touching its neighbor on each side (GlrFIG 4, GlrFIG 5 and GlrFIG 3H). There is no direct connection of the GLRs to the pharyngeal basement membrane, which lies between the GLR cells and the pharynx, and there is no basement membrane separating the muscle arms from the GLR processes (White et al., 1986). Arms from each of the eight longitudinal rows of the head muscles run along specific GLR cells such that each GLRDL/R and GLRVL/R is associated with muscle arms from a single row and each GLRL and GLRR is associated with muscle arms from two rows. Gap junctions exist between GLR cells and the muscle arms and between GLRs and RME motor neurons (see Gap Junctions). However, GLR cells do not make gap junctions to one another nor are they involved in any chemical synapses.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1386, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9c849f3f-9653-4df4-95f9-669358c03ac2": {"__data__": {"id_": "9c849f3f-9653-4df4-95f9-669358c03ac2", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [GLR Cells, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/muscleGLR/MusGLRframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c4e37224-0c8b-445c-8a77-5a8f49b854ad", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [GLR Cells, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/muscleGLR/MusGLRframeset.html)"}, "hash": "caa5bbbf464e1c08e07ba6faee0fc63697bc79dd5129f239d0f4e5405cb35e03", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Anterior to the nerve ring, GLR processes narrow down into thin processes and continue anteriorly to peter out at the level of the junction of the pharynx and the buccal cavity without any terminal specializations (GlrFIG 2 and GlrFIG 3). Throughout their length, the anterior GLR processes run in the inner labial bundles, closely apposed to the IL1 dendrites.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 361, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1471b1be-3c8a-477b-b2bc-0369e93ff164": {"__data__": {"id_": "1471b1be-3c8a-477b-b2bc-0369e93ff164", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [GLR Cells, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/muscleGLR/MusGLRframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3fc64ef6-c01a-4a01-81a3-c2e396a3ff63", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [GLR Cells, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/muscleGLR/MusGLRframeset.html)"}, "hash": "e615860d88afdc4b43544e0d992d79712f2fc2c2ff0374e1873660be3118af76", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The cytoplasm of the GLR cell body is electron dense and contains a distinctive collection of membrane-bound vacuoles. With TEM, these vacuoles formally look very similar to inclusions in the distal tip cells and the coelomocytes. This suggests an active endocytic or secretory function for GLRs.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 296, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "631b268d-4012-4680-9878-647271908d52": {"__data__": {"id_": "631b268d-4012-4680-9878-647271908d52", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [GLR Cells, Section 2) Function of GLR Cells](https://www.wormatlas.org/hermaphrodite/muscleGLR/MusGLRframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e30fc42d-9eee-46f1-b945-54f8794d5349", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [GLR Cells, Section 2) Function of GLR Cells](https://www.wormatlas.org/hermaphrodite/muscleGLR/MusGLRframeset.html)"}, "hash": "0c0ae55a4f9b799ea81146dd39bf3562c3ef6285dcdb6e2c15c79f6f1fa01830", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Because of their location, connectivity pattern, and lineage, GLR cells are suggested to be mesodermal scaffolding cells that guide muscle arms to appropriate territories during development (White et al., 1986). The C. elegans myoD homolog hlh-1, which is expressed by lineal precursors of body wall muscle and is required for normal muscle function, is also expressed in GLR cells in late embryogenesis and larval stages. It has been suggested that hlh-1 might drive expression of cell-surface proteins that mediate recognition and contact between GLRs and head muscles (Krause et al., 1994). Similar to body wall muscle cells, GLR cells secrete type IV collagen, which is integrated into the basement membrane underlying the muscle (Graham et al., 1997; Norman and Moerman, 2000).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 782, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "34c95906-2d2c-4659-b4a4-0400cb8ddbc8": {"__data__": {"id_": "34c95906-2d2c-4659-b4a4-0400cb8ddbc8", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [GLR Cells, Section 2) Function of GLR Cells](https://www.wormatlas.org/hermaphrodite/muscleGLR/MusGLRframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cbda74e8-552c-43df-8956-8d1a2d600756", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [GLR Cells, Section 2) Function of GLR Cells](https://www.wormatlas.org/hermaphrodite/muscleGLR/MusGLRframeset.html)"}, "hash": "e86b46497ae8f6cbabd42e752c5b78c3ffa6167d45f4312d0403ed3ef3b05464", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "At the anterior end of the nerve ring, the sheet-like anterior processes of GLRs briefly seal the space between the end of the somatic basement membrane of the muscle and the basement membrane of the pharynx and the pseudocoelom. Hence, anterior to this region, the narrow space between the pharynx and outer tissues is designated as an accessory pseudocoelom (see Pericellular Structures) (Z. Altun and D.H. Hall, unpubl.). It is not yet clear if there is material exchange between these two spaces. When any one of the parental cells of the GLRs (MSaaaaaa for GLRDL/R; MSapaaaa for GRLL/VL;  MSppaaaa for GLRR/VR) is killed in the embryo, the worms hatch late and arrest as starved L1-stage animals. In these animals, nerve rings are displaced anteriorly and there is widespread degeneration and vacuolation in neurons and hypodermis, which may result from disruption of the GLR seal (A. Chisholm, pers. comm.).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 913, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7a0f8b5a-fa19-479f-8a5e-30ec894d5d72": {"__data__": {"id_": "7a0f8b5a-fa19-479f-8a5e-30ec894d5d72", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Head Mesodermal Cell, Section 1) Head Mesodermal Cell](https://www.wormatlas.org/hermaphrodite/muscleheadcell/Mushmcframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fb9757d9-6b2e-4049-9b5c-93d91f760b55", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Head Mesodermal Cell, Section 1) Head Mesodermal Cell](https://www.wormatlas.org/hermaphrodite/muscleheadcell/Mushmcframeset.html)"}, "hash": "f36f31820d47b6bb0012f2c2c0c15ea6b1f4d180fa3e5134a600cbf52eceae55", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The head mesodermal cell (hmc) and its homolog originate from the embryonic MS lineage and are sisters of gonadal cells Z4 and Z1, respectively (HmcFIG 1; Sulston et al., 1983). This single cell in the head lies in the pseudocoelom on the dorsal posterior side of the pharynx (HmcFIG 2). In the embryo, the hmc and hmc homolog migrate circumferentially to the dorsal midline where they meet and align anterior\u00e2\u0080\u0093posteriorly. The more anteriorly located cell (hmc homolog) dies late in embryogenesis (HmcFIG 2).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 510, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cd4ae1bc-4ba2-436a-9793-197998278822": {"__data__": {"id_": "cd4ae1bc-4ba2-436a-9793-197998278822", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Head Mesodermal Cell, Section 1) Head Mesodermal Cell](https://www.wormatlas.org/hermaphrodite/muscleheadcell/Mushmcframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "68b27801-8c27-4fb5-b2cf-ec85525e126c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Head Mesodermal Cell, Section 1) Head Mesodermal Cell](https://www.wormatlas.org/hermaphrodite/muscleheadcell/Mushmcframeset.html)"}, "hash": "1b2898595b870a6dd4ed5cb680db70a1c1f0be39b04e8c6eef4e9a5846cc849c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Post-embryonically, the hmc cell body lies dorsomedially to the terminal bulb of the pharynx in the head. It has anteriorly and posteriorly extended processes on both the dorsal and ventral margins of the body wall. A circumferential process from the soma splits at the  pharynx, and these two branches grow along the sides of the terminal bulb of the pharynx, making a loop around the bulb. Ventral to the bulb, these processes first merge and then split to form a ventral anterior arm and a posterior arm. The ventral anterior process runs inside the anterior loop of the right excretory gland process and adjacent to the ventral hypodermal ridge. The ventral posterior arm runs in conjunction with ventral body wall muscle arms and the hypodermal ridge and makes gap junctions with ventral body wall muscle arms (HmcFIG 3) (see also Gap Junctions). The dorsal posterior process runs some distance adjacent to the dorsal hypodermal ridge and makes gap junctions with arms from dorsal muscles. The hmc cell body is flattened and contains a nucleus much like that of body wall muscles except for a smaller nucleolus. In the adult, this cell has very few contractile fibrils, all of which seem to lie within the circular loop of the two ventral processes that wrap around the bulb. These fibrils appear to number too few to perform any significant motor function. Unlike body wall muscles, there are no places at which this cell maintains any obvious anchorage to the cuticle. The extensive gap junctions that the hmc forms with adjacent body wall muscle arms on both the dorsal and ventral sides (White et al., 1976; J.E. Sulston, unpubl.) suggest that this might be useful in synchronizing simultaneous contractions of the dorsal and ventral head and neck muscles. Such a function has been postulated to be important in initiating and coordinating the \u00e2\u0080\u009cflipping\u00e2\u0080\u009d motions of the late embryo, before onset of the larval motor pattern (Hall and Hedgecock, 1991; E. Hedgecock and D.H. Hall, unpubl.).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2001, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0ca59d53-799e-4158-a174-fc03f08ca462": {"__data__": {"id_": "0ca59d53-799e-4158-a174-fc03f08ca462", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Head Mesodermal Cell, Section 1) Head Mesodermal Cell](https://www.wormatlas.org/hermaphrodite/muscleheadcell/Mushmcframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a3745128-1319-4a2e-befc-f9ffc951d6af", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Head Mesodermal Cell, Section 1) Head Mesodermal Cell](https://www.wormatlas.org/hermaphrodite/muscleheadcell/Mushmcframeset.html)"}, "hash": "b0a5b6144bfc4a5eee31c90362e9602225dd96a580d8fa1db4d61c01da000450", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Similar \u00e2\u0080\u009cstomatal\u00e2\u0080\u009d muscles in other nematodes have been postulated to help the digestive function of the grinder, because hmc surrounds the pharynx where the \u00e2\u0080\u009cteeth\u00e2\u0080\u009d are located (Chitwood and Chitwood, 1950). This function seems unlikely in C. elegans due to the inconsequential nature of its contractile motor elements.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 328, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6c1f207f-f4c0-47f8-89f1-3eacdc33dcba": {"__data__": {"id_": "6c1f207f-f4c0-47f8-89f1-3eacdc33dcba", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Head Mesodermal Cell, Section 1) Head Mesodermal Cell](https://www.wormatlas.org/hermaphrodite/muscleheadcell/Mushmcframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "96f96b36-2887-41f7-b004-c58fcd6d64f2", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Head Mesodermal Cell, Section 1) Head Mesodermal Cell](https://www.wormatlas.org/hermaphrodite/muscleheadcell/Mushmcframeset.html)"}, "hash": "f3d078e1968cfae51d0b7319d7da4677abc7359d479afe88d688af88b94f779e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "It is also conceivable that this cell could facilitate the function of the excretory system. The right excretory gland process remains in intimate contact with the hmc for more than 5\u00e2\u0080\u009310 \u00ce\u00bcm and may be a site for electrical coupling, although ultrastructural evidence for gap junctions between the two cells remains ambiguous to date. Because the muscle elements of the hmc are too wispy and the hmc process lies inside the gland process loop, it cannot accomplish any squeezing activity directly on the gland. Nonetheless, perhaps by synchronizing local contraction of all head muscles, this cell could facilitate excretion of granules from the excretory gland or excretion of the liquid contents of the excretory canal sinus.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 729, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cefbd6b6-3971-4f4c-8ab4-94c9a0377af7": {"__data__": {"id_": "cefbd6b6-3971-4f4c-8ab4-94c9a0377af7", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ae489925-d9e8-4da2-b64a-93c16c261d1d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "hash": "6e73d89c3b8fea7d7a06d5790cc0c8479b4d135aca61494e3566a57287a4ffe7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The adult C. elegans hermaphrodite nervous system has 56 support cells that fall into three categories: 24 sheath cells, 26 socket cells, and 6 GLR cells (NeuroTABLE 2). The six GLR cells are located on the inner surface of the NR and are closely associated with the development of the arms of the head muscles. Additionally, unlike neurons and sheath and socket cells, GLRs are mesodermally derived (see Muscle system - GLR cells). The remaining support cells and their related sensory neurons form the sensory organs called sensilla mainly located in the head and tail of the worm.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 583, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "541d36cd-1938-4e52-aaa0-958852017692": {"__data__": {"id_": "541d36cd-1938-4e52-aaa0-958852017692", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 2) Sensillum Structure](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a43a4689-9a42-4844-8804-ac9cd6691122", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 2) Sensillum Structure](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "hash": "c647534cb168bb9b9a3f0befeec30d5ccb1e4ceb51319ca7ceadbf7d434ed4d3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "A sensillum is a simple epithelial sense organ composed of dendrites of one or more bipolar sensory neurons surrounded by a channel formed by a single sheath cell and one or more socket cells (NeuroFIG 22) (Bird and Bird, 1991; Doroquez et al., 2014). At the extreme end of its process, the socket cell forms a small, ring-like tissue that surrounds the distal ends of the cilia of the sensory dendrites, whereas the extreme distal portion of the sheath cell envelops the lumen of the sensillar pouch immediately posterior to  the socket cell. The socket and sheath-cell processes are sealed to each other by electron-dense adherens junctions. Less robust adherens junctions also connect the socket cell to the hypodermis. Virtually all of the sensilla are concentrated in the head and the tail in C. elegans.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 809, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9f71cfac-bb2b-4bc0-a272-f56d3287267c": {"__data__": {"id_": "9f71cfac-bb2b-4bc0-a272-f56d3287267c", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 2.1) Cilium](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2e6e3b35-197c-464d-97ae-efb5b2ab1876", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 2.1) Cilium](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "hash": "6b89f53f3253d2ba7acc644c672ed029d5e1addce4b4e890ee0835e0025948dc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Some sensory neuron dendrites form sensory cilia (nonmotile, microtubule-rich extensions specialized as receptors for diverse sensory modalities) at their termini. Generally, the cilia contain receptor molecules and various signal transduction components. Therefore, it is assumed that they are the primary sites of transduction at which environmental stimuli are converted into receptor potentials.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 399, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1e48a030-b843-416c-bf69-0a5b6f537a1e": {"__data__": {"id_": "1e48a030-b843-416c-bf69-0a5b6f537a1e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 2.1) Cilium](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d880b387-1bc8-4ebe-b641-2db9404bd202", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 2.1) Cilium](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "hash": "5675ca4c5f905b954eff388bbe30ff4b352b2516fb1a764691db3649c82efc88", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The common structure of a cilium in C. elegans is a finger-like process containing nine outer doublet MTs arranged in a circle (9 + 0 axoneme arrangement) around two to six inner, singlet MTs (NeuroFIG 23; NeuroTABLE 3) (Lewis and Hodgkin, 1977; Albert et al., 1981; Perkins et al., 1986). The nine doublet MTs originate from the basal body, which is a modified centriole found at the base of the cilium. The assembly, maintenance, and function of cilia are managed through MT-based intraflagellar transport (IFT), which moves cargo including IFT particles to and from the distal tip. IFT uses canonical, anterograde, heterotrimeric kinesin II and retrograde, cytoplasmic dynein (CHE-3) motors (Barr, 2005; Blacque et al., 2005; Inglis et al., 2007).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 750, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "611664a6-040c-4de4-8729-6767e014afac": {"__data__": {"id_": "611664a6-040c-4de4-8729-6767e014afac", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 2.1) Cilium](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4afea949-a5e9-4a35-82e6-4b9940701005", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 2.1) Cilium](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "hash": "21e592c89bf9857d80ac4c665c61ba800e27dd8ed6de546b77e6c10b7e1a0c0a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In C. elegans, normal cilia development takes place at around the midpoint of the threefold stage of embryogenesis. During ciliogenesis, one of the centrioles converts to a basal body by assembling a transition zone that serves as a docking site for IFT proteins and motors (Li et al., 2004). The basal body serves as a template for the formation of the axoneme, which projects out from the basal body in a bud-like structure covered by the cell membrane. The A and B tubules of the basal body microtubules grow  into the axonemal shaft, generating the nine doublets. Within the transition zone, microtubules are anchored to the cell membrane by transitional fibers that are also believed to be involved in loading IFT motor cargo complexes onto the ciliary axoneme (Blacque et al., 2004; Bossinger and Bachmann, 2004). Precursors are incorporated into the ciliary structures at the distal tip after being carried by IFT motors and IFT particles. Two IFT kinesins, heterotrimeric kinesin-II and OSM-3, work redundantly to build the proximal and middle segments of the axonemes, whereas more distally, OSM-3 alone is required to extend the distal singlets (Ou et al., 2005; Evans et al., 2006). Between 650 and 770 minutes after the first cleavage, the average length of the cilia is 3\u00e2\u0080\u00935 \u00ce\u00bcm (Fujiwara et al., 1999). By 770\u00e2\u0080\u0093800 minutes, cilia have reached an average length of 5\u00e2\u0080\u00937 \u00ce\u00bcm and, by the time of hatching, some of the cilia have grown even longer. Even if normal cilia formation does not take place during embryogenesis, some C. elegans neurons retain the ability to extend cilia in later stages, including the adult stage (Fujiwara et al., 1999).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1661, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2dd6cc43-3f4e-4eaa-a528-f396b700a59f": {"__data__": {"id_": "2dd6cc43-3f4e-4eaa-a528-f396b700a59f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 2.1) Cilium](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "556a44f1-fb3c-4942-b2b7-9dc2dad2ab06", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 2.1) Cilium](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "hash": "fa6926b1d92363ce26658edc4a62ebf39eb56119e4df30ae89b43d35be6948a5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Hermaphrodites have 61 ciliated neurons, and all except three (AQR, PQR, and PVR) are members of bilateral pairs (Ward et al., 1975; White et al., 1986; Hall and Russell, 1991). Twenty six of these 61 neurons have endings that are exposed to the environment and are located in the head amphid and inner labial sensilla and the tail phasmid sensilla. The male possesses an additional 52 ciliated neurons; all except two (HOA and HOB) are also arranged as left\u00e2\u0080\u0093right pairs. In wild-type animals, hydrophobic fluorescent dyes such as fluorescein isothiocyanate (FITC) and the carbocyanine dyes DiO and DiI penetrate into eight classes of ciliated neurons of the amphid and phasmid (Hedgecock et al., 1985; Starich et al., 1995). Mutations that affect cilium structure and hence prevent dye uptake (dye-filling mutant; dyf) have been identified. Tendyf genes were found to affect structure of all neuronal cilia and encode for IFT particle proteins or transcription factors (Perkins et al., 1986; Swoboda et al., 2000; Qin et al., 2001; Sloboda, 2002). Additional dyf mutations are specific to subsets of ciliated neurons and may involve proteins that have a role in refining the structure of specific cilia for certain functions after the general cilium structure has been built (Barr, 2005).\n\n2.2 Socket and Sheath Cells", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1320, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "94c7676d-e1e6-4b58-89e0-9a49fa078a8b": {"__data__": {"id_": "94c7676d-e1e6-4b58-89e0-9a49fa078a8b", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 2.2) Socket and Sheath Cells](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "72714bc1-bf11-4dcb-90d9-1d414c1f119e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 2.2) Socket and Sheath Cells](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "hash": "0267f57514a6f31488d012f80f7eb53b56d250f3868bb0ab16c4f90ef53a4046", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sensillar endings are enclosed within a protected environment by sheath and socket cells, which are specialized interfacial epithelial cells derived from the AB lineage (NeuroFIG 24; NeuroTABLE 2). These are considered to be glial cells, because they are closely associated with the ciliated endings of the sensory receptors of specific sensilla in C. elegans (Ward et al., 1975.) Sheath and socket cells lack synaptic connections or GJs to neighboring neurons, but they are closely related to neurons by lineage  (Sulston et al., 1983). In early development, a hypodermal or seam stem cell such as T and its daughters may have the role of socket in forming a sensory opening before the birth of the true socket cell (Sulston and Horvitz, 1977; Sulston et al., 1983).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 767, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e3667a19-e555-4933-ba00-52b89a67027a": {"__data__": {"id_": "e3667a19-e555-4933-ba00-52b89a67027a", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 2.2) Socket and Sheath Cells](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "815a7be2-843f-4c04-a1f4-7a025ccbaec9", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 2.2) Socket and Sheath Cells](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "hash": "3c2236adda20114e5ba5a510cf51b2b1f8a7f0fce1a53eef5f448a1fb2420a27", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Unlike higher organisms, glia do not form myelin and are not required for neuronal survival in C. elegans. However, they have a role in neuronal development and function, as has been shown through ablation studies (Sulston et al., 1983; Shaham, 2006). Sheath cells regulate dendrite extension, and socket cells are involved in navigating sensory dendrites to specific sensory organs. In the absence of sheath cells, associated sensory dendrites fail to complete their extension, whereas when socket cells are missing, sensory dendrites of that sensillum infiltrate a different sensory organ (Sulston et al., 1983). In addition to regulating dendrite extension and organizing groups of dendrites, glia might also have roles in general axon guidance. During NR development in embryogenesis, inner labial sheaths are suggested to guide axons entering the NR neuropil from the anterior, whereas cephalic sheaths may guide axons entering the ring from the posterior (Wadsworth et al., 1996).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 986, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a8a7e1bc-cedf-43ff-8feb-b35344b55b3f": {"__data__": {"id_": "a8a7e1bc-cedf-43ff-8feb-b35344b55b3f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 2.2) Socket and Sheath Cells](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8bff2dea-f412-4fd3-8d71-bf3cd923ab18", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 2.2) Socket and Sheath Cells](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "hash": "0827453b8aab4508f748b42aff906828d376861739961717f89b410480e928c0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In general, socket cell bodies tend to be smaller and lie closer to the sensilla than the sheath cells (NeuroFIG 22). Each cell extends one long, thin process along the terminal portions of the sheath and neuron processes that wraps around the dendritic tips, distal to the sheath endings. Socket cells are also more epithelial in nature; they connect to the hypodermis via adherens junctions and secrete cuticle that lines the external opening of some of the sensilla. Socket cells make a pore through which sensory dendrites may extend into the cuticle and, in some cases, to the animal\u00e2\u0080\u0099s exterior.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 602, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "16c8f813-0e75-40ae-a268-fef36aaa4402": {"__data__": {"id_": "16c8f813-0e75-40ae-a268-fef36aaa4402", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 2.2) Socket and Sheath Cells](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3af7b4f6-0a5d-448a-9695-186883ad6d74", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 2.2) Socket and Sheath Cells](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "hash": "5fe3a3149e53e890fb375d64c4d09b04f480ea99309da962641cc6a4c4ddbfd7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sheath-cell processes ensheath the ciliary endings of the dendrites proximally to the sockets. Cilia often traverse the sheath-cell cytoplasm in narrow membranous tubes to enter the sensillar channel within the sheath cell. The tubular lumen of the sheath cell comprises the proximal portion of the bipartite sensillar channel, and the hole of the socket ending comprises the distal part. Some sheath cells can be very large, particularly those for the amphids, each of which enclose 12 cilia. Some sheath cells, including the labial and cephalic sheaths, have lamella that project into the lumen of the sensillar channel. Amphid sheaths secrete a granular electron-dense material into the channel that surrounds the cilia (Ward et al., 1975; Bird and Bird, 1991). The sheath cells for smaller sensilla are less complex, but contain some of these features in less dramatic form, often including several small membrane lamellae and a few vesicles near the channel.\n\n 2.3 Accessory Neurons of Head Sensilla", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1004, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7dbebe03-597e-4703-94d6-b2846f63d15b": {"__data__": {"id_": "7dbebe03-597e-4703-94d6-b2846f63d15b", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 2.3) Accessory Neurons of Head Sensilla](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f4f296eb-ae83-48ef-a943-786318b5a969", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 2.3) Accessory Neurons of Head Sensilla](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "hash": "968b705553c1631fd43a64dd7e8141f838779b50c953c4197ce3136641a5394d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Some neurons are closely associated with head sensilla, although they are not truly part of them. All of these are either sensory neurons or suggested to have yet unknown sensory functions. Six of these, two URX and four URY neurons, travel within the labial nerves to the lips, although they do not end within the labial sensilla. URXL/R neurons have unciliated, small bulb-like endings between CEPshDL/R and AmshL/R. URYDL/R neurons terminate in a thin sheet-like structure close to the ILshDL/R and OLQshDL/R, whereas URYVL/R neurons terminate close to ILshVL/R and OLQshVL/R. Similarly, FLP and BAG neurons do not have specific socket and sheath cells assigned to them, although their processes travel within the lateral labial process bundles (see NeuroFIG 19). These ciliated neurons terminate close to the lip cuticle on each side. BAG endings make bag-shaped, swollen structures that wrap short projections from the hypodermis close to IL sensilla at each subventral side (NeuroFIG 25) (Ward et al., 1975; Perkins et al., 1986; White et al., 1986). FLP neurons terminate close to ILsoL/R, but they also send branches to the dorsal and ventral sides (NeuroFIG 10 and NeuroFIG 25) (Ward et al., 1975).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1207, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b9fcc7b1-6801-460e-bf35-b259f136c8dd": {"__data__": {"id_": "b9fcc7b1-6801-460e-bf35-b259f136c8dd", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 3.1) Amphid Sensilla](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "21d27333-faf5-4b32-a729-cb9f2561ad7e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 3.1) Amphid Sensilla](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "hash": "2ea844a0e10467a58ccc3a6ee3546ef60e9af68f1193dcf8be905114a3817f5c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The amphids are a pair of laterally located sensilla in the head that are open to the outside at the sides of the lips. They are the largest chemosensory organs of nematodes. Each amphid includes 12 sensory neurons (ADF, ADL, AFD, ASE, ASG, ASH, ASI, ASJ, ASK, AWA, AWB, AWC) with ciliated dendrites as well as one sheath (Amsh) and one socket (Amso) cell (NeuroFIG 23, NeuroFIG 24, NeuroFIG 25 and NeuroFIG 26, NeuroMOVIE 1). The sensory dendrites of 11 neurons, except those of AFD, completely penetrate the sheath-cell ending through 11 membrane-lined holes in a sieve-like fashion and then enter the sheath pouch (NeuroFIG 24). The cilia of eight of these neurons, except those of AWA, AWB and AWC, extend into the doughnut-like pore created by the socket cell and are exposed to the external medium (NeuroFIG 27). These neurons have roles in chemotaxis, mechanosensation, osmotaxis, and dauer pheromone sensation (NeuroTABLE 1) (Bargmann and Mori, 1997; Driscoll and Kaplan, 1997; Riddle and Albert, 1997; Bargmann, 2006). The cilia of odor-sensing AWA, AWB and AWC neurons invaginate back into the sheath cell and become embedded therein (NeuroFIG 24). The dendrite of the thermosensory AFD is embedded within the sheath cell throughout and terminates in a rudimentary cilium with many villi. The ending of the amphid socket cell does not form a true tube like the sheath cell, but rather, wraps around the distal portion of the cilia-filled channel and seals onto itself with an adherens junction (NeuroFIG 28). The sheath cell is connected to the amphid sensory cilia and the socket cell by adherens junctions, and the socket cell, in turn, is connected to the hypodermis by adherens junctions (NeuroFIG 24).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1716, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "053d482b-3912-46d6-955d-93ac27ce009a": {"__data__": {"id_": "053d482b-3912-46d6-955d-93ac27ce009a", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 3.1) Amphid Sensilla](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d63cf726-ae9b-4937-a400-09b968da36ae", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 3.1) Amphid Sensilla](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "hash": "66593ad0d3a0cd2acca60faab44aca1217bba414299a70442408968044d1751f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Ablation of amphid sheath cells results in behavioral and developmental deficits, including an inability to form dauers in the presence of the pheromone (Bargmann et al., 1990; Vowels and Thomas, 1994). The amphid neurons are then unable to take up FITC in these animals. Sensory function becomes impaired following amphid sheath ablation, even after the sensory organ has formed. Although amphid neurons continue to survive in these animals, their dendritic tips show morphological abnormalities, suggesting a function for the sheath cells in maintenance of amphid ciliary properties (Perens and Shaham, 2005; Shaham, 2005).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 625, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "476c3d5d-4c6a-4d81-9c2c-6091927de1de": {"__data__": {"id_": "476c3d5d-4c6a-4d81-9c2c-6091927de1de", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 3.1) Amphid Sensilla](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bdb873df-87ec-4c15-9cfa-be324db0f182", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 3.1) Amphid Sensilla](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "hash": "60cffbbbc60cf4271c2e3042a6c087f88ae2e8ec8b1fad84e40dad6bdada1cad", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Amphid sheath cells contain large vesicles filled with matrix material that is secreted into the amphid channel (NeuroFIG 24) (Perkins et al., 1986). This electron-dense material, which fills the channel and surrounds the dendritic tips, seems to be important for dendritic structure and function. Defects in matrix production and secretion, as seen in animals with mutations in che-12 (abnormal ), lead to impaired sensory function, poor FITC uptake into the amphid neurons, and shorter channel cilia (Perkins et al., 1986; Starich et al., 1995). Conversely, neurons modulate amphid sheath structure and function. In IFT and cilia formation mutants, matrix secretion from the sheath cells is impaired and a large number of vesicles accumulate within the sheath cells, suggesting that cilia stimulate matrix secretion (Perkins et al., 1986; Collet et al., 1998). In some of these mutants, for example daf-19, amphid channel formation by the sheath cells is also defective and the sheath cells look misshapen.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1008, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9d0ff262-64ef-414e-b857-d32d6360d2a8": {"__data__": {"id_": "9d0ff262-64ef-414e-b857-d32d6360d2a8", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 3.1) Amphid Sensilla](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0abd49a5-5490-4825-b419-4918f24adb01", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 3.1) Amphid Sensilla](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "hash": "e7028b56eefafddf6691e4d891b47dd9b90112a8e3115dce2119c170ca94d816", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Two proteins, DAF-6 and CHE-14, which are involved in the formation of tubular structures, cooperate in building the amphid channel during development (Michaux, 2000; Perens and Shaham, 2005; Shaham, 2006). Amphid channel formation occurs between the comma and 1.5-fold stages (between 330 and 430 min post-fertilization) of embryogenesis (Sulston et al., 1983). As in other epithelial cells, CHE-14 functions in apical sorting and exocytosis within sheath cells, whereas DAF-6 participates in endocytosis. Therefore, these two proteins may regulate sculpting of the apical membrane as the lumen of the sheath channel forms (Shaham, 2006).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 639, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "226fd8d2-b510-4bcf-a2cf-78c751d17af9": {"__data__": {"id_": "226fd8d2-b510-4bcf-a2cf-78c751d17af9", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 3.1) Amphid Sensilla](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "98b2758a-4507-4479-a93a-d8e868e6a0ee", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 3.1) Amphid Sensilla](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "hash": "469639a90900e80d1bbea53f3439d57b83f7dc35b28e3e5cbca05672e15a5138", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "3.2 Cephalic Sensilla", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 21, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a61d5660-e0cb-4196-bdb1-01b85fe4a143": {"__data__": {"id_": "a61d5660-e0cb-4196-bdb1-01b85fe4a143", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 3.2) Cephalic Sensilla](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f1219f90-0564-4f93-9a67-e1ac6d2000d1", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 3.2) Cephalic Sensilla](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "hash": "af630b6a1b149e91eee48c15784d80c9e38850fbc8f1859d27b5f499df22b704", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The CEP sheath cells are the only bipolar glial cells serving two distinct glial functions. Each cell has both an anteriorly directed, dendrite-associated process and a posteriorly directed, lamellar process. The anterior processes travel with those of CEP neurons and CEPso cells to form a channel around the CEP neuron dendrites in the lips (NeuroFIG 30 and NeuroFIG 31). The thin, posterior processes, on the other hand, wrap the outside of the nerve ring and ventral ganglion neuropil, separating these structures from adjacent hypodermis and muscle as well as from some neuron cell bodies (NeuroFIG 32) (Ware et al., 1975; White et al., 1986). Narrow, radial extensions from the sheath cells are also found juxtaposed to a small number of synapses within the NR. It has been suggested that CEPsh cells function in assembly and morphogenesis of the NR during development by providing important substrates for early axon guidance of processes entering the NR from the posterior (Wadsworth et al., 1996).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1006, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4f1ffa3e-2363-4686-b936-77c5bc445f7c": {"__data__": {"id_": "4f1ffa3e-2363-4686-b936-77c5bc445f7c", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 3.3) Inner Labial Sensilla](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c1e77d0d-8e56-4ac9-a333-b0cce122195d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 3.3) Inner Labial Sensilla](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "hash": "190daabbf971ccd6661e33179a700a7289ef93ae1069b71cd152d6752b8fa370", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Inner labial sensilla are found in a sixfold, symmetrically arranged manner at the apex of each lip (ILDL/R, ILLL/R, ILVL/R) (NeuroFIG 33). Each of these sensilla contains two dendrites (IL1 and IL2) as well as one sheath (ILsh) and one socket (ILso) cell (NeuroFIG 34). The IL2 cilia penetrate the cuticle and are exposed to the outside, whereas each IL1 cilium terminates in an electron-dense, membrane-attached disc embedded in the cuticle approximately 0.5 \u00ce\u00bcm below this opening (NeuroFIG 35) (Ward et al., 1975; Perkins et al., 1986). Unlike the amphids, inner labial socket channels are not lined with cuticle; however, an extracellular material surrounds the cilia within the socket and subcuticular channels (Ward et al., 1975). IL and OLQ socket cells express DEG/ENaC sodium channels DELM-1 and DELM-2 which are required cell-autonomously in the socket cells for mechanosensation by IL1 and OLQ, possibly by setting basal neuronal excitability (Han et al., 2013). During development, ILsh cells are suggested to guide axons entering the NR neuropil from the anterior via the six labial nerves (Wadsworth et al., 1996; Antebi et al., 1997). IL1 neurons are mechanosensory and perform head withdrawal in response to dorsal or ventral nose touch (Hart et al., 1995; Kaplan and Driscoll, 1997). From their synaptic interactions, they are also suggested to function as motor neurons and interneurons (White et al., 1986). IL2 neurons are postulated to be chemosensory (Perkins et al., 1986). Only the inner labial sensilla form distinct bumps in the lip cuticle when viewed by scanning electron micrography from the outside (see IntroFIG 4).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1647, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2ccf13ca-aa1d-4128-b6cb-66f118c24ba6": {"__data__": {"id_": "2ccf13ca-aa1d-4128-b6cb-66f118c24ba6", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 3.4) Outer Labial Sensilla](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f551d3eb-fb56-474d-b77c-9e781686fa7e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 3.4) Outer Labial Sensilla](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "hash": "137b3b28fd5d889113d2ad27c4c9056c6450e9675d21b905f76dde1606e91696", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "There are six outer labial sensilla, one on each lip just posterior to the inner labial sensilla (NeuroFIG 36). Each of the outer labial sensilla has only one outer labial sensory neuron dendrite (OLQ or OLL), one sheath (OLsh) cell, and one socket (OLso) cell (NeuroFIG 30) (Ward et al., 1975; Ware et al., 1975; Perkins et al., 1986). Although the fine structures of the OLQ and OLL sensilla differ (NeuroFIG 31), these neurons are placed in the same class on the basis of similarities of positions of their cell bodies, the similarity of their arrangement in the nerve cords, and the location and structure of their sheath cells (Ward et al., 1975). Similar to inner labial sensilla, outer labial sensillar socket channels are not lined with cuticle. The four OLQ neurons are mechanosensory, but they may also function as interneurons (Hart et al., 1995; Kaplan and Driscoll, 1997). Along with IL1 neurons, they transduce signals for head withdrawal response to dorsal and ventral nose touch. Together with ASH and FLP neurons, they also mediate reversal of movement in response to head-on collision. The two OLL neurons are suggested to be mechanosensory (Perkins et al., 1986). IL and OLQ socket cells are involved in mechanosensation by these neurons as noted above.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1272, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "907e8c37-31a1-4476-95d8-d58f0bb5c8da": {"__data__": {"id_": "907e8c37-31a1-4476-95d8-d58f0bb5c8da", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 3.5) Anterior and Posterior Deirid Sensilla](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9943916f-4a31-446e-aca7-e77009eea17c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 3.5) Anterior and Posterior Deirid Sensilla](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "hash": "06c6ce8a8deee131f2c1be2fd6670942a5b4eaad0473c6487ac15ac3cd14f99b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The ADE and PDE neurons are each bilaterally paired, dopaminergic cells. Along with the CEP neurons, they are involved in mechanical texture sensation (NeuroTABLE 1) (Sawin et al., 2000; Hills et al., 2004). Both classes have ciliated sensory endings embedded in the cuticle (Ward et al., 1975; Perkins et al., 1986).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 317, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4e77db6a-0ccf-4f5d-a17a-df27ed1868bc": {"__data__": {"id_": "4e77db6a-0ccf-4f5d-a17a-df27ed1868bc", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 3.5) Anterior and Posterior Deirid Sensilla](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fef602b8-b12a-4e5c-8944-258d3ec263ba", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 3.5) Anterior and Posterior Deirid Sensilla](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "hash": "03fa5066364f81f7a78a4adbeb54556ae441ff51d3b1b8c88aeaba9e663b2994", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Anterior deirid sensilla are located bilaterally at the posterior of the head, positioned within the alae (NeuroFIG 37). An ADE neuron, one sheath cell (ADEsh), and one socket cell (ADEso) comprise the sensillum on each side. ADE neurons lie posteriorly and ventrally to the terminal bulb. The dorsal ADE process sends off a short branch on the side, which extends to the lateral wall and terminates as a cilium (NeuroFIG 38). The dorsal process extends into the ring neuropil and makes synapses with OLL, CEP, and FLP (White et al., 1986). Through the deirid commissures, each ADE ventral process reaches the ventral ganglion neuropil, where it synapses onto RIG and AVA neurons.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 680, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5a36d75f-8c3e-495e-aa7d-80376326081c": {"__data__": {"id_": "5a36d75f-8c3e-495e-aa7d-80376326081c", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 3.5) Anterior and Posterior Deirid Sensilla](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3e4c633b-009e-47cf-8656-34b30b823687", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 3.5) Anterior and Posterior Deirid Sensilla](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "hash": "d96310e67f2affc60669709fc2381321faedba31dc975e585a4aa44a1e7ea997", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Unlike anterior deirid sensilla, posterior deirid sensilla are dorsal to the alae and are located halfway between the vulva and tail, next to dorsal body wall muscle quadrants on each side (NeuroFIG 39). Each posterior deirid sensillum consists of one PDE neuron, one sheath cell (PDEsh), and one socket cell (PDEso) that are born post-embryonically in the L2 stage from the V5 lineage (see Epithelial system). The ventral processes of the PDE neurons extend in a single fascicle with the processes of PVD neurons on each side. They cross the lateral nerves and subventral cords and pass between the hypodermis and ventral body muscles before reaching the VNC (Hedgecock et al., 1990). They bifurcate in the VNC, and both the anterior and posterior branches run in close apposition to their contralateral homologs within the VNC and make GJs to one another. They receive synapses from PVM and PLM and send output onto DVA and AVK neurons (White et al., 1986).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 959, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3991cc9e-6d91-469b-876c-26362a10b683": {"__data__": {"id_": "3991cc9e-6d91-469b-876c-26362a10b683", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 3.6) Phasmid Sensilla](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "81fe39b5-fe35-4ce9-9589-a513abc98289", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 3.6) Phasmid Sensilla](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "hash": "10097a9ca766c3a66139ed5646bd1a00169ce7e22ba5ff7a63f8b5dd71585a65", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The phasmids are located at the lateral sides of the tail, behind the rectum. They are composed of one sheath cell, two socket cells, and  the ciliated dendrites of PHA, PHB, and PQR neurons (only on the left side) (NeuroFIG 40). The phasmids are similar in structure to amphid sensilla, but smaller. The cilia of PHA and PHB neurons extend into the external medium through the hole created by socket cells on both sides, whereas the tip of the PQR dendrite is wrapped within PHso2L (NeuroFIG 41) (Hall, 1977). Cell bodies of the phasmid neurons are located in the lumbar ganglia. Growth of the phasmid neuron axons occurs in two separable stages during embryogenesis; the first stage involves growth into the PAG neuropil through the lumbar commissures pioneered and organized by PVQs and PVT, respectively (Hedgecock et al., 1985). In the second stage, the phasmid axons grow along the posterior VNC and make synapses. No synapses are made within the commissures, and synapses formed in PAG neuropil by lumbar processes, including the phasmid axons, are nearly all dyadic. The PHAs and PHBs form chemical synapses and GJs with their contralateral homologs. Additionally, thePHBs form dyadic synapses onto AVA and PVC interneurons, and PHAs form chemical synapses onto PHB and PVQ neurons (Hall and Russell, 1991). PHA and PHB neurons function in modulation of chemorepulsion behavior in worms, whereas PQR is suggested to be a mechanosensor (Hilliard et al., 2002; Sengupta, 2002).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1483, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7f79a018-2710-492e-bf22-60dbbfb80e4e": {"__data__": {"id_": "7f79a018-2710-492e-bf22-60dbbfb80e4e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 3.6) Phasmid Sensilla](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1a33c9ce-55d3-4ac9-82bd-2f7c9dd6d812", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 3.6) Phasmid Sensilla](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "hash": "85fd623a4eaf06ae7f07706983f68f612f151de36c68a168e552c55ab808bf4d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "At the L1 stage, a seam cell, T, performs phasmid socket cell function and is attached to the sheath cell and syncytial hypodermis by adherens junctions in both sexes. At the L2 stage, when phasmid structure is still indistinguishable between sexes, the T-cell daughters PHso1 and PHso2 perform the socket cell function. PHso1 wraps around the tip of the neuronal dendrites and is connected to PHsh and PHso2, but not to the hypodermis, by adherens junctions. PHso2, on the other hand, is connected to the hypodermis and PHso1, but not to PHsh. Later, male and hermaphrodite phasmids differ in their composition. In the adult male, PHso2 functions as a true socket cell, whereas PHso1 protrudes into the sheath and may contain up to two basal bodies, although it does not display any other characteristics of neurons. In the adult hermaphrodite, on the other hand, PHso1 is the main socket cell and PHso2 has a thin wrapping around it. Phasmid sheath cells extend short processes posteriorly into the tail tip to form a protective channel for PHA and PHB cilia near the phasmid openings.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1087, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a7c5c8bf-4241-48ea-93dd-3714347cb18f": {"__data__": {"id_": "a7c5c8bf-4241-48ea-93dd-3714347cb18f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 4) Other Sensory Neurons of the Tail](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bcaae53d-2708-44b8-a4a7-74b544274377", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 4) Other Sensory Neurons of the Tail](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "hash": "79843fc4cb3e09ab6f507477b8922b344b90ab88276ffa580350d964643bd914", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The tail tip of the hermaphrodite contains other sensory neurons that are not associated with any sheath or socket cells. These neurons are suggested to transduce mechanical signals, for example, during bending of the tail tip (Hall, 1977; Hall and Russell, 1991). Only one of these neurons, PVR, is ciliated. The PVR cilium is buried in the tail tip hypodermis along the postanal ridge. PHCs are bilateral post-embryonic neurons, processes of which do not enter the phasmid sensilla. Long dendritic extensions of the PHC neurons also traverse the tail tip hypodermis, ending finally within a narrow tube of cuticle in the posterior tail whip (NeuroFIG 41). PLN, ALN, and PDB neurons also extend processes into the tail tip that may function as stretch receptors.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 763, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1dcbb0dc-73a1-4e80-b460-14c23c3e1d53": {"__data__": {"id_": "1dcbb0dc-73a1-4e80-b460-14c23c3e1d53", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 5) List of Neuronal Support Cells](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9e21ca31-0334-4f8d-aaf1-50f54cedf018", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 5) List of Neuronal Support Cells](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "hash": "9be0183eea568eaa50b4b9291501d3e36125b50df57c31906c7463fd05a0259c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "1. Sheath Cells ADEshL\n\nADEshR\n\nAMshL\n\nAMshR\n\nCEPshDL\n\nCEPshDR\n\nCEPshVL\n\nCEPshVR\n\nILshDL\n\nILshDR\n\nILshL\n\nILshR\n\nILshVL\n\nILshVR\n\nOLLshL\n\nOLLshR\n\nOLQshDL\n\nOLQshDR\n\nOLQshVL\n\nOLQshVR\n\nPDEshL\n\nPDEshR\n\nPHshL\n\nPHshR", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 208, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4dc7eccb-c9c7-489a-b746-328edc7bd67f": {"__data__": {"id_": "4dc7eccb-c9c7-489a-b746-328edc7bd67f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 5) List of Neuronal Support Cells](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1ca88019-675e-4e15-9b4e-48d0a1e961ab", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 5) List of Neuronal Support Cells](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "hash": "ac519fcf5b0279cc65ec7248f0ff3c78890444aa54316fd62c7bdd262e907ecf", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "2.Socket cells\n\nADEsoL\n\nADEsoR\n\nAMsoL\n\nAMsoR\n\nCEPsoDL\n\nCEPsoDR\n\nCEPsoVL\n\nCEPsoVR\n\nILsoDL\n\nILsoDR\n\nILsoL\n\nILsoR\n\nILsoVL\n\nILsoVR\n\nOLLsoL\n\nOLLsoR\n\nOLQsoDL\n\nOLQsoDR OLQsoVL\n\nOLQsoVR\n\nPDEsoL\n\nPDEsoR\n\nPHso1L\n\nPHso2L\n\nPHso1R\n\nPHso2R\n\nTL (postembryonic blast cell; functions as phasmid socket in L1)- see Epithelial System-Seam Cells\n\nTR (postembryonic blast cell; functions as phasmid socket in L1)- see Epithelial System-Seam Cells", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 425, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f106d487-5690-465f-a30a-5a79f99ef1bb": {"__data__": {"id_": "f106d487-5690-465f-a30a-5a79f99ef1bb", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 6) References](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ba1509af-7c6b-4c31-83db-1b6ce4ba93e6", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Neuronal Support Cells, Section 6) References](https://www.wormatlas.org/hermaphrodite/neuronalsupport/Neurosupportframeset.html)"}, "hash": "a8a07ec5fbc6ca8cf6c0963493eb3ffabaa794860a6e550f7c44f315cdd5182f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sulston, J., Dew, M. and Brenner, S. 1975. Dopaminergic neurons in the nematode Caenorhabditis elegans. J. Comp. Neurol. 163: 215\u00e2\u0080\u0093226. Abstract", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 145, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6390f491-75cc-418b-8e45-2fa7263c3489": {"__data__": {"id_": "6390f491-75cc-418b-8e45-2fa7263c3489", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Rectum and Anus, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/rectum/Rectframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "011050ee-61c9-4d64-adfc-d2e10a92db33", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Rectum and Anus, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/rectum/Rectframeset.html)"}, "hash": "c4afb81027c5eed53ff99129d004293967dbea703fbc06a219078d37d77d09ae", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The hindgut includes the posterior intestine and the passageway between the intestine and the exterior. This passageway contains a valve (vir) between the intestine and the rectum (vir), the rectal gland, the rectum itself and a wide cuticle-lined passage to outside called the anus (RectFIG 1). A total of 11 cells of three distinct types sequentially arrange into these structures creating the passage (IntFIG 2) (Sulston et al., 1983; Sewell et al., 2003). Contrary to the monoclonal origin of the intestinal cells, the cells of the hindgut originate from assorted AB and P1 lineages during development. Several specialized muscles are also associated with the hindgut (RectFIG 1).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 684, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ee97ca13-e110-444f-8bd9-621bacc32d9f": {"__data__": {"id_": "ee97ca13-e110-444f-8bd9-621bacc32d9f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Rectum and Anus, Section 2) Rectal Valve](https://www.wormatlas.org/hermaphrodite/rectum/Rectframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "87829b99-2b3f-4211-aa97-42b2853ce199", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Rectum and Anus, Section 2) Rectal Valve](https://www.wormatlas.org/hermaphrodite/rectum/Rectframeset.html)"}, "hash": "ad00294cfa2e420af70268a95e651f5217b279dbea6a1b9f15e945e2d0a7e29e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The intestinal-rectal valve is formed by two small darkly staining epithelial cells, virL and virR, that occlude the lumen of the posterior intestine (IntFIG 2 and RectFIG 2). Very narrow channels perforate this occlusion to allow digested material to leak into the rectum and then to the anus. It is not apparent whether these small openings are flexible enough to constitute a true valve, because rectal valve cells themselves do not possess any contractile elements or any movable parts.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 490, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e215b9af-069c-4d5d-a14b-56eecd69ab74": {"__data__": {"id_": "e215b9af-069c-4d5d-a14b-56eecd69ab74", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Rectum and Anus, Section 2) Rectal Valve](https://www.wormatlas.org/hermaphrodite/rectum/Rectframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7a4f5ff9-c6aa-4928-88cf-af8274c6f144", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Rectum and Anus, Section 2) Rectal Valve](https://www.wormatlas.org/hermaphrodite/rectum/Rectframeset.html)"}, "hash": "dc1ac1a91e11ba819c385ecd8cd586ec8653b07e6ca7250eef90468a78a9fcd8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The valve cells are sister cells derived from the ABprpapppp cell. Through ablation studies it has been shown that ABplpapppp also has the potential to produce valve cells during development. However, in the wild type animal, ABprpapppp is specified for this function. Normally, ABplpapppp gives rise to the rectal epithelial D cell and PVT neuron when the descendants of ABprpa and ABplpa contact each other at the midline after gastrulation. If this cell-cell interaction is blocked, such as in animals with gastrulation defects, both cells then give rise to valve cells (Bowerman et al., 1992; Bucher and Seydoux, 1994).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 623, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8efac9ee-d81f-41c1-aac6-9cdf06d3be1d": {"__data__": {"id_": "8efac9ee-d81f-41c1-aac6-9cdf06d3be1d", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Rectum and Anus, Section 3) Rectal Gland](https://www.wormatlas.org/hermaphrodite/rectum/Rectframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7bdc7ba7-17bd-41ba-8f7d-b1a255f934e8", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Rectum and Anus, Section 3) Rectal Gland](https://www.wormatlas.org/hermaphrodite/rectum/Rectframeset.html)"}, "hash": "7f9b7cfb93f830afb7e5b958e62421191299c6ea7cb2fe84f9cc6c2289596419", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "A ring of three large rectal gland cells - rect_D, rect_VL, rect_VR (in some older literature, these cells are also referred to as \u0093rep\u0094) - connect to the intestinal lumen just posterior to the rectal valve (RectFIG 2). It is possible that these cells secrete digestive enzymes into the caudal lumen of the intestine, which is slightly inflated compared to lumen in the midbody. The cells lie at the same level or just behind the rectal valve, and their apical specialization facing the lumen produces both microvilli (similar to intestinal cells) and cuticle (similar to transitional epithelia) in discrete patches (D.H. Hall, unpubl.).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 637, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b6978504-bdc3-4a49-aadc-f30175e0e1f4": {"__data__": {"id_": "b6978504-bdc3-4a49-aadc-f30175e0e1f4", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Rectum and Anus, Section 4) Rectal Epithelium](https://www.wormatlas.org/hermaphrodite/rectum/Rectframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "15895761-3cfd-4a34-a86e-68c674ca7310", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Rectum and Anus, Section 4) Rectal Epithelium](https://www.wormatlas.org/hermaphrodite/rectum/Rectframeset.html)"}, "hash": "c1205d59bd958c1b816b4f56226f64efd8a922d9f9d6b8a101a5ede143a0d000", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The Pax transcription factor EGL-38 has been found to be important for the development of hindgut cell types. Downstream of EGL-38, a combination of transcription factors contribute to each cell\u0092s fate (Chamberlin et al., 1997; Sewell et al., 2003)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 248, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "47ace1a7-5323-41cd-83a8-5365769c0404": {"__data__": {"id_": "47ace1a7-5323-41cd-83a8-5365769c0404", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Rectum and Anus, Section 5) Muscle Cells of the Hindgut (Enteric Muscles)](https://www.wormatlas.org/hermaphrodite/rectum/Rectframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7e4e6e9e-a6b4-491f-9468-5ef6df592851", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Rectum and Anus, Section 5) Muscle Cells of the Hindgut (Enteric Muscles)](https://www.wormatlas.org/hermaphrodite/rectum/Rectframeset.html)"}, "hash": "b3bce3d75d47eb6e592563567b64f97ef9510c53acb529d1d2b5e13488687a0d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The four specialized muscle cells of the hindgut (the two stomatointestinal muscles [also called the intestinal muscles], the anal sphincter muscle [also known as the anal dilator or rectal muscle], and the anal depressor muscle [also called the depressor ani muscle]), are reviewed in detail in the Muscle System - Nonstriated. These enteric muscles operate jointly in the defecation cycle. The sphincter and anal depressor muscles are anchored to the body wall and to the rectal epithelium (RectFIG 3). All four muscles send arms to the DVB neuron along dorsal surface of the preanal ganglion. The DVB neuron makes synapses onto the arms of stomatointestinal muscle and the anal depressor muscle. All three sets of muscles are coupled to each other via gap junctions (White et al., 1986) (see also Gap Junctions). Their coupled contractions control the enteric muscle contraction (EMC) step of defecation.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 907, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7f8db6f6-dc00-498d-b513-787bee3df33e": {"__data__": {"id_": "7f8db6f6-dc00-498d-b513-787bee3df33e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Rectum and Anus, Section 6) Motor Neurons of Defecation](https://www.wormatlas.org/hermaphrodite/rectum/Rectframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6a16c38b-7046-4029-9ab8-8d6e718fc035", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Rectum and Anus, Section 6) Motor Neurons of Defecation](https://www.wormatlas.org/hermaphrodite/rectum/Rectframeset.html)"}, "hash": "9573633acc8606b89e61ce2104a66ee3c1f76c9c4f5e6e9b3750bdc4bc20bdea", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In C. elegans, defecation is achieved through rhythmic activation of a stereotyped cycle of muscle contractions (Liu and Thomas, 1994). Laser ablation of the AVL and DVB neurons together eliminate enteric muscle contractions. AVL is an excitatory \u03b3-aminobutyric acid (GABA)ergic interneuron/motorneuron that is located in the head and sends a process  to the tail. It influences the enteric muscles indirectly via gap junctions with DVB (see also Gap Junctions). Killing AVL alone causes a strong anterior body muscle contraction (aBoc)-defective defecation phenotype. Because this defect is not seen in mutants that lack GABA, AVL may also use a non-GABAergic signal to activate other motor neurons that control anterior body wall muscle contraction. DVB is a GABAergic motor neuron located in the dorsorectal ganglion in tail (NeuroFIG 18). It is born post-embryonically at late L1 stage and is the daughter of the K rectal epithelial cell. DVB extends a prominent process anteriorly that passes through a commissure beneath the depressor muscle and extends forward along the top of the ventral hypodermal ridge. In this region, its large axon is filled with synaptic vesicles and makes periodic synapses to muscle arms from enteric muscles. The excitatory GABAergic signal from AVL and DVB is thought to be mediated by the nonselective cation-channel-type GABA receptor EXP-1 because exp-1 mutants lack enteric muscle contractions and are phenotypically constipated (Thomas, 1990; Beg and Jorgensen, 2003).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1509, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c00674b2-37ba-49d1-a6eb-9bb0ab64784d": {"__data__": {"id_": "c00674b2-37ba-49d1-a6eb-9bb0ab64784d", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Rectum and Anus, Section 7) Defecation Motor Program](https://www.wormatlas.org/hermaphrodite/rectum/Rectframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "496f00d4-04fb-401e-9df6-71c41b118c5b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Rectum and Anus, Section 7) Defecation Motor Program](https://www.wormatlas.org/hermaphrodite/rectum/Rectframeset.html)"}, "hash": "61181c66d7be3d02ec35744359403f5fb7f83bf14d6e87d04c80909ac5bf6bfb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In C. elegans, defecation consistently occurs approximately every 50 seconds and has five cycle components: an intercycle period, pBoc (posterior body muscle contraction), pBoc relaxation, aBoc and EMC (enteric muscle contraction) which is also called the expulsion (exp) step (Avery and Thomas, 1997). In the hermaphrodite, each defecation starts with pBoc, which squeezes intestinal contents anteriorly. Approximately 1 second later, relaxation occurs and intestinal contents flow posteriorly. Next, aBoc is initiated by contraction of the body muscles near the head, and gut contents are concentrated near the anus. Finally, contraction of the enteric muscles expels the gut contents out of the animal and the intercycle period starts. The motor components of defecation behavior (pBoc, aBoc and EMC) constitute the defecation motor program (DMP). Defects in any of the motor components of DMP lead to constipation. During larval stages the hindgut structures of the male are virtually identical to those of the hermaphrodite. In the adult male although DMP is similar to the hermaphrodite, the anatomy and control of the hindgut changes drastically (see Male - Defecation Muscles, Male Muscles - Overview).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1210, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "529d6bb1-428a-457f-8fab-2e2cfdfb76fe": {"__data__": {"id_": "529d6bb1-428a-457f-8fab-2e2cfdfb76fe", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Rectum and Anus, Section 7) Defecation Motor Program](https://www.wormatlas.org/hermaphrodite/rectum/Rectframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "01496e18-cf7e-4910-ad3f-b2d102932f58", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Rectum and Anus, Section 7) Defecation Motor Program](https://www.wormatlas.org/hermaphrodite/rectum/Rectframeset.html)"}, "hash": "24e10d9f4e7148cf4a18c83cf91ca58d6ce0f267b66a023d641a700a416fb6ba", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The steps of the DMP are coordinated in precise temporal and spatial sequences. The ultradian defecation rhythm can be reset by light touch stimulus to the body and is thought to be controlled by an intestinal pacemaker that keeps time and activates the posterior body contraction at the start of each cycle (Dal Santo et al., 1999; Siklos et al., 2000). An essential element of this pattern generator and time keeper is the periodic, autonomous calcium release mediated by the inositol trisphosphate (IP3) receptor ITR-1 in the posterior intestine (Dal Santo et al., 1999). Intestinal calcium levels oscillate with the same periodicity as the defecation cycle and reach their peak levels just prior to the first muscle contraction (pBoc) step. Transient increases in calcium ions then propagate from the posterior to the anterior intestine (Espelt et al., 2005; Teramoto and Iwasaki, 2006). Blocking propagation of this calcium wave stops the later phases of the defecation motor program.\u00a0 In addition, mutations in itr-1 slow down or eliminate the cycle, further supporting the idea that IP3 receptor activity and calcium release rather than neuronal control sets the defecation cycle frequency. Nevertheless, the GABAergic motor neurons, AVL and DVB are required for the execution of the anterior body contraction and the enteric muscle contractions for expulsion (McIntire et al., 1993; Avery and Thomas, 1997). An intercellular signal originating from the calcium oscillations in the posterior intestine may activate these two neurons for later muscle contractions.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1570, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6afba1ea-39d8-4ac6-aabd-73a9c7ec68bb": {"__data__": {"id_": "6afba1ea-39d8-4ac6-aabd-73a9c7ec68bb", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "990923bd-e4fe-4dde-a7c0-b6104c16b473", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "c1cc6cc817bd5716f1ca277c19eb20c8e5e012248b66b72b14c27c0b80314d20", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "C. elegans feeds on bacteria in liquid suspension. Bacteria taken in by the mouth are concentrated, ground and transported to the intestine by a tube-like muscular pump called the pharynx. The pharynx is an epithelial organ that has its own muscles, nervous system, gland cells and structural cells. It contains 9 epithelial cells, 20 muscle cells, 9 marginal cells, 4 gland cells and 20 neurons (PhaFIG 1), and 6 valve cells at its posterior (see also PharynxAtlas). It is about 100 \u00b5m long and has a diameter of approximately 20 \u00b5m at its widest (at the posterior bulb). At the anterior, it is connected to the buccal cavity and at the posterior, to the intestine. The pharynx is isolated from the rest of the animal by a specialized basal lamina that lines the basal surface of the pharyngeal cells and isolates the pharynx from the pseudocoelom. There may be hormonal signaling between this organ and the rest of the body by way of the pseudocoelomic fluid. The apical surface of the pharyngeal cells lies medially towards the lumen, which is lined with a cuticle secreted by the pharyngeal muscle and marginal cells. At several locations pharyngeal cuticle takes the form of specialized structures, such as the anterior \u0093flaps\u0094, the \u0093sieve\u0094 and the \u0093grinder\u0094 (PhaFIG 2; see Cuticle) (Avery and and Thomas, 1997).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1317, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9bd91399-5aaa-4f0d-9ede-28d3e50f606b": {"__data__": {"id_": "9bd91399-5aaa-4f0d-9ede-28d3e50f606b", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "88bd6582-a4f6-43fe-a80c-e41dab6ce3d7", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "d351316f1d6112207534f8c167682700f2129de0ec6d4408eb9a346776a9d7de", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The pharynx has a distinctive shape; an extended anterior portion (procorpus) is connected to the buccal cavity via the pharyngeal epithelium (Albertson and Thomson, 1976; Franks et al., 2006). The metacorpus, also called the first bulb, lies posterior to the procorpus. The procorpus and metacorpus together make the corpus of the pharynx. Between the corpus and the second bulb (also called the terminal bulb) lies the isthmus (PhaFIG 2). The large somatic nerve ring surrounds the isthmus on the outside.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 507, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d00cebc6-cfca-4601-893f-ce8f353e35e9": {"__data__": {"id_": "d00cebc6-cfca-4601-893f-ce8f353e35e9", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1ad345cf-939e-487d-9c78-9dcec0badde3", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "bc9cfed2fe7cda7d011403685d8562e4f9e03d42e8ab1a91ea74471985518970", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The pharynx has intrinsic myogenic activity that is regulated by its nervous system. When the entire pharyngeal nervous system is ablated, the pharynx continues to pump, albeit in a slow and uncoordinated manner (Avery and Horvitz, 1989). The nervous system, in turn, integrates internal signals such as the animal\u0092s nutritional status and external signals such as the presence or absence of food (Avery and Horvitz, 1989; Franks et al., 2006). In the absence of food, the pharynx pumps approximately once every second, whereas in the presence of food the rate increases to about four pumps per second. Starved and well-fed worms show initially different pumping rates upon transfer from solid to liquid media (Avery et al., 1993; McCloskey et al., 2017). The pumping rate of the pharynx is also modulated by the somatic sensory system; for example, pumping is briefly inhibited upon sensing a light touch to the body (Chalfie et al., 1985; Avery and Thomas., 1997).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 966, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7cd80676-8f3b-44a4-a143-0a40e6e7e2e4": {"__data__": {"id_": "7cd80676-8f3b-44a4-a143-0a40e6e7e2e4", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 2) Embryonic Development of the Pharynx](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e43175eb-e493-4728-bec9-ef72c5587bea", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 2) Embryonic Development of the Pharynx](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "86a0e7f4277f2f86bae14a84cde2b2f979c49eaa562c3dda63ca4935d9d2354c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Unlike the intestinal cells, all of which arise from a single founder cell E, the pharynx is composed of cells that arise from both AB and MS founder cells (AlimFIG 1). In these lineages, no strict clonal and lineal derivation can be recognized, and there is a heterogeneity of ancestry with respect to the final cell fate (PhaMOVIE 1&2). In the anterior divisions, no lineal boundaries exist between hypodermal, arcade and pharyngeal daughters. The pharyngeal components derived from MS and AB do not possess any functional boundaries either, such that in pm3, pm4 and pm5 muscle groups identical cells arise from these two lineages and some MS descendants fuse with those coming from the AB blast cell (Sulston et al., 1983; Horner et al., 1998).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 748, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "44bda47d-6fc3-41ad-8a70-6f42d617cea1": {"__data__": {"id_": "44bda47d-6fc3-41ad-8a70-6f42d617cea1", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 2) Embryonic Development of the Pharynx](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "34361912-f175-4ced-86f9-bf935579199a", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 2) Embryonic Development of the Pharynx](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "f306427dc69e3901b77060dcaef34a103a5755475d681831eeb2795834735be3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "During gastrulation, at approximately the 100-cell stage and after the movement of gut precursors to inside of the embryo, MS descendants start to move inward through the blastopore (AlimFIG 1 and PhaFIG 3A-D) (Bucher and Seydoux, 1994; Mango, 2007). Slightly later, AB-derived precursors of the pharynx move inside of the embryo. At 150-260 minutes, pharyngeal precursor cells arrange in a bilateral \u0093double plate\u0094 organization (Rasmussen et al., 2013). This is followed at 330-390 minutes by nuclear movement and constriction of cell\u0092s apical boundaries at the double plate midline leading to the formation of a compact \u0093cyst\u0094 pharyngeal primordium (Rasmussen et al., 2008; Rasmussen et al., 2013). These cells are attached to each other and to the midgut by adherens junctions. However, they are not yet attached to the buccal cavity (see Epithelial System - Hypodermis) (Portereiko and Mango, 2001). At this time, 78 of the 80 pharyngeal cells are already born. During the next hour, pharyngeal extension occurs such that the pharyngeal precursors reposition themselves to form a central cylinder and link to the buccal cavity, whereas the body myoblasts position themselves between this cylinder and the outer layer of cells. Pharyngeal extension is accomplished in roughly three steps: reorientation, epithelization and contraction (see Epithelial System - Hypodermis) (Portereiko and Mango, 2001). Later, the pharyngeal tube morphs into a bilobed structure and develops a lumen. Lumen formation is thought to be performed by retraction of the tips of the marginal cells from the midline of the pharyngeal primordium when the pharyngeal muscles differentiate and contract (PhaFIG 3E-G) (Leung et al., 1999). An exception to this is the pm8 and vpi1 cells at the posterior end of the pharynx, which form adjacent single cell tubes through detachment from the basal lamina, lamellar invasion, and self-fusion. vpi1 forms a toroidal tube during embryogenesis that connects with itself through self-fusion (Rasmussen et al., 2008). Cell fusions in the pharynx occur either before or soon after hatching (Sulston et al., 1983). C. elegans initiates pharyngeal pumping right before hatching.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2191, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "36f1fc61-dc61-4607-b0e9-32a3d23ba55e": {"__data__": {"id_": "36f1fc61-dc61-4607-b0e9-32a3d23ba55e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 3) Pharyngeal (Buccal) Epithelium](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6a44ba03-8919-4d7c-89a2-178ac22d7d04", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 3) Pharyngeal (Buccal) Epithelium](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "8931e6be636d6483f05508f692155eb82f51502ebf8c9edc89da4281c06d4f79", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "A series of interfacial cells join the lips to the buccal cavity and the buccal cavity to the pharynx (See Epithelial System - Interfacial Epithelial Cells; PhaFIG 4A-D; PharynxAtlas) (Wright and Thomson, 1981). The buccal cavity is surrounded, from anterior to the posterior, by the anterior hypodermis and the arcade cells, which constitute the anterior limit of the pharyngeal lumen (PhaFIG 4E-I; InterFIG 1; InterFIG 3). Each of these cells contributes small territories along the buccal cavity and their cell bodies lie more posteriorly in the head. The arcade cells are contiguous with the pharyngeal epithelium, a thin tube made from nine cells, formed by two successive rings of nonsyncytial tissue with sixfold symmetry (PhaFIG 5) (Albertson and Thomson, 1976). Similar to the anterior hypodermal cells and the arcade cells, the cell bodies of the epithelial cells lie far posterior to the buccal cavity and extend thin processes anteriorly within the pharyngeal nerve cords to reach their territories surrounding the lumen (Albertson and Thomson, 1976). The most anterior epithelial cells, e1, are positioned as a single dorsal and two subventral cells, covering markedly thinner territories (as measured along the a/p axis) than the other six cells. The posteriormost cells, e3, are positioned in the same pattern, and their epithelial territories lie directly behind those of e1 cells. The intervening e2 cells lie at the three apices of the triangular lumen, and their epithelial territories span the width of both the e1 and e3 cells, yielding a sixfold symmetry. At their lateral borders, all of these epithelial cells are firmly connected to their immediate neighbors by large adherens junctions (running continuously at the apical border). Where the epithelial cells border the posterior arcade cells, there are again very prominent adherens junctions (PhaFIG5 D&E).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1883, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "61f4e696-cdbe-4a3f-b501-39488f6fae49": {"__data__": {"id_": "61f4e696-cdbe-4a3f-b501-39488f6fae49", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 3) Pharyngeal (Buccal) Epithelium](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "678b5cc2-2a5f-45c4-8c2a-342c77aea82a", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 3) Pharyngeal (Buccal) Epithelium](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "655fc9c9e35dabf2174568f8f6c25d4775d68af33a33b88add93d740bafc1df6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The pharyngeal epithelium is a rather rigid narrow cylinder that restricts entry of food into the pharynx. Its cylindrical shape is heavily reinforced by short radial bundles of intermediate filaments anchored to the apical and basal membranes of the epithelial cells by large hemidesmosomes. These well-anchored filaments seem to limit the epithelial cylinder from stretching or collapsing, despite the vigorous movements of the nearby pharyngeal musculature. The pharyngeal epithelial cells also secrete the cuticle that lines the buccal cavity along the former mesostom portion.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 581, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a6498b01-12b9-4520-9763-196628147d6c": {"__data__": {"id_": "a6498b01-12b9-4520-9763-196628147d6c", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 3) Pharyngeal (Buccal) Epithelium](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "40592990-698f-4fc0-abda-63ddc503eafe", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 3) Pharyngeal (Buccal) Epithelium](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "52477ce898a3888278d29247c25058eb08c0f6700d1803ba6b4a81f30b7db8a1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The inside caliber of the buccal epithelial lumen increases markedly at each larval molt, and this increase in size of the buccal cavity is suggested to permit increased growth rate after each molt (Knight et al., 2002). The buccal cavity is much narrower in the dauer larva, which stops actively feeding (DCutFIG4).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 316, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5b7943ae-440d-4683-8721-70cc2d998010": {"__data__": {"id_": "5b7943ae-440d-4683-8721-70cc2d998010", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 4) Muscle Cells of the Pharynx](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "30f604b3-4ba0-4f5e-a633-99204c97d32d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 4) Muscle Cells of the Pharynx](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "473420db4b194cd5e4959df99e0fe21e71900a55157c9f40f6e76f45f339b5a1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The pharyngeal muscles are grouped into eight separate segments (pm1-pm8), which are arranged as eight consecutive rings encircling the pharynx (PhaFIG 6A-C; PharynxAtlas) (Albertson and Thomson 1976; Avery and Thomas, 1997; Franks et al., 2006). Unlike the body wall muscles, no hypodermal layer separates the muscle anchorage from the cuticle lining the lumen of the pharynx. Indeed, most of the pharyngeal muscles appear to participate directly in secreting cuticle (e.g., the two anteriormost pharyngeal muscle cells, pm1 and pm2, secrete the cuticle that lines the metostom and telostom portions of the buccal cavity) and thus qualify as having myoepithelial properties (Albertson and Thomson 1976, D.H. Hall, unpublished). Consistent with this, the pm1 cells are required for secretion of the metastomal flaps (Sando et al., 2021). Most of the pharyngeal muscle segments are made up of three syncytial cells positioned in a three-fold symmetrical manner in any cross section (PhaFIG 6D). Each of these cells contains two nuclei as a result of fusion of two cells around the time of hatching (See Table 1 in Albertson and Thomson 1976; see also PhaTABLE 1). In pm2-pm5 of adult pharynx, there are still small remnant adherens junctions at the sites of former cell fusions between pairs of muscle cells, marking the exact apical border where the fusion has occurred (PhaFIG 3) (Hedgecock and Thomson, 1982). These remnant junctions express the AJM-1 protein and can be stained by immunocytochemistry (Koppen et al., 2001; D.H. Hall, unpublished). The three muscle cells of each segment are separated from each other by three marginal cells, whereas the muscle cells of the neighboring rings are linked by gap junctions and also connected via interlocking short fingers on the anterior and posterior margins. Each syncytial muscle cell contains a deep groove on the basal side where a longitudinal pharyngeal \"nerve cord\" is situated (PhaFIG 6 and PhaFIG 7A). These nerve cords enclose the cell bodies and processes of neurons, gland cells, and anterior epithelial cells. Many synapses, including neuromuscular junctions onto the pharyngeal muscles, occur along these cords.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2177, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b6785653-42d0-4e28-8c44-fe74908719d1": {"__data__": {"id_": "b6785653-42d0-4e28-8c44-fe74908719d1", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 4) Muscle Cells of the Pharynx](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b25faa16-d3a2-44af-9bd9-2397cf76fe7d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 4) Muscle Cells of the Pharynx](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "8447e74be0f18c4240fdb8dd2bcec193fa6bc60a9fa849ab8a7f23af3a1ac28d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Specialized zones mark the apical regions of several of the pharyngeal muscles where they secrete cuticle. Here, the cytoplasm contains electron dense tubules, and sometimes, dense core vesicles just under the plasma membrane. The cytoplasm of pm6 is particularly specialized in the region underlying the grinder, which is a very elaborate cuticular structure secreted by the pm6 muscle cells (PhaFIG 2). During the lethargus period preceding each larval molt, pm6 and pm7 produce secretory vesicles, which interrupt the sarcomeres. Vesicles with electron dense cores predominate during shedding of the L4 cuticle, while electron lucent core vesicles are dominant during the formation of the adult cuticle (Sparacio et al., 2020). Prominent networks of sarcoplasmic reticulum along the borders of each muscle sarcomere presumably sequester calcium needed for muscle contractility. Pharyngeal muscle cells also contain many mitochondria.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 936, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b8423617-6be7-4b72-ab98-88c8b45aeb9b": {"__data__": {"id_": "b8423617-6be7-4b72-ab98-88c8b45aeb9b", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 4) Muscle Cells of the Pharynx](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a3b82e53-212d-4166-b655-cc1c838e3b6e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 4) Muscle Cells of the Pharynx](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "0e6f1c5f31619d854f4b519b95d96b29dc82fb0935c5e8cde2b24c98d170bdd0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In most pharyngeal muscle segments, contractile filaments are oriented radially, and when the muscles contract, the pharyngeal lumen opens. However, in the terminal bulb, the pm7 muscle filaments are oriented obliquely with regard to the anterior-posterior axis and pull on the grinder region when the muscle contracts. pm1-pm4 function in sucking up and trapping bacteria. pm5 regulates flow of food from corpus to the terminal bulb, and pm6-pm8 operate the grinder.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 467, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "74034551-df58-4460-9174-c27997e9a417": {"__data__": {"id_": "74034551-df58-4460-9174-c27997e9a417", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 5) Marginal Cells](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d89e2535-133a-4aeb-983f-f18a6ce0b5df", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 5) Marginal Cells](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "6682409fa8561bbf498c87bd3ed92f42e5cd8a9bf917ccd8dd242f9e8a607187", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The pharynx is a mosaic of several non-equivalent cell types, each with threefold symmetry that assemble into a nonstratified, one-cell-deep epithelium along the lumen (PhaFIG 7A; PharynxAtlas). As described above, muscle cells are a major part of this epithelium. Cells of another type, the marginal cells (mc), are placed at the three corners of the pharyngeal lumen and separate the muscle cells from one another. There are three mc segments along the pharynx and a total of seven marginal cells; three mc1 cells comprise the anterior segment, three mc2 cells comprise the second segment, and a syncytial mc3 cell with three nuclei comprises the terminal bulb segment (PhaFIG 1 and PhaFIG 6). From segment to segment, the marginal cells lie in rows at the corners of the lumen. They vary markedly in size between segments, but the three cells within one segment are essentially equivalent.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 892, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6886e95d-b930-4ae2-aa64-c4b5d0f3926f": {"__data__": {"id_": "6886e95d-b930-4ae2-aa64-c4b5d0f3926f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 5) Marginal Cells](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7ecd7463-bb3e-4f0f-8d6a-71fa13a69dae", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 5) Marginal Cells](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "f73b1d5ea187b603510fd658326b60fa8000b36d8e71f8982868225953cc0281", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Marginal cells supply reinforcing strength to this muscular organ. Their large size and block-like shape is fortified by the placement of large radial bundles of intermediate filaments running from apical to basal borders of each cell. These filaments are anchored to the plasma membrane by large hemidesmosomes. Within each segment, the marginal cells are linked to neighboring muscle cells on their lateral borders by large gap junctions as well as apical adherens junctions separating the membrane to apical and basal surfaces (PhaFIG 7B&C) (Avery and Thomas, 1997). Large interlocking finger-like extensions also connect marginal cells to muscles within each segment and may also add to the structural integrity of the whole organ. Because of this arrangement, marginal cells within a segment communicate with muscle cells of the same segment and not with other marginal cells. In contrast, between segments, these cells form interlocking fingers and gap junctions to neighboring marginal cells.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 999, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9fa3a5c3-ecba-45f3-8695-41ed8c5d8c6a": {"__data__": {"id_": "9fa3a5c3-ecba-45f3-8695-41ed8c5d8c6a", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 5) Marginal Cells](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "25b77a31-cac5-439f-8b34-de7bbac86684", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 5) Marginal Cells](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "7265a68f67b289de28b51abca203db97857ff206bae971fab169632a7485c0bb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The marginal cells contain many mitochondria, which suggests that these cells may perform some active role beyond merely providing continuity and strength to the epithelium. Because marginal cells are coupled to pharyngeal muscles via gap junctions, they may have some motor function, i.e., they may be myoepithelial in nature. Alternatively, they may act as relay stations to synchronously transmit signals from motor neurons to surrounding pharyngeal muscles so that all pharyngeal muscles within a segment can contract and relax at the same time. It is noteworthy that when the pharyngeal muscles contract, the muscle cells become thinner to open the lumen. Because the marginal  cells are already relatively thin, this suggests that at full contraction, the pharyngeal lumen may open practically as wide as the inside corners of the marginal cells and form an open triangular lumen, whereas when the muscles relax, the lumen is practically closed except for the three channels at the apices of the anterior lumen.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1017, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "738461fa-0e63-4c67-bb06-88b4334268d9": {"__data__": {"id_": "738461fa-0e63-4c67-bb06-88b4334268d9", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 6) Gland Cells of the Pharynx](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8eeb862b-caf8-4094-842f-8a3788adf8b1", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 6) Gland Cells of the Pharynx](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "7660dabffb136db25c5cfcdcea581ce2baf424dfd27f7db74c56fb1af82195cb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Two classes of gland cells, g1 (three cells) and g2 (two cells), are found in the second bulb of the pharynx (PhaFIG 8; PhaMOVIE 3; PharynxAtlas). Although previously dorsal g1 and right ventral g1 cells were reported to fuse, results with fluorescent markers suggest that these cells remain separate (Smit et al., 2008). Gland cell morphology is sculpted by surrounding muscle cells (PhaFIG 8H) (Raharjo et al., 2011). The g1 cells extend three cuticle-lined ducts anteriorly within the narrow pharyngeal nerve cords. Two of these ducts pass through the isthmus before emptying into the pharyngeal lumen near the first bulb. The dorsal g1 duct travels much farther and empties near the anterior limit of the pharynx. The g2 cells also extend ducts, which are much shorter and empty into the lumen of the second bulb. The g1 cells contain a lamellar cytoplasm and few vesicles, whereas the g2 cells have a rather clear cytoplasm and more vesicles. These contents may vary from animal to animal, and vesicle sizes are quite large and variable. Gland cells receive motor innervation from M4 and M5 motor neurons, which suggests that they may be stimulated to secrete digestive enzymes synchronously with pharyngeal pumping activity. Periodic episodes of secretion (vesicle motion) have been seen in g1 ducts by light microscopy and are apparently associated with molting (Singh and Sulston, 1978; Hall and Hedgecock, 1991). This suggests that gland secretion may participate in the digestion of the pharyngeal cuticle during molting.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1531, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "be3afc3b-7776-4d22-bf0e-4745ddf2dc91": {"__data__": {"id_": "be3afc3b-7776-4d22-bf0e-4745ddf2dc91", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7) Pharyngeal Neurons](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "21ac2665-5bd3-455d-8059-4291b6ffc087", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7) Pharyngeal Neurons](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "7c4c412b84aa704736f598966838c1f4a71d55c6d42471018393527d367fcb79", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The pharynx has 20 intrinsic neurons of 14 types, all of which have cell bodies located in the anterior or posterior bulb (see also PharynxAtlas). Six types are bilaterally paired and eight are single neurons. These neurons extend processes anteriorly and/or posteriorly along the three longitudinal pharyngeal nerve cords (the dorsal and the right and left subventral) and form a small plexus (the pharyngeal nerve ring) within the anterior bulb where they decussate to the other side. A half-ring (the terminal bulb commissure) is made by neuronal processes more posteriorly within the anterior portion of the terminal bulb (PhaFIG 9 and PhaFIG 10). A few neurons (M1, M2 and M3) send out processes along unique routes. The M1 process runs anteriorly between the muscle and the right marginal cell until it reaches the pharyngeal nerve ring where it relocates to the dorsal nerve cord and continues traveling anteriorly in this location. Unlike other neuron processes, M2 and M3 processes do not make their dorsal turn within the pharyngeal nerve ring, but more anteriorly within the pm4 where they pierce through the pm4 as they travel towards the dorsal side to enter the dorsal nerve cord (PhaFIG 10E-J). M2 neurons make synapses to pm4 along the way.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1256, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ca633d99-ab2c-4a01-9df6-ef629a9465cd": {"__data__": {"id_": "ca633d99-ab2c-4a01-9df6-ef629a9465cd", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7) Pharyngeal Neurons](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c103f611-8107-4a39-8a1c-fd90210a72cd", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7) Pharyngeal Neurons](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "e8949033a4a3995d240d2c008edb1a99a3879f0dd5752e8f4e91027e66de92e8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Most of these processes interact synaptically with others within the pharyngeal nerve ring, formed between the narrow region where pm4 and pm5 appose each other (PhaFIG 9). These synapses are of the en passant type, similar to those seen in the somatic neurons. The pharyngeal motor neurons also form neuromuscular junctions (NMJs) onto pharyngeal muscles. Interestingly, all non-neuronal cells receive some synaptic input (Cook et al., 2019). Unlike NMJs between somatic neurons and body wall muscles, no basal lamina has been found separating the neurons from muscles in the pharynx. There are no direct contacts between pharyngeal neurons and the larger somatic nervous system except the gap junctions made between RIPL/R neurons and the pharyngeal I1s, and gap junctions between RIPL/R and the pharyngeal motor neuron, M1 (Albertson and Thomson, 1976; Avery and Thomas, 1997). Ablation of RIP cells results in only a minor effect on pharyngeal function such that the brief inhibition of pumping in response to light touch to body disappears (Avery and Thomas, 1997). It is possible that one or more pharyngeal neurons, such as NSM cells, could secrete hormonal factors into the pseudocoelom to influence the rest of the animal. Otherwise, pharyngeal and somatic nervous systems function more or less independently of each other. A dissected and isolated pharynx continues its normal pumping behavior (Avery et al., 1995).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1425, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "021b2219-011e-4edc-9010-5ab9c71746bc": {"__data__": {"id_": "021b2219-011e-4edc-9010-5ab9c71746bc", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7) Pharyngeal Neurons](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7748b49a-cbe2-4c01-9ffa-98df6029d7f9", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7) Pharyngeal Neurons](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "31a1565857c02904becbc38b42a5c22eeb0d07109ed3ccb4ba6fb9e3d75f7d92", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In fact, generation of electrical potential changes required for pharyngeal pumping is probably intrinsic to the pharyngeal muscle cells themselves since pumping behavior continues even when all the pharyngeal neurons are ablated (Avery and Horvitz, 1989). Although pumping can still occur after complete ablation of the pharyngeal nervous system, four of the pharyngeal neurons, MC and M3 motor neuron pairs, are important for the regulation of the pump motion.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 462, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "208ba4b2-fd72-49be-8d7d-871e2e94efc9": {"__data__": {"id_": "208ba4b2-fd72-49be-8d7d-871e2e94efc9", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7) Pharyngeal Neurons](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f4a15e36-0da9-4ab5-bf98-e1d50cf8a483", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7) Pharyngeal Neurons](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "af7a1afd4d398e46b04a73f62d1228a6d6b2828b6095dae208ce2cd435683768", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Pharyngeal neurons fall into three categories: motorneurons, interneurons and other neurons. However, this distinction is somewhat arbitrary because most of these neurons have structures that suggest mixed functions.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 216, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5f0c5640-84c5-4e4a-9abb-bfc1bcb0b719": {"__data__": {"id_": "5f0c5640-84c5-4e4a-9abb-bfc1bcb0b719", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7) Pharyngeal Neurons](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9062c34f-3239-459a-8eef-86e79ca90a17", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7) Pharyngeal Neurons](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "0b4884f7efc5b3162c20644a9fcbab0742034cc44b2fac056544f943316b6264", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "7.1 Pharyngeal Motor Neurons", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 28, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "19b05854-0870-47e3-bd9b-2a26790e8f51": {"__data__": {"id_": "19b05854-0870-47e3-bd9b-2a26790e8f51", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7.1) Pharyngeal Motor Neurons](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "faa976ea-0e76-4065-905c-984be1b01a7a", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7.1) Pharyngeal Motor Neurons](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "0645cb7c7a0a3144526c4519b1818d1526d0abdee04eac5798f6cd39833bffde", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "7.2 Interneurons", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 16, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e56f1ac3-5a9c-40e3-9449-408de5575c68": {"__data__": {"id_": "e56f1ac3-5a9c-40e3-9449-408de5575c68", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7.2) Interneurons](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fcc426cf-74ef-4c1f-a43a-f0915b8c729e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7.2) Interneurons](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "fc582505b85d52b997388c5460aa7a92d5b6be7bdc000114d02e0617fe471f4a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "I1, I2, I3 and I6 are unbranched bipolar cells. I1 cells make electrical synapses with the somatic neurons RIPL/R and synapse onto MC neurons. I5 is a fairly complex cell, the processes of which make a circle within the pharyngeal nerve ring. All of these neurons except for I4 have free subcuticular endings that may have proprioceptive function (Cook et al., 2019). See PharynxAtlas for more details.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 402, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "78a3a7cb-1dd1-4bf6-8bf0-055978b8c276": {"__data__": {"id_": "78a3a7cb-1dd1-4bf6-8bf0-055978b8c276", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7.2) Interneurons](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3ff55160-18dd-4512-b9d6-6745b546de76", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7.2) Interneurons](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "c251a854b19e176be15bac381f71ffd0b4e9780afa97df2840721257c4f90274", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "7.3 Sensory Neurons", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 19, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "38f1abd1-6992-4df0-82c1-0e5074a3cb5d": {"__data__": {"id_": "38f1abd1-6992-4df0-82c1-0e5074a3cb5d", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7.3) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b6af7bea-c1a3-49a6-bb9d-f0d08fc01f33", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7.3) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "474557edb8f6244375b848b2b3b1c0f53402a7c65e7caeaa5deec5493d8c9055", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Rudimentary sensory adaptions have been found in most pharyngeal neurons, although none form true cilia (Albertson and Thomson, 1976; Cook et al., 2020). These specializations mean that almost all neurons of the pharynx are truly polymodal. Most sensors are localized to prominent internal structures along the alimentary canal, probably helping to detect progress of food items (bacteria) as they proceed down the buccal channel towards the intestine (PhaFIG 11). Other sensors are embedded inside individual muscle cells and likely provide proprioceptive feedback by detecting muscle contractions during the feeding rhythm.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 625, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6a36c6df-f3e7-4970-9957-0724737fe6a5": {"__data__": {"id_": "6a36c6df-f3e7-4970-9957-0724737fe6a5", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7.3) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "05b16338-364c-44c8-a40b-ff7c4ce2c2ab", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7.3) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "c7c95c6d81a381a61982475f748e7644d8f0c294b730fb7226ec68c83527e637", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Three \u0093interneurons \u0093 I1, I2 and I3 form sensory structures in close association to the flaps, at the entry point to the buccal channel, and some are exposed to the channel contents. The MC cell forms an unexposed sensory structure close to the sieve, while the NSM neurons each have an exposed sensory structure there (PhaFIG 11). The NSM ending expresses an Acid-Sensing Ion Channel (ASIC), DEL-7, at this structure. This channel may allow contents of the buccal channel to directly influence physiological activity of NSM (Axang et al., 2008; Rhoades et al, 2019).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 567, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "14e5afa2-91a5-4f20-89cd-c3eb05171165": {"__data__": {"id_": "14e5afa2-91a5-4f20-89cd-c3eb05171165", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7.3) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "66ef5a13-a204-403e-a55f-8ca6a92baaaa", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7.3) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "0515c3b2c70fdedbac1c7c19f8f71f49422d9d146e3cc95005e28b2fab11678c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "M3 and M4 neurons form exposed structures along the buccal channel near the isthmus.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 84, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ccdc0010-9a4a-4326-95fa-1d8eab1447c0": {"__data__": {"id_": "ccdc0010-9a4a-4326-95fa-1d8eab1447c0", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7.3) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5dbd862b-8b69-4efd-b8e1-0d475f8a0f05", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7.3) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "bc1f09757d0d818839b4dad1f345e823b8dba7819249dcb8d59991dc33f1c9b6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "I6 and the M5 cell each have apparent sensory structures associated with the grinder.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 85, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2d16c3b8-2575-45b1-b163-516200da8ba7": {"__data__": {"id_": "2d16c3b8-2575-45b1-b163-516200da8ba7", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7.3) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7927f720-1f7b-4fe5-bc11-41253d9e07c2", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7.3) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "c084d33646219aba927aa14a6443e5f2df96b320fba94d048fddd23f8578fe51", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The I5 neuron has a sensory ending buried deep inside a muscle cell in the second bulb, providing a proprioceptive cue during bulb contractions.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 144, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e30639d2-7d95-45e0-8311-e1340b82c494": {"__data__": {"id_": "e30639d2-7d95-45e0-8311-e1340b82c494", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7.3) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "363702aa-16da-447b-9b20-d7fa21feaa3e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7.3) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "8cd5c3023f71322c7bbb7a8f294aba668f228c08794c2faf8de646535a9425a9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "None of these pharyngeal sensors constitutes a true cilium, as they all lack features like an axoneme, Y-links or a microtubule-filled extension. Instead, these structures feature prominent adherens junctions that strongly link a short, block-like dendritic ending to the surrounding cells. Where the ending lies directly against the pharyngeal luminal cuticle it is referred to as an \u0093exposed\u0094 ending (exposed to the lumen of the pharynx). If the ending lies somewhat away from the phayrnx\u0092s internal cuticle, it is referred as an \u0093unexposed\u0094 ending (if still close to the lumen) or a \u0093buried\u0094 ending (if far from the lumen). These endings were originally listed in Table 1 in Albertson and Thomson (1976).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 707, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5d052148-2cb6-488e-af51-f2a461843b52": {"__data__": {"id_": "5d052148-2cb6-488e-af51-f2a461843b52", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7.3) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9bb83c9c-e97c-422c-8374-f28df46da44e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7.3) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "440a6bcb51e81c45b2cef6b3c1c00dc04a0940fb7a958eb955b0dcb9ec20e9ab", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "7.4 Pharyngeal Connectome", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 25, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a3bae0c0-9fac-4688-aadb-683d5195894e": {"__data__": {"id_": "a3bae0c0-9fac-4688-aadb-683d5195894e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7.4) Pharyngeal Connectome](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c9ec3510-2c4f-4d35-beb9-eccd205f344d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7.4) Pharyngeal Connectome](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "73a6bd6bd41cb75493ac359ed12acd556662915d8d40bdd953beaa0035242421", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The synaptic connectivity among the pharyngeal neurons and muscles is virtually independent of the somatic nervous system, except for a few contacts via the RIP neurons of the nerve ring. The complete set of synaptic connections (chemical and electrical) within the pharynx was substantially augmented by Cook et al., (2020). Many more synapses were added, and the previous wiring documented by Albertson and Thomson (1976) was verified. Virtually every cell in the pharynx of any type is now known to be included in this local circuitry. Re-analysis of the revised connectome has revealed how those circuits can be parsed into several distinct modules that match known stages in pharyngeal behavior: 1) pumping, 2) neuromodulation, 3) peristalsis, and 4) grinding (Cook et al., 2020) (PhaFIG 11).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 797, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4917af8f-8ba5-4c63-a3f4-69b487853f13": {"__data__": {"id_": "4917af8f-8ba5-4c63-a3f4-69b487853f13", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7.4) Pharyngeal Connectome](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8569a765-4bed-4cd7-840e-619a239cb14b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7.4) Pharyngeal Connectome](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "7878775bf89f86ff3ce7a2eca253d0e9856f8b13c940f82409a3bd6515fcd328", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "It is also interesting that the neuropeptides and receptors that interconnect the pharyngeal neurons appear to be somewhat separate from the peptidergic system of the somatic nervous system (see Figure 5 in Beets et al, 2023). There are exceptions: for instance the common FRPR-7 receptor proteins expressed in many pharyngeal neurons, are responsive  to the FLP-1 ligand released by the AVK neurons of the nerve ring. Several classes of pharyngeal neurons also produce neuropeptide ligands that principally target somatic neurons (Beets et al, 2023). These peptidergic connections tend to operate at a distance, and do not require close contact, nor do they shadow the chemical and electrical wiring of the nervous system.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 723, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "304523ff-d4ac-4a99-a1f6-3b6778165993": {"__data__": {"id_": "304523ff-d4ac-4a99-a1f6-3b6778165993", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7.4) Pharyngeal Connectome](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ce6c101f-1d00-4f7d-b1d8-8a83e2467f4b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7.4) Pharyngeal Connectome](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "5620cd97a7c85ec38e7f823d93984fbbd95b30eb575824b2b851d7def1d458b1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "7.5 Other Neurons", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 17, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "043f570f-5ca5-436c-9a11-b15b8152cb1f": {"__data__": {"id_": "043f570f-5ca5-436c-9a11-b15b8152cb1f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7.5) Other Neurons](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ce0a62a9-5a3b-48ff-9413-49896eda1fa4", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 7.5) Other Neurons](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "e0cb8f09843459f7e62b628c5875244906b4070ade623d6594dbebbd4de8ad27", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "MC neurons are a pair of bipolar cells situated within the anterior bulb that make chemical synapses exclusively onto marginal cells (Cook et al., 2019). The motor-interneuron, MI, is a single unipolar cell situated in the dorsal side of the anterior bulb and synapses onto both muscle and other neurons. The neurosecretory-motor neurons NSML and NSMR send out branches that form varicosities and contain mixed-sized vesicles (PhaFIG 9). The two main processes of the NSMs run in close apposition to the pseudocoelom over most of their length and form some release sites towards this space. NSMs are serotonergic. These cells may have both neurosecretory and motor functions and may communicate the presence of food to the rest of the animal's body. Exogenous application of serotonin stimulates pumping, decreases locomotion and stimulates egg-laying (Horvitz et al., 1982). The same responses are seen in the presence of bacteria in the environment. NSMs were thought to be potential candidates for mediating the effects of endogenous serotonin. However, ablation of NSMs has only subtle effects on pumping, suggesting that they may be redundant for this function (Avery et al., 1993, Avery and Thomas, 1997). The slowing of locomotion in the presence of bacteria becomes more enhanced in animals that were previously food-deprived, compared to well-fed animals. This phenomenon is described as \"the enhanced slowing response.\" When NSMs are ablated there is a small but significant decrease in this enhanced slowing of locomotion, which suggests NSMs contribute to this behavior (Sawin et al., 2000).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1603, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "68453989-968b-49c7-bf19-c3d8a3786317": {"__data__": {"id_": "68453989-968b-49c7-bf19-c3d8a3786317", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 8) Pharyngeal-Intestinal Valve (VPI)](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1cd2c544-44fa-4ecf-8721-f2d17d9c4f95", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 8) Pharyngeal-Intestinal Valve (VPI)](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "efe3fa9cf109d18982b9109217aeb10c995ed1ea09832b3a7697dd0a6fad8d58", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "No apparent muscular elements operate within the valve cells, nor are there any muscles attaching to this valve from the outside. Thus, the valve is probably a passively open and patent channel at all times, but rather narrow in caliber. The pm8 muscle of the pharynx is in appropriate position to act alone as a sphincter just rostral to the valve cells, but pm8 shows no direct innervation (Albertson and Thomson, 1976; Cook et al., 2019). Contraction of the pm8 has been suggested to open the valve wider when the grinder is active (Avery and Thomas, 1997).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 560, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7141abf0-149e-44a5-ad8e-3ac667810e0e": {"__data__": {"id_": "7141abf0-149e-44a5-ad8e-3ac667810e0e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 8) Pharyngeal-Intestinal Valve (VPI)](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3ffc97ea-d3d1-4c37-b343-3f05255ddc59", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 8) Pharyngeal-Intestinal Valve (VPI)](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "91f80cef13280edb4d6e7ed713ca163897b96e3df1ea881d2b2e476e2ebd8188", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Each valve cell has an electron-dense cytoplasm and occupies a thin wedge-shaped domain surrounding about one half of the lumen of the valve (PhaFIG 12). The nuclei of valve cells are flattened in shape, and the cytoplasm contains radial bands of intermediate filaments anchoring the apical cuticle to the basal lamina of the epithelium via hemidesmosomes, again in a very similar fashion to those seen in the buccal epithelium (D.H. Hall, unpublished).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 453, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f1be76c9-c1c0-4b73-94b7-e04b760c9170": {"__data__": {"id_": "f1be76c9-c1c0-4b73-94b7-e04b760c9170", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 9) Specific Structures Within the Pharynx](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c7ddce55-7e52-47cf-9bfc-0ba6ce02e6b5", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 9) Specific Structures Within the Pharynx](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "f124c53aab27ebbf9d6d31a558a49ec7a5f465eeaefbe910781648d8cbcc3b13", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "9.1 Channels of the Pharyngeal Lumen", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 36, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4c6b0fad-bcf1-4b19-b502-e1ed9abd8f24": {"__data__": {"id_": "4c6b0fad-bcf1-4b19-b502-e1ed9abd8f24", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 9.1) Channels of the Pharyngeal Lumen](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0dda97c2-c0dc-4e1b-be92-1fa2b4043a38", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 9.1) Channels of the Pharyngeal Lumen](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "867571af84794f2421c2c62b3f02aafb75d29882220760c8f01746c3f0cb4ec8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Radial channels, three narrow grooves in outer corners of the pharyngeal cuticle, are located in both the anterior procorpus and anterior isthmus (PhaFIG 2) (Albertson and Thomson, 1976). The channels allow an escape route for liquid to be regurgitated out of the pharynx via the buccal cavity. This results in food particles being trapped in the central lumen while fluid is expelled through the channels (Fang-Yen et al., 2009).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 430, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8f3c6343-d19d-4247-b79d-6307cfa51745": {"__data__": {"id_": "8f3c6343-d19d-4247-b79d-6307cfa51745", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 9.1) Channels of the Pharyngeal Lumen](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d350ca8d-a35f-4339-b6ba-28dabd761477", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 9.1) Channels of the Pharyngeal Lumen](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "ef9135bb341ea3fb8eca243cbd8dfe9d7a2b5213a1a56b897db46faf7bdf4198", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "9.2 Cuticle of the Pharynx", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 26, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7298fa8a-36fa-44cc-997e-45cba06fbe5c": {"__data__": {"id_": "7298fa8a-36fa-44cc-997e-45cba06fbe5c", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 9.2) Cuticle of the Pharynx](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1e216ab8-6dff-421f-988f-a6906186332f", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 9.2) Cuticle of the Pharynx](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "751ffffaf91cc36050e5de985fedcd6d65ea4f9de766626c8b59dcc93f018416", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "A thin cuticle lining extends to cover the interior surface of the pharyngeal passageway from the lips to the back of the pharynx, ending at the rear of the pharyngeal-intestinal valve (PhaFIG 2). The pharyngeal cuticle is formed by the pharyngeal epithelium and the muscle cells to cover the apical surfaces of many cells acting in concert, much as the thickened pharyngeal basal lamina is formed jointly on basal surfaces of the pharyngeal cells. Unlike the body cuticle (see Hermaphordite Cuticle), this cuticle shows no layers; however, it shows some reinforcement at points of stress. For instance, it becomes keratinized to stain more densely by TEM at certain regions. Other specialized portions of the pharyngeal cuticle include the following.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 751, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c5ebadae-2ce9-4e2c-8b62-294b444ca84f": {"__data__": {"id_": "c5ebadae-2ce9-4e2c-8b62-294b444ca84f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 9.2) Cuticle of the Pharynx](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "62a80a7b-cd5a-40c1-a66a-99bb5b05edb7", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 9.2) Cuticle of the Pharynx](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "e0e0e409a1b697e1b7ba1eea6dbf7395d7649441cdba7dc0be98ec974f177c50", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "9.2.1 Bridging Cuticle", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 22, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ef237600-b3c0-4019-8c91-d85cbef910d0": {"__data__": {"id_": "ef237600-b3c0-4019-8c91-d85cbef910d0", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 9.2) Cuticle of the Pharynx](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "93c2a0ff-5ff6-4219-a7f5-392e1140f0d6", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 9.2) Cuticle of the Pharynx](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "3fc7d540d847847974a98ea014c249cca76e69d7ad4a0cffe0cd31f50377e9fb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "A small discrete region of cuticle connects the body wall cuticle covering the lips to the cuticle lining the buccal cavity. This bridging cuticle lies on the outer face of the anterior arcade and may also be touched briefly by the posterior arcade (see Epithelial System - Interfacial Cells; InterFIG 1).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 305, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b90c9782-fc3c-4584-93df-56e0adacfcd6": {"__data__": {"id_": "b90c9782-fc3c-4584-93df-56e0adacfcd6", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 9.2) Cuticle of the Pharynx](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d1514488-8fea-41d2-a005-923ca854039d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 9.2) Cuticle of the Pharynx](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "8541495b5cb9aacbb7e7625db4e17b6b9ec7e0eea8482d842f1356436ae46055", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "9.2.2 Flaps", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 11, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2925f8f2-46f4-4076-b60e-6bcef9af499d": {"__data__": {"id_": "2925f8f2-46f4-4076-b60e-6bcef9af499d", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 9.2) Cuticle of the Pharynx](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2435d422-5f46-466e-b304-886c78326740", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 9.2) Cuticle of the Pharynx](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "7e260498228d6de7925c8b27a7c8fbafc5c832cbc57198f4161ec99e3ba04919", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The metastomal flaps are cuticular projections at the base of the buccal cavity and may correspond to the onchia or buccal teeth described in other nematode species (Chitwood and Chitwood, 1950; Theska and Sommer, 2023; see also PhaFIG 2; PhaFIG 5; InterFIG 1). Three flaps extend inward from the level of from the pharyngeal muscle cells pm1 and pm2 to restrict the intake rate of bacteria at the rear of the buccal cavity (Fang-Yen et al., 2009). The flap cuticle is very electron dense, suggesting a sclerotic hardening to stiffen the flaps and the entryway to the true pharynx.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 581, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "db7e44b5-e4f4-4f5f-a38d-6ebe54651f31": {"__data__": {"id_": "db7e44b5-e4f4-4f5f-a38d-6ebe54651f31", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 9.2) Cuticle of the Pharynx](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "af7194be-987b-4556-b042-c6c5fca42141", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 9.2) Cuticle of the Pharynx](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "211f0e3854ab11ccd4e26d3b5d5941f8b4ee1f1a0492b97dc6b10b34f76637b9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "9.2.3 Grinder", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 13, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "44a464d2-2938-41b0-9819-c77731f405fc": {"__data__": {"id_": "44a464d2-2938-41b0-9819-c77731f405fc", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 9.2) Cuticle of the Pharynx](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "511285b3-8bde-4997-89ed-0ee0e79e4173", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 9.2) Cuticle of the Pharynx](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "93c73b6e78a0c7101577ae53dd626c18f342437949de4e4d984392b3e337ae28", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The grinder (PhaFIG 2) is a cuticle specialization with five distinct layers (Sparacio et al., 2020). Its three contact zones, made by the three pairs of muscle cells, rotate when the muscles contract (Avery and Thomas, 1997). The food caught and ground up between the teeth is passed back to the intestine through the pharyngeal-intestinal valve. Relaxation of the terminal bulb returns the grinder to its resting state. The grinder is made primarily by pm6 and pm7 muscles, which produce large quantities of secretory vesicles during periods of lethargus when the grinder is rebuilt (Sparacio et al., 2020). During the initial breakdown, pm6 and pm7 vesicles have an electron dense appearance, whereas later during the reformation of the new grinder most vesicles have an electronlucent appearance suggesting distinct enzymes for the absorption and building of the grinder structure. Its three contact zones, made by the three pairs of muscle cells, rotate when the muscles contract (Avery and Thomas, 1997). Although the pm6 muscle filaments are oriented in radial fashion to the grinder, some portions of the pm7 muscles are oriented obliquely to the anterior-posterior axis and are anchored on the basal pole to the rear of the terminal bulb. During lethargus, the muscle striations appear to be interrupted suggesting a temporary differentiation from a muscular to a secretory cell type. The pm6 and pm7 muscle fibers pull from the posterior side of the teeth, and coordinated action of these muscles may then rotate the grinder segments and force the teeth to scrape past and engage one another.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1602, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "57beecd2-9405-4a0a-927b-a7b1f482e233": {"__data__": {"id_": "57beecd2-9405-4a0a-927b-a7b1f482e233", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 9.2) Cuticle of the Pharynx](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6dfb0b03-be17-4cdf-9685-814358a421b3", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 9.2) Cuticle of the Pharynx](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "bac79794286f90d21bdb4e5dbd5726154fcf40dc9b6d4c636d2342ad2fa313fe", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "9.2.4 Pharyngeal Sieve", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 22, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3b0010a2-97c4-4b16-bd31-37d9a389a446": {"__data__": {"id_": "3b0010a2-97c4-4b16-bd31-37d9a389a446", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 9.2) Cuticle of the Pharynx](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "509345e5-4c96-4a63-9457-c24359cfaf7c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 9.2) Cuticle of the Pharynx](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "a68df4c95e540dff99486966c71cf0aec0ad8ff41fc29dca12071b143756d3dd", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "These finger-like extensions from the pharyngeal cuticle probably act to trap bacteria, just posterior of the metacorpus (Fang-Yen et al., 2009; PhaFIG 2). They extend from the cell borders where pm4 muscles meet the neighboring mc1 cells. They project over a region of about 20 \u03bcm in length within the narrow lumen, ending near the transition of the metacorpus to the isthmus.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 377, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "30453c91-a2c4-4e2d-8ada-41a6f99dc97f": {"__data__": {"id_": "30453c91-a2c4-4e2d-8ada-41a6f99dc97f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 9.2) Cuticle of the Pharynx](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "af3fa76a-b19a-4fcf-8f80-1754446f7e36", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 9.2) Cuticle of the Pharynx](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "1eac676033d9353594b5569d7ff2bde853450454b01225b2ccdaa0348e50fb9c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "9.3 Gap Junctions (see also chapter on Gap Junctions)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 53, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c7d3693f-0715-497f-8c76-4dfa90688cfb": {"__data__": {"id_": "c7d3693f-0715-497f-8c76-4dfa90688cfb", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 9.3) Gap Junctions](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b78bd0cd-c357-4ee8-b8ac-73977fcceae6", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 9.3) Gap Junctions](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "719b32779dfe420b41d506f9f05beb1261d5fa36ee74066c6d8a140fbe01e9ca", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The muscle cells and the marginal cells of the pharynx are linked to and communicate with each other via elaborate gap junctions (Phelan, 2005; Altun et al., 2009; Bhattacharya et al., 2019; see also PhaFIG 7; PhaTABLE 1). Gap junctions also exist between the pharyngeal neurons and also between the pharyngeal neuron I1 and the extrapharyngeal neuron RIP. Gap junctions within the pharynx are composed of innexins, invertebrate gap junction proteins. Innexins heteromerically assemble into hexameric hemichannels and form pores between cells. This gap junction network confers a high level of connectivity within the pharynx, which is essential in coordinating waves of muscle contractions and spreading the neuronal input.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 724, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9facc4c2-ba0d-4cbf-870e-13e333e34f3e": {"__data__": {"id_": "9facc4c2-ba0d-4cbf-870e-13e333e34f3e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 10) Feeding Behavior](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e617afc8-d3e1-4849-aaf9-73f4d7f549a7", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 10) Feeding Behavior](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "89783e6c692ef7bd0dcb19e95684bd02556db34f2f138b2339943f64912ea142", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "C. elegans is a filter-feeder. Particles (bacteria) are taken in as suspended in liquid and then trapped in the pharynx while the liquid is expelled outside by the function of the corpus and anterior isthmus (Avery and Thomas, 1997; Avery and Shtonda, 2003). The particles are then transported to the terminal bulb, ground and passed into the lumen of the intestine. The feeding behavior consists of two motions; pumping, a contraction-relaxation cycle involving the corpus, anterior half of the isthmus and terminal bulb; and posterior isthmus peristalsis. Pumping involves near-simultaneous contraction of the muscles of the corpus, anterior isthmus and terminal bulb followed by near-simultaneous relaxation. When a feeding motion begins, contraction of the corpus and anterior isthmus opens their lumens, sucking particles and liquid in, whereas contraction of the terminal bulb muscles breaks up already-trapped bacteria and passes the debris posteriorly towards the intestine (Avery and Shtonda, 2003). At this stage corpus and anterior isthmus are separated hydrodynamically from the terminal bulb by a closed isthmus. During the relaxation period that follows, the lumens of the corpus and the anterior isthmus close, allowing for the liquid to be expelled through the radial channels while bacteria are retained and the grinder returns  to its resting position (Fang-Yen et al., 2009). Food particles are trapped at two locations: the anterior procorpus and anterior isthmus. At each location, early relaxation of the pharyngeal lumen just anterior to the trap location prevents particles from exiting the trap (Fang-Yen et al., 2009). When the muscles again contract, the bacteria are carried further posteriorly by the inflow of liquid. Roughly one out of four pumps is followed by a posterior isthmus peristalsis where the trapped bacteria are carried from the anterior isthmus backwards to the grinder. Although each pm5 muscle cell runs the entire length of the isthmus, peristalsis occurs as a wave that propagates from anterior to posterior instead of simultaneously along its length. This capacity of isthmus for asynchronous contraction is suggested to permit the terminal bulb and corpus lumen to be at different pressures (Avery and Thomas, 1997).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2267, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "27573059-4307-4a80-946e-26e4fd5b4ac6": {"__data__": {"id_": "27573059-4307-4a80-946e-26e4fd5b4ac6", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 10) Feeding Behavior](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f58fc4af-bffb-4337-97c8-5160b651c535", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 10) Feeding Behavior](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "e0121891a9fdede204b950e4003adb1ed6069831589d452d49cace5c0a6947e6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Neural control of feeding has been elucidated through both neuronal ablation and optogenetic manipulation of neuron activity (Avery and Horvitz, 1989; Trojanowski et al., 2014). Interestingly, pumping continues even after ablation of all pharyngeal neurons, albeit at a highly reduced rate (Avery and Horvitz, 1989). However, elimination of cholinergic signaling leads to a complete loss of pumping (Avery and Horvitz, 1990; Alfonso et al., 1993).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 447, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a900993d-6816-4b51-915d-0350593ec37a": {"__data__": {"id_": "a900993d-6816-4b51-915d-0350593ec37a", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 10) Feeding Behavior](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b7c0e4d5-9644-4a91-92f1-ae1ccaebf9b4", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 10) Feeding Behavior](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "2a716b567f3bfbff67de0c312cf3fafc7614c5a121d992104f33c8783f7b1012", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Isthmus peristalsis is controlled by M4. Ablation of M4, which innervates the isthmus and terminal bulb muscles, leads to faulty isthmus peristalsis and a \u0093stuffed\u0094 worm appearance where food remains stuck in the isthmus, eventually leading to starvation (Avery and Horvitz, 1989). M4 also plays a minor role in pumping with optogenetic excitation of M4 leading to an increase in the pumping rate. Conversely, optogenetic inhibition or ablation of M4 causes a decrease in the pumping rate (Raizen et al., 1995; Trojanowski et al., 2014).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 537, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "008fe413-32de-4312-9d1b-9994bfdb6d98": {"__data__": {"id_": "008fe413-32de-4312-9d1b-9994bfdb6d98", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 10) Feeding Behavior](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "adb4bd69-068c-45bd-a1db-13752060de72", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 10) Feeding Behavior](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "10c035859761d6f55492f67aad9faab4186345f183a74dc0906032b3f7496338", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The rate of pumping is controlled by the MC, M2, and M4 motor neurons (Avery and Horvitz, 1989; Trojanowski et al., 2014). The I1 neurons, which make the only connection to the somatic nervous system, regulate pumping via the MC and M2 neurons. The MC, M2 and M4 neurons are cholinergic excitatory motor neurons (Raizen et al., 1995; Keane and Avery, 2003). Mutants in which acetylcholine synthesis (cha-1) or packaging (unc-17) is disrupted show a pumping defect similar to that seen after MC ablation. Functional studies suggest that MC neurons synapse onto pm4 and that synaptic transmission from MC neurons to pm4 requires the nicotinic acetyl-choline receptor (nAChR) subunit, EAT-2 to be expressed on pm4. MC neurons may also be mechanosensory, because they have free endings at the boundary between the procorpus and metacorpus and may sense the presence of bacteria in the pharynx.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 889, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0bc95837-e967-4c25-a6b6-7092b6bcae3f": {"__data__": {"id_": "0bc95837-e967-4c25-a6b6-7092b6bcae3f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 10) Feeding Behavior](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d952b2b8-6c9e-4ade-80f4-5eebe2838d79", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 10) Feeding Behavior](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "3351962809fe37efbdff912454b46b2873633679c6b9f98785dbea685ebaf4ea", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Pumping is suppressed during dauer, lethargus, and in response to a touch stimulus in adults. As described above, the latter response depends on an RIP/I1 connection. This circuit may also be important for suppression of pumping in the dauer larva (Keane and Avery, 2003). Inhibition of pumping during the dauer stage may save energy and prevent ingestion of environmental toxins when no appropriate food is available.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 418, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0433b580-64d1-4b24-883c-a6fb93177e32": {"__data__": {"id_": "0433b580-64d1-4b24-883c-a6fb93177e32", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 10) Feeding Behavior](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "dbc43d84-f74b-4143-96e5-0b137f2aabc7", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 10) Feeding Behavior](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "26231014ab488900caf9c5fb173ccad714accfc07fb59df7c9255914094115b7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Feeding behavior is also impacted by exposure to light (Bhatla and Horvitz, 2015; Bhatla et al., 2015). Following exposure to light, feeding is inhibited and a subsequent reversal of flow in the pharynx leads to expulsion of bubbles (\u0093spitting\u0094) from the mouth. Light-induced inhibition of feeding acts through both the I2 neurons and the RIP/I1 connection. The I2 neurons, which were originally classified as interneurons, also synapse directly onto pharyngeal muscle (Bhatla et al., 2015; Cook et al., 2019). Spitting behavior is controlled by M1, which may continuously contract the pm3 muscles allowing for pharyngeal contents to escape during the reduced pumping.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 668, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b4b62245-154d-43fb-a8d5-0a93636091cc": {"__data__": {"id_": "b4b62245-154d-43fb-a8d5-0a93636091cc", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 11) List of Pharyngeal Cells](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f21e0871-3ebc-4b49-9c98-b7f1b66a5747", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 11) List of Pharyngeal Cells](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "4503cb8f7879c70d7808ffab3862ae7880214424deaa14a57ff40e068b539435", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "i. Buccal epithelium of the pharynx (e)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 39, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6a63641b-9d38-4dd9-8c48-32382b21f14d": {"__data__": {"id_": "6a63641b-9d38-4dd9-8c48-32382b21f14d", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 11) List of Pharyngeal Cells](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1909294f-dc2f-4523-89e6-3c3b8928e3f9", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 11) List of Pharyngeal Cells](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "bc0fc9638d12d79edfe20205fdd905dced08810c0e8d09949c75c5fbb6a9cdd7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "ii. Pharyngeal muscles (pm). Note that in earlier publications these cells are labeled as \"m\"; m1, m2, m3 etc., but here they are labeled \"pm\" for \"haryngeal uscle\" (Avery and Thomas, 1997).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 190, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e42208bb-9e7f-41c9-84e7-cbd729c12c5a": {"__data__": {"id_": "e42208bb-9e7f-41c9-84e7-cbd729c12c5a", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 11) List of Pharyngeal Cells](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4f5a2c1b-564f-4f50-9362-9a0d2af33e02", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 11) List of Pharyngeal Cells](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "73bf8aa7a388ffbc4a53b2cf229e095fa10054ce2144ffd7b69aa49725f2c571", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "1. First pharyngeal muscle ring; all fuse into one syncytium around hatching\n\npm1DL\n\npm1DR\n\npm1L\n\npm1R\n\npm1VL\n\npm1VR\n\n2. Second pharyngeal muscle ring\n\npm2DL; fuses with DR around hatching\n\npm2DR; fuses with DL around hatching\n\npm2L; fuses with VL around hatching\n\npm2R; fuses with VR around hatching\n\npm2VL; fuses with L around hatching\n\npm2VR; fuses with R around hatching\n\n3. Third pharyngeal muscle ring\n\npm3DL; fuses with DR around hatching\n\npm3DR; fuses with DL around hatching\n\npm3L; fuses with VL around hatching\n\npm3R; fuses with VR around hatching\n\npm3VL; fuses with L around hatching\n\npm3VR; fuses with R around hatching\n\n4. Fourth pharyngeal muscle ring; all fuse into one syncytium around hatching\n\npm4DL;\n\npm4DR;\n\npm4L;\n\npm4R;\n\npm4VL;\n\npm4VR;\n\n5.Fifth pharyngeal muscle ring; all fuse into one syncytium around hatching\n\npm5DL;\n\npm5DR;\n\npm5L;\n\npm5R;\n\npm5VL;\n\npm5VR;\n\n6. Sixth pharyngeal muscle ring\n\npm6D\n\npm6VL\n\npm6VR\n\n7. Seventh pharyngeal muscle ring\n\npm7D\n\npm7VL\n\npm7VR\n\n8. Eighth pharyngeal muscle ring\n\npm8", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1026, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a4c7166b-fedf-4f71-a030-cc0ce5a6ebb9": {"__data__": {"id_": "a4c7166b-fedf-4f71-a030-cc0ce5a6ebb9", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 11) List of Pharyngeal Cells](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "34dde14e-8555-46b3-9ae3-6cfb24c9e696", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 11) List of Pharyngeal Cells](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "b30c2d196eb8ebb62bcdb21eb13104cb73e6a0ae94757b07f1bf2d898778dbfa", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "iii. Marginal cells (mc)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 24, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "21d9224a-6ae1-4b85-be6e-2c2b4fce2248": {"__data__": {"id_": "21d9224a-6ae1-4b85-be6e-2c2b4fce2248", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 11) List of Pharyngeal Cells](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "88a664f2-176a-4c04-a1de-9048b940004d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 11) List of Pharyngeal Cells](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "5710348a3cfac78e5dedcf56dd78d8c064b3695669b4dd8dc0b7f439741ff8b4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "1. First marginal cell ring\n\nmc1DL\n\nmc1DR\n\nmc1V\n\n2. Second marginal cell ring\n\nmc2DL\n\nmc2DR\n\nmc2V\n\n3. Third marginal cell ring (syncytial, cells fuse around hatching)\n\nmc3DL\n\nmc3DR\n\nmc3V", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 186, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "62260e83-be25-4aad-b987-f34cf54ab3b4": {"__data__": {"id_": "62260e83-be25-4aad-b987-f34cf54ab3b4", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 11) List of Pharyngeal Cells](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "20c27b0b-c2b1-4897-87a6-12ba6b0c5abb", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 11) List of Pharyngeal Cells](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "119c7c6f39749d766667f90d6b320d2932b628d7ea48f3d25e5cf4d3cacfaf9d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "iv. Pharyngeal-intestinal valve (vpi)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 37, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b3e3e5c2-2076-46a9-b5d8-bad3f37f8bfa": {"__data__": {"id_": "b3e3e5c2-2076-46a9-b5d8-bad3f37f8bfa", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 11) List of Pharyngeal Cells](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "acbf4450-bacf-452a-81d7-29d4dc63b114", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 11) List of Pharyngeal Cells](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "df28cdb33623848097b96c75767bdbe509aecf4ee31bc4c8df5165f012d5d853", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "1. First pharyngeal valve ring\n\nvpi1\n\n2. Second pharyngeal valve ring \n\nvpi2DL\n\nvpi2DR\n\nvpi2V\n\n3. Third pharyngeal valve ring\n\nvpi3D \n\nvpi3V", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 140, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a84728a8-9df7-4745-beaa-785b98f0f206": {"__data__": {"id_": "a84728a8-9df7-4745-beaa-785b98f0f206", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 11) List of Pharyngeal Cells](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "10540d88-173c-4f99-9a21-7a7529318e68", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 11) List of Pharyngeal Cells](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "019cd3ee0e0ef299ae1ac0036aada6dd92533ef3839799ca4ca1b7c8c2967e64", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "v. Pharyngeal neurons", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 21, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0bfe05bb-accb-47b4-8f87-b45cdd64595f": {"__data__": {"id_": "0bfe05bb-accb-47b4-8f87-b45cdd64595f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 11) List of Pharyngeal Cells](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4008df65-1cff-4d9a-a6c7-badf0d197fec", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 11) List of Pharyngeal Cells](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "5113e29997e7499f937c3a7a6af2817d953f758d8e7adbfb54f5072e50777569", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "1. Motor neurons \n\nM1\n\nM2L/R\n\nM3L/R\n\nM4\n\nM5\n\n2. Interneurons\n\nI1L/R\n\nI2L/R\n\nI3\n\nI4\n\nI5\n\nI6\n\n2. Other neurons\n\nMI\n\nNSML/R\n\nMCL/R", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 127, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "754ace57-303d-433e-a986-556843d40a34": {"__data__": {"id_": "754ace57-303d-433e-a986-556843d40a34", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 11) List of Pharyngeal Cells](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7b9e9852-65b6-4b7c-9659-dc4a98b45e04", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 11) List of Pharyngeal Cells](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "1d62f454ae94c64edd25882b17faf17c2c14e0c026aeb2a946c8130f43dc41d1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "vi. Pharyngeal glands (g)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 25, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1a6d5a49-ffb2-477e-baf9-e10975f7c7c7": {"__data__": {"id_": "1a6d5a49-ffb2-477e-baf9-e10975f7c7c7", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 11) List of Pharyngeal Cells](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3fc3af96-952d-4baf-b17e-5a84dcd38903", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 11) List of Pharyngeal Cells](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "a930d5c5364dae8bded215ea41a370632f1a195085c679434501c1bb2e2a98cd", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "1. First pharyngeal gland ring\n\ng1AL; ventral left g1 gland cell\n\ng1AR; ventral right g1 gland cell\n\ng1P; dorsal gland cell\n\n2. Second pharyngeal gland ring\n\ng2L\n\ng2R", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 166, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "75b046a6-250c-4dda-bf34-2f9343003e22": {"__data__": {"id_": "75b046a6-250c-4dda-bf34-2f9343003e22", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 11) List of Pharyngeal Cells](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1d903dde-bc74-485d-a549-c97b76191d1d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 11) List of Pharyngeal Cells](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "c09af3362d3223a4d915fa9dda3eea052bf836c59468adc2c6bd7aedf30f8ffa", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "See also PharynxAtlas", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 21, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a56374e5-b0fa-4177-9a5d-4c557dabc60b": {"__data__": {"id_": "a56374e5-b0fa-4177-9a5d-4c557dabc60b", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 12) References](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2c6eda08-fcc9-458c-b2ec-d27a89a41446", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 12) References](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "c5251e88674dc8fccda72b8d50f87a1b9dddab1640df2502a99e1fd145934dfe", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "This chapter should be cited as: Schroeder, N.E., Altun, Z.F. and Hall, D.H. 2024. Alimentary System, Pharynx. In WormAtlas. \u00a0doi:10.3908/wormatlas.1.3", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 151, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "30e5de8d-c828-4935-bc41-0fb4a1b9182b": {"__data__": {"id_": "30e5de8d-c828-4935-bc41-0fb4a1b9182b", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 12) References](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4dcf65d8-4812-4df9-8f1e-2c5c47bb102b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Pharynx, Section 12) References](https://www.wormatlas.org/hermaphrodite/pharynx/Phaframeset.html)"}, "hash": "0164cf21c647ad9c7d07d606d9f43dc1ae5db59a3129f3b82e8d456369583ee0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We would like to thank Christopher Fang-Yen for providing feedback on this chapter.\n\n Edited for the web by Nathan E. Schroeder and Laura A. Herndon. Last revision: November 7th, 2024.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 184, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f4a100e1-af4d-4cfc-bd65-56017470a9f8": {"__data__": {"id_": "f4a100e1-af4d-4cfc-bd65-56017470a9f8", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 1) Introduction](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6c2e63b4-60c8-4d52-ad00-5f87409bcd74", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 1) Introduction](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "08992b3c81a9c99ebbcdc2515c1f2f2d111576eb5eeb0e3003317a73d6371177", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The gap junctions (electrical synapses) of C. elegans constitute a ubiquitous type of cell-cell contact formed by innexin proteins. The innexins are expressed in almost every cell and while they bear no specific sequence homologies to vertebrate connexins, they form intercellular membrane channels with similarities in structure and function to those in vertebrate tissues. There is distant homology between the innexin genes of C. elegans and the pannexin protein channels of vertebrates (Phelan and Starich, 2001; Baranova et al., 2004; Penuela et al., 2013). Caenorhabditis elegans utilizes gap junctions in different ways in virtually all of its cells (see reviews by: Liu et al., 2006; Bao et al., 2007; Norman and Villu Maricq, 2007; Altun et al., 2009; Simonsen et al., 2014). Here we present molecular information and developmental aspects of gap junction formation and additionally show how gap junctions function in the adult tissues, particularly within the nervous system and motor system. The use of multiple different subunits per channel make the nematodes utilization of gap junctions more sophisticated and complex than what is currently known for vertebrate systems. Physiological studies of nematode gap junctions have mostly been done prior to any knowledge of their complex subunit usage (Stretton et al., 1978; del Castillo et al, 1989), and beg to be redone with consideration of this variable (White, 2003; Liu et al., 2013; Starich et al., 2014). There is still much more to be learned about how these same channel proteins might be utilized in hemichannels rather than as intercellular junctions.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1623, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "96e42a4c-8a79-4593-a8c3-ce85f7f1694b": {"__data__": {"id_": "96e42a4c-8a79-4593-a8c3-ce85f7f1694b", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 1) Introduction](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4825e7d8-df65-4407-963d-73da4f1933f4", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 1) Introduction](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "3792ed280f6466b74f83014271c7e35d1a27836692a40434843f262dcc05a5fe", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The following chapter combines the content of two recent reviews on gap junctions (Hall, 2016 and Hall, 2017).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 110, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a406af5d-59c7-4a05-a020-c4d0d8be82b3": {"__data__": {"id_": "a406af5d-59c7-4a05-a020-c4d0d8be82b3", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 2) Expression and Structure](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8b418e3d-b326-494c-bb56-8dfc4556dd2c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 2) Expression and Structure](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "190909241965295ca9f2fde4dd1fc23dc60de7c0f512fb94f2b4c63f2a6c41de", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Innexin genes in C. elegans show a similar diversity in number and organization to the connexin family in vertebrates, and are surprisingly numerous compared to some other invertebrates such as the fruit fly Drosophila or the planarian Dugesia. The C. elegans genome encodes 25 innexin genes, and virtually every cell type in the animal appears to express at least one innexin protein, often expressing multiple different innexin genes per cell (Altun et al., 2009). The multiplicity of innexin expression underlies the formation of heterotypic and heteromeric gap junctions, perhaps several types per cell (Liu et al., 2013; Starich et al., 2014). Heterotypic channels offer unique opportunities for developmental modulation of channel properties in a manner parallel to what is becoming well known for other forms of intercellular membrane channels, such as glutamate or NMDA receptors (Liu and Zukin, 2007; Rodenas-Ruano et al., 2012).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 938, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3157db2e-56c0-44b1-b156-798f588c2bcc": {"__data__": {"id_": "3157db2e-56c0-44b1-b156-798f588c2bcc", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 2) Expression and Structure](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a5d28440-f518-48d5-bb1e-a78ed48200d5", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 2) Expression and Structure](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "11400d3de57b251314f854761ccabd9f592a8ebd14c64788a5fa1fb5fb1303b8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Although gap junctions can appear essentially equivalent even at the ultrastructural level using standard electron microscopy (TEM) in thin sections, the junctions of invertebrate tissues stand apart from those in vertebrates when investigated by the freeze fracture (FF) technique (Staehelin, 1974; Lane et al., 1977). Vertebrate gap junction channels appear to be grouped into well-ordered clusters of intramembrane particles (IMPs), with six-fold symmetry reflecting their internal composition of six subunits per hemichannel. Invertebrate gap junctions often show larger IMPS and some may utilize more subunits per hemichannel (GapjunctFIG 1A). INX-6 channels in the C. elegans intestine involve 8 subunits per hemichannel rather than 6, forming larger IMPs and probably a wider channel pore size (Oshima et al., 2013, 2016) (GapjunctFIG 1B). Oshima et al. (2016) argue that since many invertebrate gap junctions feature relatively large IMPs when viewed by FF, this 8-fold arrangement may be commonplace for innexin-based channels.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1036, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1f887ba6-a2b6-4117-af3d-f0892af9a8e8": {"__data__": {"id_": "1f887ba6-a2b6-4117-af3d-f0892af9a8e8", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 2) Expression and Structure](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a8572dd4-8694-4c4e-82a3-407056e3b222", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 2) Expression and Structure](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "42d565afaa4c25d232a3863f39311aa165144c0b4f6520b7457f04724e1370be", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Vertebrate gap junctions always consist of IMPs cleaving to the 'P-face' of the plasma membrane replica, with corresponding 'E-face' pits seen in a matching pattern to the IMPs. However, invertebrate gap junctions often consist of mixtures of particles and pits in both replica faces, sometimes with most IMPs cleaving to the E-face (Lane et al., 1977) (GapjunctFIG 2A&B). The planarian Dugesia was the first invertebrate where it became clear that individual tissues could show unique patterns in this E-face/P-face distribution when compared by FF (Quick and Johnson, 1977).\u00a0 Early FF results in C. elegans revealed a similar diversity (Hall, 1987). Although the IMPs in many nematode tissues appear to show similar diameters and similar packing densities, the ratio of E-face to P-face particles is tissue specific and the number of IMPs per array varies widely (GapjunctTABLE 1).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 883, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d4f6640d-69ec-4b49-afb9-85c97ec1f3ae": {"__data__": {"id_": "d4f6640d-69ec-4b49-afb9-85c97ec1f3ae", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 2) Expression and Structure](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1c67b9ef-b917-4751-b020-17a28e8f051d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 2) Expression and Structure](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "f85ea902edf33dd4c10a8387bd3d769809f1287c0c4126fd8637f03e4aa479b4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Given the small size of nematode cells, most IMP arrays are necessarily relatively small. Some classes of gap junctions in C. elegans are so small in size that they can only be revealed by the FF technique, but are never large enough to be seen in TEM by thin section (Starich et al., 2014). The small size of neuronal gap junctions in C. elegans has been a major concern in trying to describe the full connectome of the nematode nervous system (Hall, 1977; White et al., 1986; Hall and Russell, 1991; Jarrell et al., 2012). Another high resolution method for discovering these arrays of IMPs uses infiltration by lanthanum salts (GapjunctFIG 2C,D). Lanthanum infiltration permits one to see the arrays of channels by negative staining, where electron dense lanthanum penetrates the narrow space between opposing plasma membranes at a gap junction, but is excluded by the channels themselves, as those channel subunits project all the way across that intercellular space (Revel and Karnovsky, 1967).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 999, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0ca18383-fb4a-4ab3-98ed-9a76dac9f256": {"__data__": {"id_": "0ca18383-fb4a-4ab3-98ed-9a76dac9f256", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 2) Expression and Structure](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "57840afb-ad31-4c4d-94cd-723bff74908e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 2) Expression and Structure](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "d66efcfa1124a672e7a4ac11ab4f5fe170d5b788de0a19cad705bfb79f0f160c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Careful anatomical studies of the entire adult of both sexes have revealed that gap junctions can be seen in virtually all tissue types, and in almost every cell in C. elegans (Hall and Altun, 2008). In some larval tissues, gap junctions are seen early in development, only to disappear when groups of epithelial cells fuse to form larger syncytia in the adult (Nguyen et al., 1999). Large gap junctions can allow transfer of fluid, ions or small molecules between dissimilar cell, as in the excretory system (Hall, 2016; Hall and Altun, 2008). When viewed globally across C. elegans tissues, the pattern of innexin expression across neighboring cells suggests that heteromeric and heterotypic gap junction channels will be common in C. elegans (Altun et al, 2009).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 765, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a9246b45-cdea-4d36-857b-085d5361acd6": {"__data__": {"id_": "a9246b45-cdea-4d36-857b-085d5361acd6", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 2) Expression and Structure](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d3de9c5b-ec51-47e0-8f29-f2ae20c9271d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 2) Expression and Structure](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "ff29a67ccb145dea591511c307f8a8fd5186edba691440782b7fb122de378f1a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The amino acid sequences of the innexins of C. elegans (and other invertebrates) do not resemble the sequences of gap junction proteins of vertebrates, known as 'connexins'. However they do share overall similarity with the 'pannexins' of the vertebrate world (Baranova et al., 2003). The human genome includes 3 different pannexin genes, none of which seems to form true gap junctions (Chiu et al, 2014; Retamal and Saez, 2014). However, pannexins have been implicated in acting as membrane ion channels that do not link to similar channels in an opposing membrane, but instead act as 'hemichannels' (Bruzzone et al, 2003; Sosinsky et al, 2011; Retamal and Saez, 2014). Such hemichannels are proving important in a variety of human diseases, including inflammation, ischemia and tumor genesis (Chiu et al, 2014).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 813, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "40f74a64-3687-4489-9642-9f0a342fc45f": {"__data__": {"id_": "40f74a64-3687-4489-9642-9f0a342fc45f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 2) Expression and Structure](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "991e9013-83f1-4cbe-ac6f-e338d8d682bc", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 2) Expression and Structure](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "21ce42e3abc11d7452d7e66f0c0373b0cf8552a3b57e95a9b4171a27dd9ffa6a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Hemichannels in vertebrates can sometimes function as stretch receptors (Richter et al., 2014). The nematode innexin unc-7 can also act as a hemichannel in several different sensory neurons, including the touch cells (ALM, PLM, etc) and in the harsh touch cells (PVD), and in both instances the unc-7 hemichannel acts as a receptor either for gentle touch, harsh touch, or both (Walker and Schafer, 2020). An earlier report by Bouhours et al (2011) had previously demonstrated that unc-7 may also act as a hemichannel at neuromuscular junctions in C. elegans. Remarkably, when the human pannexin 1 sequence is used to replace UNC-7 protein in the touch neurons of an mutant, pannexin1 hemichannels can rescue touch sensitivity in ALM and PLM (Walker and Schafer, 2020).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 769, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "64c5921b-fa5c-4926-ba0e-fc6939b41b2a": {"__data__": {"id_": "64c5921b-fa5c-4926-ba0e-fc6939b41b2a", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 3) Development](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1320d985-d977-4bb5-b196-94bc9618c907", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 3) Development](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "0123fa797fd3d7c3dcfb94e8c76fec6c7fff1e60b45c2edfd7cabf52ab9a60f7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The roles that gap junctions play in tissue development may be diverse, but few innexin mutants have proven to be lethal, although some alleles do produce low levels of dead embryos. For instance, inx-3 mutant alleles yield occasional dead embryos in which the pharynx becomes detached from the intestine, apparently due to the weakening of tissue linkages at the pharyngeal valve (Starich et al., 2003). Indeed, INX-3 protein is expressed everywhere in the early embryo, and can be detected in small plaques ubiquitously even before the embryo begins gastrulation. It appears that at this early stage, all cells may be communicating with neighbors via gap junctions, at or near the time when these cells are undergoing 'global cell sorting' to migrate from the place of their birth to form functional groupings before tissues begin to form (Bischoff and Schnabel, 2006). Sister cells often have different fates, and some individual cells always undergo apoptosis. For development to progress, many cells must separate from their sisters after cell division and migrate to locate their proper partners before tissue morphogenesis can begin. Although unproven, it seems reasonable that gap junctions may play an accessory role in intercellular communication among undifferentiated cells to foster cell sorting, or to enhance cell clustering at the outset of morphogenesis. Stronger coupling might then help to synchronize or coordinate the morphogenesis within cell groups. Alternately, gap junctions may play an adhesive role during cell motility at this early stage in embryogenesis.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1584, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1d76dafc-c9e2-4eca-96ed-8d7e5cccb445": {"__data__": {"id_": "1d76dafc-c9e2-4eca-96ed-8d7e5cccb445", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 3) Development](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6f03a74f-2cbd-42a7-93b3-ec70ccdf51f8", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 3) Development](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "d3f884779ac39d54ab63896f13fb55ddedda104a4e432f14686acbe0b07fdb8f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Coincident with the early wave of INX-3 expression, INX-8 and INX-9 expression in the early embryo is associated with proper maturation of the eggshell (Starich et al., 2014; Stein and Golden, 2015). Mutations in either gene lead to leaky eggshells that permit diffusion of DAPI into the early embryo, with defects noted as early as the 4-cell stage. Other early defects in these mutants include failures in cytokinesis during early cell divisions, and the extrusion of polar bodies just beneath the eggshell.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 509, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "43d22230-2f98-49fb-afaf-5ff5c5d339a3": {"__data__": {"id_": "43d22230-2f98-49fb-afaf-5ff5c5d339a3", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 3) Development](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0bbcf06c-3151-480b-bc2b-38c624b3e113", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 3) Development](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "7e16c01399e4252955372bf3a04804eb53fe9d426b9a1383b23a7b6d2565e7c6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "As tissue development proceeds, virtually all cell types express one or more innexins, and gap junctions have been detected anatomically at the borders of most epithelial cells where they contact their neighbors within an epithelium (GapjunctFIG 3). As the early embryonic pharynx defect in inx-3 mutants suggests, gap junctions may also play a structural role in tissue integrity by linking one tissue to its neighbor, although adherens junctions are also widely utilized in the same role (Koeppen et al., 2001). GapjunctFIG 3C shows an example from the adult pharynx where an adherens junction and a gap junction lie side by side to help in attaching muscle and support cells tightly together. The nematode body plan involves many syncytial epithelia, and gap junctions have been seen by TEM along cell borders in advance of targeted cell fusions (including self-fusions) both in the embryonic excretory system (Stone et al., 2009; Abdus-Saboor et al., 2011; Mancuso et al., 2012), and in hypodermal cells in the late larval male tail (Nguyen et al., 1999). Thus, communication across gap junctions may help to guide certain steps in tissue morphogenesis.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1157, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ec2a0ff9-655e-4e05-b594-5d9c48d79b3b": {"__data__": {"id_": "ec2a0ff9-655e-4e05-b594-5d9c48d79b3b", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 3) Development](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "dc44afa9-1316-47e4-af4c-06a618798e14", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 3) Development](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "72aae1af9e9d0b505ee2ed74603ca789d3915073fd491449238945d64016d9be", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Transitory gap junctions have been shown to occur between developing neurons at a time when they are choosing between alternate cell fates (Chuang et al., 2007).\u00a0 The innexin gene nsy-5 is expressed in a cluster of neuron cell bodies in the lateral ganglion during late embryogenesis and early L1 stage, perhaps 12 neurons per side. Mutations in nsy-5 cause errors in the specification of the AWC neurons (AWCL and AWCR), where generally one cell chooses the AWC-ON cell fate while the opposite cell adopts an AWC-OFF fate. Gap junctions encoded by the nsy-5 innexin actually link multiple neurons in each lateral ganglion, including AWC, ASH and AFD during embryogenesis, but the AWC fate choice is the best described event requiring these intercellular junctions. After the L1 stage, the expression of NSY-5 protein diminishes and protein expression is not known to persist into later larval stages except in a few lateral neurons, including ASH, but not AWC (Chuang et al., 2007). Indeed, the reconstructions of adult lateral ganglia (White et al., 1986) failed to note any gap junctions among these neuronal cell bodies, but TEM studies of the late embryo did find gap junctions linking ASH to AWC, and AFD to ASH on each side (Chuang et al., 2007). Indeed, TEM evidence for these junctions was not found even in the L1 larval stage, suggesting that their role in cell fate choice has been accomplished during late embryogenesis.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1433, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "626537cf-9ea4-4ed2-8261-4dfa1a177761": {"__data__": {"id_": "626537cf-9ea4-4ed2-8261-4dfa1a177761", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.1) Muscle](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "faf49d75-6630-4c7b-ad5f-359a9274444d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.1) Muscle](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "d296fb75769cf52819eaa90f2ad13008900a6445438782b7c1e2ea1b2838f249", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "There are a handful of major groups of muscles in the animal, and within each grouping, gap junctions prominently link homologous (or related) muscles to their immediate neighbors (GapjunctFIG 3 and GapjunctFIG 4). This underlies coordinated contractions passing along the length of various body structures during normal behavior, or which operate during more complex sequential events, such as pharyngeal contractions during food consumption, egg-laying by the hermaphrodite, defecation by specialized tail muscles, and the male tail's discrete sequence of mating behaviors involving many different muscle groups. (For overview see Hermaphrodite Muscle System - Introduction.)\n\n GapjunctFIG 4: Gap junctions link muscle cells into functional units. A. Pharyngeal muscles fall into 8 segmental sets, pm1-pm8, with gap junctions ( red symbols ) linking neighboring segments to one another. Additional gap junctions link all muscles within a segment indirectly for pm2-pm7, via local gap junctions to marginal cells (not shown). Waves of radial contractions pass quickly along the pharynx, even without chemical synaptic input, causing widening of the central lumen. Each segment has been pulled slightly apart graphically to show where gap junctions link them to neighboring segments. Anterior is to the left in each panel. B. Head and bodywall muscles are arranged in almost segmental fashion, with gap junctions connecting all neighboring muscles, both in L/R groups, and linearly along the head and bodywall. Most gap junctions occur on extended muscle arms, as highlighted in panel C . Waves of contraction pass along the body, causing local shortening of either dorsal or ventral muscles, while the opposing quadrants relax in the same locale. View from left aspect at low power, showing only the left side BWM quadrants; compare to panel C showing all four BWM quadrants. C. Bodywall muscles (BWMs) contact neighbors via specialized long thin muscle arms extending medially, where they exchange gap junctions with other muscles, and receive neuromuscular junctions from motor axons lying in the two motor nerve cords (shown in red). White circles mark locales where neuromuscular junctions and gap junctions occur at dorsal and ventral muscle plates. D. Three types of specialized (non-equivalent) muscles for defecation in hermaphrodite tail extend muscle arms to the surface of pre-anal ganglion (shown in pale red). White dotted circle indicates zone where overlapping muscle arms form gap junctions with one another, and receive neuromuscular junctions from motor axons.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2579, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "21a93d45-1a12-4335-8341-5bedb7b88407": {"__data__": {"id_": "21a93d45-1a12-4335-8341-5bedb7b88407", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.1) Muscle](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8ceffbf8-1d4a-42ce-82a9-122586b9807b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.1) Muscle](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "1ccc8f1386c6ddaea60a128b23e07008161c27709389b30bb596a8da739b1795", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The pharynx is responsible for the ingestion and preliminary processing of its main food source, small bacteria, by very rapid contractions of coordinated muscle groups that are well connected by gap junctions (see Hermaphrodite Alimentary System - Pharynx). Pharyngeal muscle groups lie in eight consecutive segments along the alimentary canal (GapjunctFIG 4A and GapjunctFIG 5). Muscles are linked within each set to all the other muscles in their segment via gap junctions to marginal cells (which separate muscles within each segment) (GapjunctFIG 3), and then linked again to muscles in the adjacent segment along the chain (Albertson and Thomson, 1976; Altun et al., 2009). These pharyngeal gap junctions underlie extremely fast radial contractions during feeding to sweep food items along the alimentary canal (Trojanowski et al., 2016). Virtually all pharyngeal muscle groups are organized in segmental fashion, and connected to their neighboring segments, including support cells, by a multiplicity of innexin channels (GapjunctFIG 5). Pharyngeal contractions are too rapid to be explained by chemical synaptic inputs from motor neurons, although pharyngeal neurons may influence the pharynx to change from one mode of action to the next (Raizen and Avery, 1994; Trojanowski and Fang-Yen, 2015). Instead, spontaneous contractility of the individual muscle types must drive the rate of action. It has been shown that virtually all pharyngeal neurons can be laser-ablated, individually or en masse, without abolishing the basal rhythm of muscle contraction (Avery and Horvitz, 1989). Pharyngeal muscles are divided into eight small groups of cells along the length of the organ (GapjunctFIG 3). Within one cell group (segment), all muscles appear to express the same set of innexins, and in virtually all cases they express several innexins either at high levels or at lower levels (Altun et al., 2009). Along the length of the pharynx, neighboring segmental groups express different assortments of innexins, so that heteromeric gap junctions between segments seem likely to be the rule here rather than the exception (GapjunctFIG 5).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2141, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9cd0d9de-145b-45b1-8bc7-514311af3b58": {"__data__": {"id_": "9cd0d9de-145b-45b1-8bc7-514311af3b58", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.1) Muscle](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bcadcce2-1096-4c38-a36f-fb97817e35f9", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.1) Muscle](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "a6361547464a83e91c68b337536cd5009abfaa456ccfae73a6be3b93a5c5166d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In the bodywall muscles along the length of the animal, 95 muscles are grouped into four quadrants, with a double row of muscles lying within each quadrant, effectively creating 12 segments along the main body axis (Hall and Altun, 2008; Hermaphrodite Muscle System - Somatic Muscle). Spindle-shaped bodywall muscles extend sarcomeres along the bodywall, and also form unique thin extensions called 'muscle arms' to reach medially towards the 'muscle plate' (GapjunctFIG 4B&C) (White et al., 1976). These body muscles all express at least 6 innexins per cell, generally including the same set in all muscles for any stage in development (Liu et al., 2013). The cells are electrically coupled by gap junctions that are restricted to 'muscle arms' that extend from each cell towards either the dorsal or ventral motor nerve cord. Here each muscle arm is contacted by neuromuscular junctions (NMJs) from several categories of principal motor neurons (White et al., 1976; Liu et al., 2006; Hall and Altun, 2008). Where present, muscle arms also form prominent sets of gap junctions among themselves. Thus each muscle is linked to all its nearest neighbors on the dorsal side (or on the ventral side), including left/right dorsal or ventral pairings, but never reaching across the divide between dorsal and ventral quadrants (GapjunctFIG 4B&C). These gap junctions at muscle arms also link muscles 'segmentally' along the body to its anterior and posterior nearest neighbors.\u00a0 As a result, muscles lying with each muscle quadrant can conduct action potentials from head to tail or vice versa, depending on local activities that initiate a contractile wave in either the tail or the head to be passed along the body (White et al., 1976; Hall and Altun, 2008; Liu et al., 2006; Liu et al., 2011).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1789, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2a64e448-04d7-4158-958d-7720bec19732": {"__data__": {"id_": "2a64e448-04d7-4158-958d-7720bec19732", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.1) Muscle](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a6bacb25-c9ae-4721-b1e0-8e1648d5987c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.1) Muscle](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "99d64fabcad1e2c899de4186491027f16311a0cd9405aa640475de4abdd9119c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Although the gap junctions along the major nerve cords represent the principal means to couple muscles in the four quadrants, there are additional gap junctions found between close neighbors within each muscle quadrant, both among the head muscles (GapjunctFIG 6B) and among bodywall muscles of the rest of the body (White et al., 1986; Qadota et al., 2017). These additional junctions occur on lateral cell membranes amidst the sarcomere regions. They cannot link L/R pairs, nor dorsal/ventral pairs, but only close neighbors within a row within one\u00a0 quadrant. Their relative importance in control of muscle contractions is not understood.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 640, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6e479a2c-65a7-4bb3-9bf4-c91e62b15efc": {"__data__": {"id_": "6e479a2c-65a7-4bb3-9bf4-c91e62b15efc", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.1) Muscle](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2dc4acae-49f1-46bf-b307-56a9a924e684", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.1) Muscle](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "f03604b98cd554667bac275510eefe7f597f64498bcd7307f1f372dc2b705732", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The layout of neuromuscular junction inputs to all bodywall muscle cells within a 'segment' should insure that all nearby cells on the ventral side (i.e. both ventral quadrants) of the body will act in synchrony, and antiphasic to all muscle cells within the corresponding segment on the dorsal side. The neuromuscular junctions from a fascicle of motor axons are grouped near muscle arm branches in a manner at each motor nerve's 'muscle plate' where all muscles within the ventral segment may receive some fractional share of each quantal release of neurotransmitter at the muscle plate (Liu et al., 2006), and similar sharing of transmitter release occurs at the dorsal muscle plate for all dorsal bodywall muscles. While these multiplex neuromuscular junctions should help to keep all muscles in synchrony locally, there is perhaps a stronger input via electrical signaling among the converging muscle arms themselves. Moreover, since each muscle cell tends to have arms extending from the extreme ends of the full cell length, and because there is some overlap at these endpoints to muscles of the next 'segment', electrical signals should rapidly conduct within a quadrant from muscle to muscle along the length of the body to modulate contractility of the whole animal and its body shape. Genetic knockdown of any of six different innexin genes can partially inhibit this coupling, but there is no single innexin knockout that can fully extinguish coupling, as measured by intracellular recordings in a partially dissected preparation (Liu et al., 2013). Among these six innexins, the patterns of physiological deficits judged from such recordings suggest that there may be two different classes of heteromeric gap junctions here, one class involving two different innexins, and the second class involving four other innexins (GapjunctFIG 1B). \n\n 4.1.3 Head Muscles", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1872, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c0121e52-0619-4faa-81a4-41ebb38c6d1a": {"__data__": {"id_": "c0121e52-0619-4faa-81a4-41ebb38c6d1a", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.1) Muscle](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3f786619-3023-454f-884a-d29e9d71f982", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.1) Muscle](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "23149574488bb89232999e411192d3849edf4c5647913f5d9798dc8aad8453a0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Head muscles use gap junctions to link all muscle cells in each of the four quadrants to one another within the quadrant, and via muscle arms extending near the anterior pharynx, contacting other muscle quadrants and the GLR support cells along the inner surface of the nerve ring (GapjunctFIG 6; Hermaphrodite Muscle System - GLR cells). GLRs are linked via gap junctions to each other, and also to a set of four RME motor neurons from the nerve ring. Importantly, the four muscle quadrants in the head can still operate somewhat independently from one another, so that the animal can control head motions in all directions, unlike the restricted range of motion possible for other bodywall muscles.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 700, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4b481bb5-3647-4cd7-875e-55af84274e56": {"__data__": {"id_": "4b481bb5-3647-4cd7-875e-55af84274e56", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.1) Muscle](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0582fdbb-59ad-4b20-bcc5-2bb909b6c3c5", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.1) Muscle](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "1ea5b23e71a4c316277484ae1125a477c309d49798778bda574d5045b21f4202", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "GapjunctFIG 6: Muscle arms of the head muscles are linked by gap junctions. A. Diagram showing two stylized head muscle arms ( dark green ) approaching nerve ring. Muscle arms from the 32 muscles in the head and neck project onto the inside surface of the nerve ring in a highly ordered fashion. Their terminal branches lie between the processes of GLR cells ( golden yellow ) on the inside and the motor neurons of the nerve ring ( dark red \u00a0and\u00a0 purple ) on the outside. Arms from the somatic head muscles run posteriorly until they reach the posterior nerve ring region. The arms from each muscle row then make an anterior arc of about 45' and extend inward to reach between the outside surface of the GLRs and the inner surface of the neural plate. This inward turn involves close apposition to the GLR cell bodies. In the neck, somatic muscles extend arms both to the nerve ring and to either the ventral or dorsal nerve cords where they receive additional synapses (not shown). ( Light green ) pharynx; ( orange ) basal lamina.\u00a0 B. GLR cells make extensive gap junctions ( red bars ) to the muscle arms and to RME neurons as shown. For stylistic reasons, RME  processes are shown inside the GLR cell layer. In actuality, they lie outside the GLRs and muscle plate. There are also gap junctions between RME  neurons and between the muscle bellies of the muscles, occurring on lateral cell membranes where two muscles meet within the quadrant. No gap junctions are seen between the muscle arms of cells within the same quadrant, but gap junctions exist between arms of cells in different quadrants. (Based on\u00a0 White et al., 1986 .)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1635, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "09c9cb46-dd4c-4099-ab08-c8fd3f0d81f8": {"__data__": {"id_": "09c9cb46-dd4c-4099-ab08-c8fd3f0d81f8", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.1) Muscle](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f9023b80-7051-4175-b8f6-54866dff0678", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.1) Muscle](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "e8c09ea179fe5136cef0fcff727ecc547836c8069a53c7b4248ba8de9f4abcd9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "4.1.4 Sex-specific Muscles\n\n4.1.4.1 Gonad Sheath and Spermatheca", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 64, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0983604b-714e-421a-8021-627d71ea996b": {"__data__": {"id_": "0983604b-714e-421a-8021-627d71ea996b", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.1) Muscle](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9bb77fb9-cd74-472e-91ab-f67ae4e0f5bf", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.1) Muscle](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "f29f1d3793fdcb186ba698e0f33f5603102f379066b12256372040736b92f67f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Contractile elements of the somatic gonad (known as the gonad sheath) (see Hermaphrodite Reproductive System - Somatic Gonad) squeeze on the germline to force this tissue into a cylindrical shape. Somatic sheath cells are connected by gap junctions to their left/right homologues, and segmentally to other sheath cells along the length of the gonad (cf. SomaticFIG 6D) (Hall et al., 1999). Progressive waves of contraction by the sheath are thought to help push germ cells proximally, towards the spermatheca. The somatic sheath cells closest to the spermatheca also form large (transient) gap junctions to the primary oocyte, in the region closest to where the oocyte will be fertilized (cf. SomaticFIG 6C). The larger gap junctions connecting sheath cell 5 to the primary oocyte coordinate internal activities within the oocyte (seen as swirling motions by light microscopy). Rhythmic squeezing by sheath cell 5 forces the primary oocyte towards the spermatheca when it is ready for fertilization (Hall et al., 1999).\u00a0 Separately, sheath cells and the distal tip cell are each linked by hundreds of tiny gap junctions to the underlying germ cells (Starich et al., 2014). The smaller gap junctions between somatic gonad cells and developing germ cells help govern germ cell maturation (Starich et al., 2014). Gap junctions between all cells of the spermatheca help these cells to contract radially in unison to allow entry of the primary oocyte (cf. SomaticFIG 9EF) (Hall and Altun, 2008). But there are no synaptic connections between the nervous system and these muscular elements of the ovary.\n\n4.1.4.2 Vulva, Uterus and Male Sex Muscles", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1641, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "57317ee9-b689-46b6-9160-1bba4825afb1": {"__data__": {"id_": "57317ee9-b689-46b6-9160-1bba4825afb1", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.1) Muscle](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5f97c0ba-04ae-4cfa-b9d6-ff3384ad36de", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.1) Muscle](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "feba710c3d82c8edd54abafbe80876bf0bd1293fcfe378f43f3781f21584c384", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sex-specific muscles of the hermaphrodite vulva and uterus are heavily linked by gap junctions, as are the specialized sex-specific muscles of the male tail (White et al., 1986; Sulston et al, 1980; Jarrell et al., 2012) (see Hermaphrodite Reproductive System - Egg-laying Apparatus and Male Muscle System - Male Specific Muscles). Thus, homologous muscles can operate coordinately, and related muscle groups can act sequentially, in quick succession. Some of these contractions can be vigorous and rapid, synchronized via gap junctions, acting much faster than ongoing neuronal patterns. A limited set of neuromuscular junctions link the hermaphrodite nervous system to a few members of the vulval muscles, and indirectly influence the uterine muscles via muscle-muscle gap junctions (cf. EggFIG 13) (White et al., 1986). Chemical neuromuscular junctions to the male tail's sex muscles are more elaborate, but gap junctions are extensive among all these sex muscles (cf. MaleMusFIG 30, 31 & 32).\n\n4.1.4.3 Defecation Muscles", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1024, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d1f13cf2-e992-4d8e-81c2-2a1054edfc0a": {"__data__": {"id_": "d1f13cf2-e992-4d8e-81c2-2a1054edfc0a", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.1) Muscle](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b0a707eb-7324-4872-b905-7e0bea49cb1a", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.1) Muscle](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "5d0596ebacc43de99279cea3ee159306d5de031339f4f1fccf1dd381dc8e0da1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Defecation muscles in the tail operate in coordinated fashion to open the rectal valve and inflate the rectum during defecation (see Hermaphrodite Alimentary System - Rectum and Anus and Male Alimentary System - Defecation Muscles). These actions are governed by several non-equivalent muscles, linked by muscle arm extensions to form gap junctions among themselves in the same zone where they receive neuromuscular junctions from a single motor axon (DVB) (Hall and Altun, 2008) (GapjunctFIG 4D).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 497, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d772f8a3-9d92-41db-9e32-af5372753a38": {"__data__": {"id_": "d772f8a3-9d92-41db-9e32-af5372753a38", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.1) Muscle](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "31f015ea-706d-4805-befd-5ab70856ee4a", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.1) Muscle](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "c3c70dae3255b81efd4c73ed3b96a1bfbfbf63fb6b9fb736c5834611dc390c17", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "4.2 Somatic Gonad and Germline", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 30, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0ba4ea19-7564-4dc9-a93e-ce68f1ed1d15": {"__data__": {"id_": "0ba4ea19-7564-4dc9-a93e-ce68f1ed1d15", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.2) Somatic Gonad and Germline](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9d0dfd31-afc8-41b0-856c-4e03b6a35435", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.2) Somatic Gonad and Germline](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "304ed8cf118249c429fa617311eaf43cd7fe90ffc9d0b972b6171d667fc78534", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Complex expression patterns for multiple innexins have been seen in small gap junctions between germline and somatic gonad, with several important developmental consequences. The somatic sheath cells and distal tip cell create a niche environment required for the development of the germline (Hall et al., 1999; Byrd et al., 2014; Starich et al., 2014) (see Hermaphrodite Reproductive System - Somatic Gonad and Reproductive System - Germline). Although larger gap junctions have been found between germline and soma in the proximal arm of the gonad (Hall et al., 1999), a new class of very small gap junctions has been discovered in the distal arm using freeze fracture (FF) and antibody staining. In the distal gonad arm, all individual junctions are too tiny to be discerned by standard TEM in thin sections (Starich et al., 2014). Some of these junctions connect the distal tip cell to the dividing germ cells at the distal end of the gonad arm, while similar small junctions connect the somatic sheath cells to the developing germline closer to the bend in the gonad arm (aka the 'reflex'). These gap junctions individually are composed of very small numbers of channels (IMPs per array seen by FF), but are collectively numerous where they connect germ cells to the overlying somatic gonad. Genetic knockdown of any one of five innexin genes leads to systematic defects in germ cell maturation, and the evidence suggests that a typical gap junction channel consists of two different innexin proteins in one hemichannel (on the germline side) and a different pair of innexin proteins in the opposite hemichannel (on the gonad sheath side) (GapjunctFIG 1D). The mixture of innexin usage differs gradually along the length of the gonad arm, so that a fifth innexin gradually substitutes at hemichannels at the opposite end of the extended chain of sheath cells. Communication via innexin channels here is necessary for the germline cells to switch from mitosis to meiosis as they move along within the gonad arm. Interestingly, since these individual germ cells each slowly move relative to the overlying gonad sheath, they must break and reform gap junctions continuously as they traverse the length of the gonad arm and around the bend towards the uterus. The same germ cells are also connected to nearby neighbors within the germline via a central syncytium, the acellular 'rachis' (Hall et al., 1999).\u00a0 This open door between all germ cells negates the chance that their gap junctions are allowing electrical signals to propagate, but to allow small molecules to be relayed between soma and germline. The dynamics of this situation are quite exciting, and much remains to be explored about how these gap junctions operate.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2729, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7e478dd8-67d7-4ec5-9c58-65fba8af25b3": {"__data__": {"id_": "7e478dd8-67d7-4ec5-9c58-65fba8af25b3", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.2) Somatic Gonad and Germline](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c3d340ea-8a7d-4173-9dc6-ae0c076821d7", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.2) Somatic Gonad and Germline](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "ba9f4b16db8dfacd77e58663c2efc1b705bc19c3378ef306e88eb884b929b5e2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "4.3 Excretory Canal Epithelia Cells", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 35, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9468d694-0309-48a6-b1a4-00a1a2f89921": {"__data__": {"id_": "9468d694-0309-48a6-b1a4-00a1a2f89921", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.3) Excretory Canal Epithelia Cells](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c6740da6-6b95-443c-b30b-e87fd46509be", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.3) Excretory Canal Epithelia Cells](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "d9ae994cbb6977335e4182386f895d10d46decfe3c511bcd12fa40ae5a8fb064", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Besides their roles in electrical signaling, gap junctions can permit the transfer of small molecules or fluid between tissues. This is well established for connexin-based junctions in vertebrates (Goldberg et al., 2004), but is not well established for many invertebrate innexin channels. The relatively large physical pore size of some innexin channels should favor passage of larger molecules and solutes (cf. Oshima et al., 2013, 2016). Although the permeability and gating of most innexin channels remains to be carefully explored, some prominent C. elegans gap junctions are already implicated in metabolic processes. For instance, the gap junctions between the excretory canal cell and the hypodermis are especially large and collectively occupy a substantial fraction of the membrane surface area where these two tissues meet (GapjunctFIG 3D) (Buechner et al., 1999; Hall and Altun, 2008). The canal cell extends lateral arms from its cell body to the far reaches of the head and tail, and operates as the kidney for C. elegans, removing excess fluid from the body and excreting this fluid through the excretory duct (see Hermaphrodite Excretory System). Deeply embedded into the surrounding hypodermis, the excretory canals collect fluids, potentially via their prominent gap junctions with the hypodermis.\u00a0 Those fluids are then filtered via the elaborate canaliculi from the canal cytoplasm into the luminal space within the extended canals, before export via the excretory duct. Mutations that disrupt the continuity of the excretory duct cause lethal consequences in the embryo and early L1 larval stage, due to a fluid buildup that swells the animal into a 'lethal rod' phenotype (Stone et al., 2009). Some mutant alleles in inx-12 and inx-13, the two main innexins expected to form the heterotypic junctions between hypodermis and the canal cell (Altun et al., 2009), also result in dead L1 larvae exhibiting lethal rod morphology (Todd Starich, pers. comm.). Although there are other possible explanations, these results suggest that INX-12/INX-13 junctions may facilitate water transport from hypodermis to canal cell.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2135, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a54b1bfe-d39b-4190-9a2f-b1d714f529c7": {"__data__": {"id_": "a54b1bfe-d39b-4190-9a2f-b1d714f529c7", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.3) Excretory Canal Epithelia Cells](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "54e6f8e8-37d8-4ae3-bfe5-a858b16c9ecc", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.3) Excretory Canal Epithelia Cells](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "ced1ffdbaca283dd2ebc5059cb00250e876feae67f2f18051527eaa645d64796", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Many classes of epithelial cells with C. elegans are also linked to their nearest neighbors via gap junctions (Hall and Altun, 2008). Depending on the cell type, these junctions may be large or small, but many can be seen easily by TEM. This is true for hypodermis, intestine, and the anterior epithelial cells of the buccal cavity and pharynx, none of which is expected to electrically excitable. In each case, it seems more likely that cells within an epithelial compartment can exchange small molecules to like cells. The small gap junctions discussed above between soma and germline in the nematode gonad also seem to involve a metabolic relationship rather than electrical signaling. In the case of the intestine, a calcium wave is seen to pass along the chain of intestinal cells via homomeric INX-16 gap junctions that help to coordinate the defecation cycle (Peters et al., 2007). Additional innexins are also expressed by the intestinal cells that still permit dye coupling even in inx-16 mutants, but INX-16 alone seems to be required for normal propagation of calcium waves (Peters et al., 2007).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1107, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8c197eec-620c-4796-9a90-8854fbe38049": {"__data__": {"id_": "8c197eec-620c-4796-9a90-8854fbe38049", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.4) Nervous System](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "613114be-9fbf-46b3-89ea-a6b54bb381bd", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.4) Nervous System](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "7821eb108eab6cd5ff2ab253c906fc6769969dea666d18a0ee61166f73b4fac2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Gap junctions within the nervous system connectome play diverse roles (see Hermaphrodite Nervous System). Sometimes they mimic connectivity patterns created by chemical synapses. But in other places, as in some muscles, gap junctions play a unique role in coupling arrays of cells, either to synchronize activities, or to provide a pathway to propagate signals independent from the chemical synapse network (Liu et al., 2011). Although there are only 302 neurons (see Individual Neurons for complete list) and 56 glia in the adult C. elegans hermaphrodite (White et al., 1986), the diversity of innexin expression within them is currently unmatched in any other model organism. Fully 20 of the 25 innexin genes have been shown to be expressed in one or more cells in the nervous system (Altun et al., 2009).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 807, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ae395ad2-3322-4e8a-912e-34702c6a4057": {"__data__": {"id_": "ae395ad2-3322-4e8a-912e-34702c6a4057", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.4) Nervous System](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "91b29ec6-b5b2-4f18-8155-4be5af63b80c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.4) Nervous System](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "d671d5b34128cc6ac8f981fa92d9bd5255a69df52416d5b1ff270faf2fc093c0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Some innexins appear to be expressed in a very restricted set of cells. INX-14 is expressed only in the GABAergic inhibitory motor neuron classes, DD and VD. INX-5 is expressed mostly in glial cells, but in very few neurons. INX-2 is expressed only in AVK, and INX-1 only in AIB and briefly in AIY neurons. However, eight innexin genes are expressed in 15-30 neuron classes each. Furthermore, some neurons express groups of different innexins at once, and a few neurons may express as many as a dozen innexin genes.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 515, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4662ef39-87f2-4165-8906-fb9a0a0e90c9": {"__data__": {"id_": "4662ef39-87f2-4165-8906-fb9a0a0e90c9", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.4) Nervous System](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "18e13b8a-e026-4a21-899c-332d1d0338b6", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.4) Nervous System](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "c71d63394a82277b6d64ec48196f9044736efa1029be207e654a5f0968f44a69", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "As virtually all of the 302 neurons are expected to form gap junctions with other neurons, the issue of heteromeric and heterotypic channels arises immediately. Early hints for innexin mixtures were suggested from genetic studies of 'uncoordinated' animals, where single mutations of different innexin genes gave rise to no obvious phenotype, or to only mild or moderate dysfunction in neurons and muscles (Starich et al., 1996). This suggests that redundancies must blunt single gene mutant phenotypes. Despite trouble in finding the smallest junctions by TEM, about 6,000 neuronal gap junctions have been identified in the hermaphrodite, and about 10,000 in the adult male (White et al., 1986; Hall and Russell; 1991; Jarrell et al., 2012; Cook et al., in prep.).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 765, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "157dd6b5-d31d-4960-8eb3-879c38b47eff": {"__data__": {"id_": "157dd6b5-d31d-4960-8eb3-879c38b47eff", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.4) Nervous System](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5667e0bd-cf44-424e-b3a0-7091eb3b872c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.4) Nervous System](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "2811c9b0bf27490a47db3924eb27bc8367f9e2829d350d30987ca518d55cc539", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In many instances within the nematode connectome, one finds that the pattern of gap junction connectivity is quite similar or parallel to the pattern of chemical synaptic contacts (White et al., 1986). However, there are certain levels in sensory processing where gap junctions tend to dominate. For instance, a 'hub-and-spoke' pattern has been suggested for the convergence of multiple head sensors to communicate via gap junctions onto a single interneuron, RMG (Macosko et al., 2009) (GapjunctFIG 8). This arrangement may facilitate coordination of several classes of sensory neuron activities, allowing the level of RMG activity to synchronize or facilitate the animal's responses to different modes of input towards a common output. In this case, RMG activity is apparently governing the animal's choice between social behavior and solitary behavior, i.e. encouraging the animal to aggregate with other nematodes. Elsewhere gap junctions ought to allow for better synchronization and faster responses in decision making since synaptic delay is minimized. \n\n 4.4.1 Synapses between layers", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1092, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3bf9ce92-80da-41c2-bc5d-7a9f6dafb347": {"__data__": {"id_": "3bf9ce92-80da-41c2-bc5d-7a9f6dafb347", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.4) Nervous System](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e2d6da69-2391-4f97-a56c-2e66f741ee9f", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.4) Nervous System](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "5abfac9f91312da627e3ec67c4d003bc8962bff1bda88c9fb4259727023a2941", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "As one inspects intercellular signals flowing from sensory cells to interneurons and then motor neurons (White et al., 1986; Hall and Russell; 1991; Jarrell et al., 2012; Faumont et al., 2012; Varshney et al., 2011), much of the general pattern is produced by chemical synapses. Output from motor neurons onto muscles (NMJs) is limited mostly to chemical signaling. Only a minority of contacts between neuron layers involves gap junctions, and their pattern of contacts is often similar to the chemical synaptic network (GapjunctFIG 7). One difference is that chemical synapses in C. elegans tend to form as dyads, where one presynaptic neuron simultaneously synapses onto 2 or more postsynaptic neurons (White et al., 1986; Hall and Russell; 1991). Gap junctions must occur as one to one cell contacts, so that a neuron seemingly cannot choose multiple gap junction partners at once. Nevertheless, gap junction partnerships operating between cell layers are often the same as principal choices for chemical synaptic partnerships. Although we still do not understand how most neurons choose those partners (Emmons, 2016; Kim and Emmons, 2017), the same intercellular mechanisms might be used to recognize suitable partners for both chemical and electrical synapses.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1265, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5f8a677c-e5c5-4dfd-a75e-54b2b270eeb9": {"__data__": {"id_": "5f8a677c-e5c5-4dfd-a75e-54b2b270eeb9", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.4) Nervous System](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2829c616-09fe-4c76-b12a-41ce4061c267", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.4) Nervous System](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "c6723b2a2c6346076c0ac6f80374254507a51760ed2617c809200baeea61e68e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The most well studied gap junctions between two neuron layers are those linking the command interneurons (or 'premotor neurons') of the ventral nerve cord to motor neurons along the same cord, controlling contractions of bodywall muscles (White et al., 1986; Kawano et al., 2011) (GapjunctFIG 7). In this instance, information flow involves parallel use of both chemical synapses and gap junctions. While AVA interneurons connect to all class A motor neurons in the nerve cord, AVB interneurons connect to all class B motor neurons. In the absence of functional electrical connections (encoded by unc-7 and unc-9 genes for these heteromeric gap junctions), mutant animals (unc-7 or unc-9 , or the double mutant) are unable to propagate smooth forward or backward motions, but instead show 'kinking' (severe body bending) in local zones. Electrical contacts between cell layers helps to switch between two opposing sets of ongoing neuronal and muscle activity (favoring either AVA + class A activity, or AVB + class B activity) to allow one set to predominate. Thus, sustained waves of signals pass along the nerve cord and muscles in one direction but not the other (Kawano et al., 2011; Liu et al., 2017).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1206, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9fd46465-991d-401e-a566-279c2d782055": {"__data__": {"id_": "9fd46465-991d-401e-a566-279c2d782055", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.4) Nervous System](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b3127383-be2c-431a-814b-ef7c3340accc", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.4) Nervous System](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "08ab2640dbcb08ce53da9a086457d3692bd80c0c372e063e2d253ae826c282ce", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "A variety of gap junctions has been noted for a pheromone-sensing circuit in the adult hermaphrodite nerve ring (Macosko et al., 2009) (GapjunctFIG 8). Here a single pair of interneurons (RMGL, RMGR) are connected to different sensors in the nose. Most connections rely on gap junctions (only) between the sensor and the interneuron (hub), though there are exceptions where chemical synapses sit parallel to electrical connections. The RMG interneurons become the key for balancing sensory inputs (Macosko et al., 2009). For instance, RMG integrates reception for several pheromones, detected by different receptor neurons, influencing the animal's response, where reception of any single pheromone is generally not sufficient to evoke a response (Jang et al., 2012). RMG then contacts many downstream neurons in the nerve ring and ventral cord, mostly via chemical synapses, to organize responses to those stimuli.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 915, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cb53b6b8-2cf6-4330-8e83-81afbe3c8459": {"__data__": {"id_": "cb53b6b8-2cf6-4330-8e83-81afbe3c8459", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.4) Nervous System](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8f5fc5f4-405f-4ca6-bb66-6adff2cb76f4", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.4) Nervous System](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "c71ee507700addf19bdd81ceda17f766db253dff659899a556f9111a1472aa32", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Most sensory neurons in the nematode have ciliated endings in either the nose or the extreme tail tip. However, the touch neuron sensors (ALM, PLM, AVM, PVM) for mild body touch have long sensory dendrites embedded in the bodywall, with receptive territories spanning up to half the body length (Chalfie et al., 1985). Inputs from anterior vs posterior stimuli are compared by pairs of interneurons, particularly the BDUs and command interneurons of the ventral cord, which are in position to compare the relative strength of touch stimuli received from either half of the body.\u00a0 While some synapses from sensors to these interneurons are chemical, several involve only gap junctions. Interestingly, BDU interneurons receive major gap junction inputs from anterior ALMs, and from long processes of the posterior PLMs in a unique lateral position close to the vulva (Zhang et al., 2013). Wnt signaling informs the development and targeting of lengthy PLM and BDU process extensions to bring the two classes together in a unique locale, where processes stop upon forming one large gap junction per side (BDUL to PLML, BDUR to PLMR).\u00a0 These isolated gap junctions were only discovered recently. Their connections are far removed from the influence of other neurons, away from the major nerve cords. How BDUs handle these different inputs from ALM and PLM is worthy of further study. Their chemical synapses are few, and concentrated in the nerve ring with rather diverse targets. Alternately, BDU might not be comparing touch dendrite inputs, but perhaps modulating excitability of two classes of sensors, ALM and PLM, via these electrical synapses.\n\n 4.4.2 Synapses within a layer", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1678, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1a7736af-3ca0-4647-8bd5-a217172385fc": {"__data__": {"id_": "1a7736af-3ca0-4647-8bd5-a217172385fc", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.4) Nervous System](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "91eb1969-fa1e-41fd-9c95-f080d85f8dcb", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.4) Nervous System](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "400068abe8afc507e4e0850835dc95ae65ef10960005aab29dbbdf1603b4f31a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Gap junctions commonly link multiple members of a neuron class, including left/right cell pairs in any layer (sensory cell pairs; interneuron pairs; motor neuron groups). Although chemical synapses can also play a similar role, gap junctions often predominate. Given the sparse network, we surmise that such gap junctions can equalize and/or prolong the activity in left/right pairs. They may also compensate where new stimuli have arisen unequally (in terms of sidedness), or even where some chemical synapses are missing or nonfunctional in the overall network. These recurrent contacts within layers are notable (Jarrell et al., 2012). Furthermore, except in special cases, left/right differences in cell activity between homologues are apparently rare in C. elegans. \n\n 4.4.2.1 Left/right balance and signal prolongation", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 824, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a7e4f01c-4963-4436-b527-05846c1e39d8": {"__data__": {"id_": "a7e4f01c-4963-4436-b527-05846c1e39d8", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.4) Nervous System](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "845f989a-8607-41e1-8c04-d658c88a431b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.4) Nervous System](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "c78ded81b08173f17a9f8bd34e3f7189498f09272f684ad615d5ebe5b1abb816", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "A few left/right pairs of sensory neurons are known to respond to different types of external signals. ASEL vs. ASER is the best known example (Luo et al., 2014; Bargmann, 2006). These chemosensory neurons in the nose detect different salts and water-soluble compounds in the animal's external environment, and are involved in chemotaxis behaviors. ASEL responds primarily to sodium, whereas ASER responds better to chloride and potassium. Interestingly, these two neurons are among the few bilateral homologues in the entire adult connectome that apparently do not form any gap junctions to one another (Altun et al., 2009).\u00a0 This circumstance reinforces the idea that gap junctions underlie synchronization, whereas the two ASE sensors probably operate independently to provide the animal with separable responses to different ions.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 834, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9b1161ac-0305-41e0-b38a-e229d14d4acb": {"__data__": {"id_": "9b1161ac-0305-41e0-b38a-e229d14d4acb", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.4) Nervous System](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b4e4b3b7-9ee5-4f84-b532-8fcef2635366", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.4) Nervous System](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "4d15f25ac7a74f6d7a1b94106f01395d97391900250d84dfb808549c219b7c5b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Another pair of olfactory neurons, AWCL/AWCR, have well described gap junctions in the lateral ganglia involving their somata in the late embryo and early L1 larva (see Section 3 Development), but later lose these connections to ASH somata (encoded by the innexin nsy-5) in the adult. These gap junctions are required during the time when the two AWC neurons adopt different cell fates, but are not present in adults, after their olfactory preferences have diverged (Chuang et al., 2007). Either AWC cell can adopt either cell fate, depending on a cascade of signaling involving this gap junction, but when nsy-5 is mutated, the two AWCs can chose identical cell fates. Given the small number of cells available, most sensory cells in C. elegans must respond to multiple extracellular signals (Bargmann, 2006; Rengarajan et al., 2016), unlike in higher animals, where sensory neurons are abundant, and each can express a single receptor type (Malnic et al., 1999).\u00a0 This is not feasible in C. elegans, where the typical sensory neuron expresses many different receptors. Perhaps the more surprising aspect is that so often sensory cell pairs still share gap junctions to their bilateral homologue, since they might have acquired more diverse sensory capabilities if more bilateral sensors could operate separately.\n\n 4.4.2.2 Motor neurons", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1338, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "08d6da33-7f4c-4673-ad59-4493942ec51a": {"__data__": {"id_": "08d6da33-7f4c-4673-ad59-4493942ec51a", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.4) Nervous System](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "20ccc985-a5f9-4c10-8d11-640c0986932d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.4) Nervous System](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "d8236d58f3028afe1c78e43aa13f6d736b3aaee8cc0d3e07305d3a761cdf06d5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Within the motor neuron layer, gap junctions are again prominent. In the nerve ring, small groups of homologues are coupled by gap junctions to allow coordinated activity; examples include the RMEs, RMDs and a few more. Gap junctions are also common between non-homologues among the sublateral motor neurons, such as SMB to SAA and SMD to RMD.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 343, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cf028a16-2372-423d-bef4-51ee77790752": {"__data__": {"id_": "cf028a16-2372-423d-bef4-51ee77790752", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.4) Nervous System](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "90499c39-1bdc-43a3-80b7-bf744c746bf2", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 4.4) Nervous System](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "af4cd69622ab54948639ae024ce9682a1bc7935800ebb2dbb3ad4266226970eb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Gap junctions are prominent among motor neurons that lie in sequential fashion along the length of the body in the two major motor nerves, the ventral and dorsal cords (GapjunctFIG 9) (White et al., 1986; Haspel and O'Donovan, 2012). Each motor nerve cord contains sets of 5-12 equivalent neurons each for several classes of motor cells, most having excitatory action onto bodywall muscles. Each excitatory motor neuron has a limited range along the body where it forms chemical neuromuscular junctions. Their ranges do not overlap within a given class, but instead motor neuron axons typically form a single gap junction at the limit of their range onto the next motor axon of the same type (but do not form any chemical synapses between these pairings).\u00a0 In some cases, gap junctions are also formed at the extended limits of their dendrites. Thus, signals can be conducted along the motor nerves as separate streams for each class of motor cell, some of which underlie waves of contraction propagating from head to tail (class B excitors, including DB, VB), while others propagate signals from tail to head (class A excitors, including DA, VA).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1147, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "818412f2-a7d8-4f70-a7bf-70cb4c05b700": {"__data__": {"id_": "818412f2-a7d8-4f70-a7bf-70cb4c05b700", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 5) References](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8e7dd891-f7cf-401f-b39c-8037e2e14ba8", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Gap Junctions, Section 5) References](https://www.wormatlas.org/hermaphrodite/gapjunctions/Gapjunctframeset.html)"}, "hash": "d5b18caec26766aab0263016a4dc4ed4505b157b3c128f9f30df22af4a760005", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "This chapter should be cited as: Hall, D.H. 2018. Gap junctions. In WormAtlas. doi:10.3908/wormatlas.1.25\n\n We thank Chris Crocker for his help in preparing the figures. \n\n Edited for the web by Laura A. Herndon. Last revision: February 19. 2020.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 246, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "bc923bdf-5c98-4735-ae6d-206a7c1b65d8": {"__data__": {"id_": "bc923bdf-5c98-4735-ae6d-206a7c1b65d8", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [The Cuticle, Section 1) General Description](https://www.wormatlas.org/hermaphrodite/cuticle/Cutframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b452e302-cbd1-4cdb-aa20-6e620a6ac9d6", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [The Cuticle, Section 1) General Description](https://www.wormatlas.org/hermaphrodite/cuticle/Cutframeset.html)"}, "hash": "94a751e93cce40e2fa24ccd4e5b41c6ec995b3122b9a57e007a4c262e8d012a9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The outer surface of the animal is covered by a tough, but flexible, extracellular cuticle (CutFIG 1). This cuticle protects the animal from the environment, maintains body shape, and permits motility by acting as an external skeleton. The cuticle is secreted by the epithelial cells covering the body (hypodermis, seam cells) and by interfacial cells lining the four major openings to the exterior (anus, excretory pore, vulva and pharynx). The cuticle surface is covered with a surface coat (glycocalyx) that is thought to be secreted by gland cells (the excretory cell, pharyngeal gland cells, or the amphid and phasmid support cells) (Nelson et al., 1983; Jones and Baillie, 1995; Page and Johnstone, 2007). At each larval stage, an entirely new cuticle is generated and the old cuticle is shed, allowing for growth. Significantly, cuticles of each stage differ in their surface protein expression, layer number, relative thickness, and composition, presumably to accommodate for the changing developmental needs and environmental conditions experienced during the life of the animal.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1088, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fa733b8f-e7d3-42dc-8b2c-85291254a268": {"__data__": {"id_": "fa733b8f-e7d3-42dc-8b2c-85291254a268", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [The Cuticle, Section 2) Body Cuticle Surface Morphology](https://www.wormatlas.org/hermaphrodite/cuticle/Cutframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e125880c-a87c-4a02-877b-acbc842c1f9d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [The Cuticle, Section 2) Body Cuticle Surface Morphology](https://www.wormatlas.org/hermaphrodite/cuticle/Cutframeset.html)"}, "hash": "ec275c4bbf9d00170e82473492182e0a51b55a74c22115efcdc28dbb29e2fd5e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The cuticle surface bears shallow, circumferential-oriented furrows (CutFIG 1, CutFIG 2A&B) (Chitwood and Chitwood, 1950; Cox et al., 1981a). The ridges on either side of the furrows are called annuli. In L1, dauer, and adult cuticles annulations are interrupted laterally by longitudinally oriented ridges called alae that are generated by cells of the lateral seam beneath (CutFIG 1, CutFIG 2B) (see Epithelial system - Seam cells). The cuticle surface is also marked by holes and swellings where some neuronal cilia are exposed to the exterior (e.g., amphids and inner labial sensory organs) (CutFIG 2A) or lie just beneath the surface, respectively (e.g., the outer labial sensory organs, CutFIG 2A, or deirids, CutFIG 2B; see also NeuroTABLE 1).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 750, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a075bc2c-f1bc-4105-a9de-e09a9fdfb0e7": {"__data__": {"id_": "a075bc2c-f1bc-4105-a9de-e09a9fdfb0e7", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [The Cuticle, Section 3.1) Cuticle Layers](https://www.wormatlas.org/hermaphrodite/cuticle/Cutframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6976b53b-4fd5-49ba-83af-dd7936ddef37", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [The Cuticle, Section 3.1) Cuticle Layers](https://www.wormatlas.org/hermaphrodite/cuticle/Cutframeset.html)"}, "hash": "bb9fc9e3199d95ade4d52c4a0a3b49bbe5b51b710695a26a681baec23e54df33", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The cuticle consists of layers or zones that differ in structure and composition. Layers can be distinguished by electron microscopy (EM) cross section as well as en face by several modalities (e.g., thin section and deep etching; CutFIG 3, CutFIG 4A&B). The adult cuticle is approximately 0.5 \u03bcm in thickness (Cox et al., 1981a) and is organized into five major layers or zones: the surface coat, the epicuticle layer, and the cortical, medial and basal zones (Cox et al., 1981a; 1981b, Bird and Bird, 1991).\u00a0\u00a0With aging, the thickness of the adult cuticle increases due to expansion of the basal zone (Herndon et al., 2002).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 626, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "824957b4-ee0e-4272-bb27-efaaa2663330": {"__data__": {"id_": "824957b4-ee0e-4272-bb27-efaaa2663330", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [The Cuticle, Section 3.1) Cuticle Layers](https://www.wormatlas.org/hermaphrodite/cuticle/Cutframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d2602be9-7480-4d1e-92b4-e1e3df438542", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [The Cuticle, Section 3.1) Cuticle Layers](https://www.wormatlas.org/hermaphrodite/cuticle/Cutframeset.html)"}, "hash": "a46d625174f355bc5b2aea122672684dfceedeaf0df86bfdb1672393f4195696", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "3.2 Cuticle Composition", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 23, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c465386e-0abd-4a51-a15f-aab0afb52544": {"__data__": {"id_": "c465386e-0abd-4a51-a15f-aab0afb52544", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [The Cuticle, Section 3.2) Cuticle Composition](https://www.wormatlas.org/hermaphrodite/cuticle/Cutframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2f98bd70-0f11-41ef-8518-77d0d4cc8a1c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [The Cuticle, Section 3.2) Cuticle Composition](https://www.wormatlas.org/hermaphrodite/cuticle/Cutframeset.html)"}, "hash": "83b657d690ed6a0f76c8343a524ab2b5f5fa3efd7298144ca7ae3fcf6e586f09", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The different layers of the cuticle appear to consist of distinct molecular assemblies that impart different qualities. The wide range of phenotypes associated with mutations in cuticle components genes suggests a high degree of functional specialization among cuticle proteins and the layers to which they contribute. Mutant phenotypes range from abnormal surface epitope expression (Srf, surface antigenicity abnormal phenotype) and pathogen resistance (e.g. Bus, bacterially unswollen) to altered body shape (Rol, roller; Dpy, dumpy; Sqt, squat; Lon, long) or abnormal cuticle morphology (Bli, blister) (Brenner, 1974; Higgins and Hirsh, 1977; Kusch and Edgar 1986; Politz et al., 1990; Link et al., 1992; Kramer and Johnson, 1993; Nicholas and Hodgkin, 2004). The most abundant structural components of cuticle are collagens and the non-collagenous cuticulins (Sebastiano et al., 1991; Lewis et al., 1994; Kramer, 1997). These molecules assemble into the relatively insoluble, higher-order complexes that form the cuticle matrix. Collagens COL-19 (CutFIG 5A) and BLI-1 (CutFIG 5B) localize to the adult cortical layer and (Liu et al., 1995; Thein et al., 2003) medial layer struts, respectively (J. Crew and J.M. Kramer, pers. comm.); DPY-7 (CutFIG 5C) localizes to the furrows in all stages (McMahon et al., 2003). Although few have been characterized, the cuticle probably also contains many soluble proteins such as enzymes involved in post-secretion modification and cross-linking of matrix proteins or structural proteins associated with the surface coat (e.g. mucins). Lipids and glycolipids are found in the epicuticle layer, an atypical membrane. Carbohydrates are associated with glycosylated proteins of the matrix and of the surface coat (Blaxter and Robertson, 1998).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1783, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "54a21b8a-4dbc-49be-861d-8eeeaff592e5": {"__data__": {"id_": "54a21b8a-4dbc-49be-861d-8eeeaff592e5", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [The Cuticle, Section 3.2) Cuticle Composition](https://www.wormatlas.org/hermaphrodite/cuticle/Cutframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "046b460a-2015-4bcf-9fe0-6292178f4822", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [The Cuticle, Section 3.2) Cuticle Composition](https://www.wormatlas.org/hermaphrodite/cuticle/Cutframeset.html)"}, "hash": "7999ceb8ff6e0d4a024399b78594cda5d0fc5f49480097a5c6090550a52bebd9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Larval stage cuticles differ from adult in the type of layers present or their relative thickness (CutFIG 6 and DCutFIG 1). The dauer cuticle is further distinguished from those of other stages in being less permeable and proportionally thicker (10.2% of the animal's cross sectional area; c.f. 4.4% for other stages) because of a reduction in body diameter and an increase in epicuticle layer thickness (Cassada and Russell, 1975; Cox et al., 1981b). See also Dauer Cuticle Chapter.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 483, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e1655209-c8c9-4646-bc19-70dbd6ef4f4e": {"__data__": {"id_": "e1655209-c8c9-4646-bc19-70dbd6ef4f4e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [The Cuticle, Section 4) Cuticle Generated By Other Tissue](https://www.wormatlas.org/hermaphrodite/cuticle/Cutframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "238ccacd-d235-4a23-8aba-0e9d1e13b4d9", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [The Cuticle, Section 4) Cuticle Generated By Other Tissue](https://www.wormatlas.org/hermaphrodite/cuticle/Cutframeset.html)"}, "hash": "a29d3e8fd3db4b7cc6482a937ba21154b9e12455c9bad738ccd48fb3646260ce", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The major openings of the animal are also cuticle-lined: the buccal cavity and pharynx (see Alimentary system - Pharynx), the vulva (see Reproductive system - Egg-laying Apparatus), the rectum (see Alimentary system - Rectum and Anus) and the excretory duct and pore (see Excretory system). These cuticles are secreted by underlying cells that are generally epithelial, although in the case of the buccal cavity and pharynx, other cell types may contribute (e.g. pharyngeal muscle cells). In contrast to body cuticle, cuticles that line the openings do not appear to be composed of layers. However, some contain specialized cuticular elements. The most striking examples are seen in the pharyngeal cuticle, which contains at least four different types of elements: bridging cuticle, flaps, grinder, sieve, and channels (CutFIG 7A, CutFIG 7B-E; Albertson and Thomson, 1976; Wright and Thomson, 1981). The excretory duct and pore cuticles also contain regions of distinctive patterning (CutFIG 8) These may serve to strengthen the pore and to keep it open.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1054, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7627377a-2dbb-4411-bdcd-0c3957ee9875": {"__data__": {"id_": "7627377a-2dbb-4411-bdcd-0c3957ee9875", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [The Cuticle, Section 5) Cuticle Production and Molting](https://www.wormatlas.org/hermaphrodite/cuticle/Cutframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9dc68f29-7a7f-4e4f-ab28-e0e89aa9d6a4", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [The Cuticle, Section 5) Cuticle Production and Molting](https://www.wormatlas.org/hermaphrodite/cuticle/Cutframeset.html)"}, "hash": "3b2a001dd2a3aaebd98176fed5581a7782f7012ccabc90517ce570b6452b581c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The first cuticle, the L1 cuticle, is laid down at the time of embryonic elongation. Contraction of circumferential actin filament bundles, which lie beneath the surface of the hypodermal apical membrane, induce elongation of the embryo and simultaneously produces ridges and furrows in the hypodermis and an overlying lipid layer called the embryonic sheath (Priess and Hirsh, 1986). This surface is thought to serve as a template for cuticle annulations (CutFIG 9A) (Costa et al., 1997).\u00a0 A similar contractile mechanism may be employed to pattern later stage cuticles and, possibly, the formation of alae.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 608, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f77da06f-7e6a-45d6-a4a5-49eaada3558d": {"__data__": {"id_": "f77da06f-7e6a-45d6-a4a5-49eaada3558d", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [The Cuticle, Section 5) Cuticle Production and Molting](https://www.wormatlas.org/hermaphrodite/cuticle/Cutframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b835a57d-c2fe-412c-ab1b-d6d86498f851", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [The Cuticle, Section 5) Cuticle Production and Molting](https://www.wormatlas.org/hermaphrodite/cuticle/Cutframeset.html)"}, "hash": "fe7328567627b0f57d078bf9575495dacf759ee987b48354a440679ca6a61b9a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Following hatching are four post-embryonic molts whereby an entirely new cuticle is synthesized and the old cuticle is shed. The new cuticle is laid down beneath the existing cuticle, with the outer layers synthesized first and the inner layers last. Seam cells, and to a lesser extent hypodermal cells, acquire large Golgi and have vesicles containing densely staining material, consistent with the notion that high levels of protein synthesis and secretion occur at this time (Singh and Sulston, 1978). The new cuticle is initially highly convoluted and the underlying hypodermis contains folds known as plicae (CutFIG 9B).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 625, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "af2b7aff-1c9a-42bf-a9e0-92c8556abc0d": {"__data__": {"id_": "af2b7aff-1c9a-42bf-a9e0-92c8556abc0d", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [The Cuticle, Section 5) Cuticle Production and Molting](https://www.wormatlas.org/hermaphrodite/cuticle/Cutframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e50c552d-1e04-4c3f-961f-a805a9f35515", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [The Cuticle, Section 5) Cuticle Production and Molting](https://www.wormatlas.org/hermaphrodite/cuticle/Cutframeset.html)"}, "hash": "266e074b62a002d30ee6c1100c4d26bc8270e0558926fb797fdc1d12f08058cd", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Consistent with the cyclic nature of the molting process, synthesis of cuticle components is low between molts and high prior to molts (Cox et al., 1981c). Transcriptional analysis of collagen gene activity reveals multiphasic waves of early (e.g. dpy-7), middle (sqt-1 , dpy-13), and late (col-12) gene expression. It is hypothesized that collagens that are produced cotemporally may be incorporated into the same heteromeric complex or cuticle substructure (Cox et al., 1981c; Cox and Hirsh, 1985; Park and Kramer, 1994; Johnstone and Barry, 1996; McMahon et al., 2003). Some cuticle proteins are synthesized at every molt (e.g. COL-12) whereas others are stage-specific e.g., adult-specific COL-19 and BLI-1 (CutFIG 5A&B).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 725, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "376fa10c-b82d-4ece-b251-8c4dae71c43b": {"__data__": {"id_": "376fa10c-b82d-4ece-b251-8c4dae71c43b", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [The Cuticle, Section 5) Cuticle Production and Molting](https://www.wormatlas.org/hermaphrodite/cuticle/Cutframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c3fd3c5b-c4d1-473c-8840-38b189c5e710", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [The Cuticle, Section 5) Cuticle Production and Molting](https://www.wormatlas.org/hermaphrodite/cuticle/Cutframeset.html)"}, "hash": "c453fd677bfd4510536aec4fa9c8fbf9f9f2d8f103f21d8eeb77fb12b6d9f797", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Molting consists of two phases: lethargus, the period of inactivity preceding cuticle shedding, and ecdysis or cuticle shedding (Singh and Sulston, 1978). In the first half of lethargus pharyngeal pumping and locomotion decrease and seam cells lose their granular appearance. Immobility is thought to result from the separation of the basal zone in the old cuticle from the underlying hypodermis. Loosening of the old cuticle begins around the head, then moves to the buccal cavity and the tail. In the second half of lethargus, the worm begins to spin and flip around its long axis. The pharynx contracts and its cuticle lining breaks; the posterior half passes into the intestine and the anterior half is expelled and shed with the body cuticle. At this time, refractile granules are apparent in the pharyngeal gland cell processes and are thought to play a role in ecdysis.\u00a0 As in insects, molting in C. elegans appears to be regulated by nuclear hormone receptors (Kostrouchova et al., 1998, 2001).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1002, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6c1171a9-5fe2-412b-ba19-861948fb19a6": {"__data__": {"id_": "6c1171a9-5fe2-412b-ba19-861948fb19a6", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [The Cuticle, Section 6) Cuticle Attachment Complexes](https://www.wormatlas.org/hermaphrodite/cuticle/Cutframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "218fa342-c1e4-4c46-a29d-f389a582ca28", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [The Cuticle, Section 6) Cuticle Attachment Complexes](https://www.wormatlas.org/hermaphrodite/cuticle/Cutframeset.html)"}, "hash": "b6df1d632be360416ca7eaff4cd1b2491ea25bddae325db9401ad08e074fa7a3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Locomotion requires the transmission of contractile force from body wall muscle to the cuticle.This force is transmitted through a series of mechanical linkages connecting body wall muscle, basal lamina, hypodermis and cuticle (CutFIG 10, CutFIG 11). The inner layer of the cuticle is attached to the apical hypodermal membrane through electron-dense attachment complexes, called hemidesmosomes, from which intermediate filaments extend into the cytoplasm. Similar complexes are also present on the basal hypodermal membrane and when apical and basal complexes are in register, a fibrous organelle (FO) is formed. Anchoring fibrils extend from FOs into the extracellular basal lamina, which is linked, in turn, to muscles through the M line and dense bodies of the sarcomere (Francis and Waterston, 1991; Hresko et al., 1994, 1999; Bercher et al., 2001; Hong et al., 2001; Hahn and Labouesse, 2001) (see also Somatic Muscle). Similar junctional complexes are also associated with non-body wall muscles (e.g. of the vulva, pharynx and rectum) and with non-muscular cells that also make tight transhypodermal contact with the cuticle such as the excretory pore, touch neuron processes, amphids and phasmids (Bercher et al., 2001).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1228, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "64c71441-12d3-45ae-92a6-7e1669b0a45c": {"__data__": {"id_": "64c71441-12d3-45ae-92a6-7e1669b0a45c", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [The Cuticle, Section 7) Cuticle Mutants](https://www.wormatlas.org/hermaphrodite/cuticle/Cutframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3fecb585-16f2-4a4e-bdc6-f9ba1f9c512a", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [The Cuticle, Section 7) Cuticle Mutants](https://www.wormatlas.org/hermaphrodite/cuticle/Cutframeset.html)"}, "hash": "9c1c489ece859d61134319d847db2839a6288f15ab2a14d98fe892a6908ba9ea", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Proper cuticle formation and function is regulated by a number of different genes, many of which are mentioned above and have been described in detail previously (for review see Page and Johnstone, 2007 in WormBook). When cuticle formation is altered, this can lead the changes in the appearance of the animal, producing phynotypes such as long or dumpy (CutFIG 12). Addtionally, animals can exhibit defects in the surface as seen in the structure of their annuli, furrows and alae (CutFIG 12 & CutFIG 13). These altered cuticle structures can also result in molting and movement defects (CutFIG 13).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 600, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9995b6e4-9953-4414-8bf9-8462773bee96": {"__data__": {"id_": "9995b6e4-9953-4414-8bf9-8462773bee96", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Muscles, Section 1) Nematode Somatic Muscle](https://www.wormatlas.org/hermaphrodite/musclesomatic/MusSomaticframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "01cbbb7a-ded7-46d8-97be-64c1089fc697", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Muscles, Section 1) Nematode Somatic Muscle](https://www.wormatlas.org/hermaphrodite/musclesomatic/MusSomaticframeset.html)"}, "hash": "92cda3964aae243815bc0ae2b753227f4489b63c946bbecc60adace000fab5c2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In C. elegans, the 95 rhomboid-shaped body wall muscle cells are arranged as staggered pairs in four longitudinal bundles located in four quadrants (MusFIG 7). Three of these bundles (DL, DR, VR) contain 24 cells each, whereas the VL bundle contains 23 cells. This asymmetry appears to result from a gap on the ventral left quadrant of the embryo, slightly posterior to the gonad primordium (Sulston and Horvitz, 1977). Muscles are always separated from the underlying hypodermis and nervous tissue by a thin (approximately 20 nm) basal lamina (BL). This BL remains intact within the synaptic regions, except for NMJs made in the nerve ring between the RIML/R motor neurons and their target muscle arms. A typical somatic muscle cell has three parts: the contractile filament lattice (spindle), a noncontractile body (muscle belly) containing the nucleus and the cytoplasm with mitochondria, and the muscle arms, slender processes that extend to either ventral or dorsal nerve cords or the nerve ring (MusFIG 8) (see Introduction to Muscle). Somatic muscle nuclei are oblong (ovoid), intermediate in size between neuronal and hypodermal nuclei, and have a small, spherical nucleolus. Viewed by differential interference contrast (DIC) microscopy, their nucleoplasm appears granular in L1, but becomes smooth in L2 and remains so throughout the rest of the development (Sulston and Horvitz, 1977).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1396, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "660ffb31-0c85-4ab2-91b9-ba1c6b38f3e4": {"__data__": {"id_": "660ffb31-0c85-4ab2-91b9-ba1c6b38f3e4", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Muscles, Section 2) Structure of Somatic Muscle](https://www.wormatlas.org/hermaphrodite/musclesomatic/MusSomaticframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4f9777f8-b1c7-4933-92b9-c2c4289f3e7b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Muscles, Section 2) Structure of Somatic Muscle](https://www.wormatlas.org/hermaphrodite/musclesomatic/MusSomaticframeset.html)"}, "hash": "c0efbee6228c4c47c03a998e06879b928cf757dc1de34c13dbbd5f0a6aeb7487", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The body wall muscle of C. elegans, as in all other nematodes, is obliquely striated (MusFIG 8). Although the filaments themselves are oriented parallel to the longitudinal axis of the muscle cell, adjacent structural units (M lines and DBs) are offset from one another by more than a micron, rather than being in register as in vertebrate cross-striated muscle (Waterston, 1988; Bird and Bird, 1991). Therefore, the observed A\u00e2\u0080\u0093I striations occur at an angle of 5\u00e2\u0080\u00937\u00c2\u00b0 with respect to the longitudinal axes of the filaments and the muscle cell, in comparison to 90\u00c2\u00b0 in vertebrate cross-striated muscle (MusFIG 9 and MusTABLE 1). This oblique arrangement of the sarcomeres is suggested to create a more evenly distributed muscle force application over the BL and cuticle, allowing for smooth bending of the body rather than kinking (Burr and Gans, 1998). Each somatic muscle cell is attached basally to the underlying hypodermis and cuticle and laterally to the neighboring muscle cells through three distinct PAT-2/PAT-3 integrin-containing attachment complexes. These include DBs, M lines, and lateral attachment plaques.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1126, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d301099a-6026-4c8b-8353-db04c392a550": {"__data__": {"id_": "d301099a-6026-4c8b-8353-db04c392a550", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Muscles, Section 2.1) Basal Attachments](https://www.wormatlas.org/hermaphrodite/musclesomatic/MusSomaticframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5afcd42f-ec22-4faa-917a-16f978fc9258", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Muscles, Section 2.1) Basal Attachments](https://www.wormatlas.org/hermaphrodite/musclesomatic/MusSomaticframeset.html)"}, "hash": "c3ab94209214270cb2b5882a83e3f304ff6aea325e72627cdd9fecc612c8259d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In C. elegans, the myofilament lattice of each contractile unit is anchored to the muscle cell membrane and adjacent BL by DB and M lines, which are highly ordered, regularly spaced structures that extend from the cytoplasm to the plasma membrane (MusFIG 10). DB and M lines are homologous to vertebrate focal adhesion plaques and contain many of the cytoskeletal adaptor proteins of these integrin-mediated attachments, including talin, PAT-6/actopaxin, PAT-4/ILK, and UNC-97/PINCH. DBs also share some components with muscle\u00e2\u0080\u0093muscle attachment plaques (Francis and Waterston, 1985).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 585, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b1244e88-a5e9-4cec-b15a-926eaf4e25a6": {"__data__": {"id_": "b1244e88-a5e9-4cec-b15a-926eaf4e25a6", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Muscles, Section 2.1) Basal Attachments](https://www.wormatlas.org/hermaphrodite/musclesomatic/MusSomaticframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cd35c1a5-a3df-4dd4-9ee6-2f273cbc1767", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Muscles, Section 2.1) Basal Attachments](https://www.wormatlas.org/hermaphrodite/musclesomatic/MusSomaticframeset.html)"}, "hash": "65f92e122dd2dd95c33adb8d80d1b6947837cdeb85b3e35d14ca52c90bdd4051", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "At the plasma membrane, DB and M lines are mechanically linked to the outside cuticle through BL components and hypodermal fibrous organelles (FOs) (MusFIG 11 and MusFIG 12) (Waterston, 1988; Francis and Waterston, 1991; Moerman and Fire, 1997; Coutu Hresko et al., 1999; Hahn and Labouesse, 2001; Cox and Hardin, 2004). Perlecan and collagen IV concentrate in the BL underneath each DB and M line, which align with FOs of the hypodermis. FOs are also known as transepidermal attachments and are homologous to vertebrate hemidesmosomes (HD) that anchor the intermediate filament network to the plasma membrane and BL (Ding et al., 2004; Labouesse, 2006). Like HD, they are seen as two electron-dense plaques, one on the inside of each hypodermal plasma membrane, which are connected by cytoplasmic intermediate filaments that span the width of the hypodermis (MusFIG 11). FOs are restricted to the thin hypodermal regions that overlie muscle cells, and they form concurrently with muscle development. In early embryonic stages, they are localized into longitudinal strips; however, during elongation of the embryo and as circumferential actin bundles form in hypodermal cells, they change into a circumferential stripe pattern. This pattern continues through larval and adult stages (Ding et al., 2004).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1303, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b4ffbced-28b8-473c-8798-a2c9b5b31df8": {"__data__": {"id_": "b4ffbced-28b8-473c-8798-a2c9b5b31df8", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Muscles, Section 2.1) Basal Attachments](https://www.wormatlas.org/hermaphrodite/musclesomatic/MusSomaticframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "30dfe0fd-6b62-4c8e-adf3-2bb5cea20146", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Muscles, Section 2.1) Basal Attachments](https://www.wormatlas.org/hermaphrodite/musclesomatic/MusSomaticframeset.html)"}, "hash": "6210d78959a85079a18341ac92a7ccc477256a3fa55ae4e0c9d00c1fb605004a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Loss of function in components of DB and M lines frequently results in detachment of body wall muscles from the cuticle, supporting the hypothesis that these attachment structures function to promote mechanical strength between the muscle and hypodermis (Gatewood and Bucher, 1997; Plenefisch et al., 2000).\n\n 2.2 Attachment Plaques (Lateral Attachments)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 354, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "97e3e829-9555-40b4-b4b6-c96b74508f0a": {"__data__": {"id_": "97e3e829-9555-40b4-b4b6-c96b74508f0a", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Muscles, Section 2.2) Attachment Plaques (Lateral Attachments)](https://www.wormatlas.org/hermaphrodite/musclesomatic/MusSomaticframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6d1b6987-e695-437a-aa2b-12e1c38bb64a", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Muscles, Section 2.2) Attachment Plaques (Lateral Attachments)](https://www.wormatlas.org/hermaphrodite/musclesomatic/MusSomaticframeset.html)"}, "hash": "7a0b38fe2375b4910909cd01c3dfd33b70c2c45ddc27fcd63f594847cd9b3d7b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Similar to myotendinous junctions of vertebrate skeletal muscle, the ends of C. elegans somatic muscle cells contain thin (actin) filament attachment plaques (the ends of the terminal half I bands at which microfilaments are attached to the cytoplasmic surface of the plasma membrane), which are most similar to DBs (MusFIG 13). By means of attachment plaques, each of the muscle cells adheres tightly to adjacent muscle cells within one quadrant (Francis and Waterston, 1991; Coutu Hresko et al., 1994). Although this may allow for some tension to be transmitted longitudinally between cells, the bulk of the tension created by muscle contraction is transferred to the exoskeleton/cuticle through basal attachments that are distributed along the entire length of the cell (Francis and Waterston, 1985; Woo et al., 2004).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 821, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "77ef165e-cc42-41c8-8662-51cb92d2804f": {"__data__": {"id_": "77ef165e-cc42-41c8-8662-51cb92d2804f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Muscles, Section 3) Development of Somatic Muscle](https://www.wormatlas.org/hermaphrodite/musclesomatic/MusSomaticframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2ca7f791-4c6d-4152-b20b-b1bb7c0cae6d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Muscles, Section 3) Development of Somatic Muscle](https://www.wormatlas.org/hermaphrodite/musclesomatic/MusSomaticframeset.html)"}, "hash": "ef3ce39a2bc165d783b16f3e0d4993536c40c39f5d09b44d8f843303d851663d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The body wall muscle cells are derived from D, C, AB, and MS cell lineages. At hatching, 81 of the 95 cells are present. Fourteen more muscle cells are generated post-embryonically from the MSapaapp lineage (MusFIG 14 , MusFIG 15A and MusFIG 15B) (Sulston and Horvitz, 1977; Sulston et al., 1983). Of the 81 body muscles of the newly hatched larva, 80 are generated in symmetrical fashion from MS, C, and D lineages. Twenty come from the D blast cell, which generates body muscle cells exclusively, 16 from Cp, 16 from Ca, 9 from MSpp, 6 from MSpa, 9 from MSap, and 4 from MSaa (Sulston et al., 1983). The remaining cell is generated by ABprpppppa and is one of a group of four muscles generated preanally by ABp(l/r)pppppa lineages (the other three cells become the anal depressor muscle, the sphincter muscle, and one of the two stomatointestinal muscles).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 858, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5975d396-7fdd-4c8f-96ee-6ee5d42c6cee": {"__data__": {"id_": "5975d396-7fdd-4c8f-96ee-6ee5d42c6cee", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Muscles, Section 3) Development of Somatic Muscle](https://www.wormatlas.org/hermaphrodite/musclesomatic/MusSomaticframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1d2aac2a-708a-4351-817d-0a7fea073c51", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Muscles, Section 3) Development of Somatic Muscle](https://www.wormatlas.org/hermaphrodite/musclesomatic/MusSomaticframeset.html)"}, "hash": "079fff97e8c38b3b9d411d537b0126e960cc9003d6994cecac4b8bc95f6a4447", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Myoblasts are born after the end of gastrulation at about 290 minutes of embryonic development (MusFIG 14 and MusTABLE 2). At this stage, muscle cells lie in two lateral rows next to the seam cells, and some muscle cells have not yet undergone their terminal divisions. During this time, hemidesmosome components start to accumulate in the hypodermis in a diffuse fashion and muscle cells start accumulating muscle components diffusely. Subsequently, at about 350 minutes of development, the muscle cells migrate dorsally and ventrally to contact the ventral and dorsal hypodermis (Coutu Hresko et al., 1994; 1999). All muscle cells finish their divisions before assuming their final positions. Cell\u00e2\u0080\u0093cell contact induces the components of the muscle contractile apparatus to coalesce at the membrane near the contact points, and fibrous organelle components (MH5 protein, intermediate filaments) become restricted to specific regions of the hypodermis adjacent to muscle. BL components are initially recruited to regions of contact between muscle cells. Hypodermal myotactin then accumulates adjacent to where the contractile apparatus is forming in the muscle. By the twofold stage of development, muscle cells become flattened and muscle attachment and myofilament lattice assembly begins, following positional cues laid down in the BL and muscle cell membrane (Coutu Hresko et al., 1994; Williams and Waterston, 1994; Moerman and Williams, 2006). UNC-52/perlecan in BL initiates and is essential in the assembly of both DB and M-line components. In mutants that lack UNC-52, all subsequent steps of sarcomere development are blocked. Then, integrin heterodimers polarize to the basal membrane of the muscle and aggregate into a series of organized focal contacts in each muscle quadrant, in correspondence with the UNC-52 sites. Next, other components of the attachment complexes, such as PAT-4/ILK and PAT-6/actopaxin, are recruited to these focal contacts. Recruitment of ILK initiates divergence into distinct actin and myosin filament anchorage sites as the DB and M lines, respectively (Moerman and Williams, 2006). In the final step, actin and myosin filaments are recruited to these proto-DB and M-line complexes, respectively, at the basal plasma membrane. As the contacts mature, they form the highly ordered, recognizable series of DB and M lines. Sarcomeres then become organized into oblique striations, and the interlocking arrangement of the rhomboid-shaped body wall muscle cells in separate bundles becomes apparent. At the earliest stage at which individual muscle cells become discernable, each cell is two A bands wide and the filaments are about 5 \u00ce\u00bcm long (Moerman and Fire, 1997). During this time, myotactin remains adjacent to the forming contractile apparatus, and its organization follows the oblique striations of the muscle. In contrast, components of fibrous organelles become organized in circumferentially oriented bands restricted to regions where hypodermis is adjacent to muscle. By the threefold stage (520 min after first cleavage of the embryo at 25\u00c2\u00b0C), myotactin is seen to colocalize with fibrous organelle components in these bands (Coutu Hresko et al., 1999). Muscle cell mass increases at each larval stage such that in the adult, each muscle cell may have grown to be as wide as 10 A bands and becomes approximately 100 \u00ce\u00bcm long. Individual filaments in the adult are 10 \u00ce\u00bcm long, and DB and M lines have also increased in size with larger integrin clusters (Moerman and Williams, 2006).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 3536, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "152d3cdc-fe56-4dcc-b889-4296d2fd4d42": {"__data__": {"id_": "152d3cdc-fe56-4dcc-b889-4296d2fd4d42", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Muscles, Section 3) Development of Somatic Muscle](https://www.wormatlas.org/hermaphrodite/musclesomatic/MusSomaticframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c282322d-7d22-4e5d-9563-317bb9f30495", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Muscles, Section 3) Development of Somatic Muscle](https://www.wormatlas.org/hermaphrodite/musclesomatic/MusSomaticframeset.html)"}, "hash": "37afa2757c0ed2666a94004611e100943ebe4146cf086bdc98070cafec0d7c85", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "During their formation in the embryos, all three types of attachment complexes look similar as electron-dense plaques. It is only during postembryonic larval stages that DB and M lines acquire their finger-like shapes by projecting into the cytoplasm from the plasma membrane. For DB, this projection coincides with the addition of \u00ce\u00b1-actinin into the structure more distal from the membrane (Francis and Waterston, 1985; Barstead and Waterston, 1991; Moerman and Williams, 2006).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 480, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f40c54ba-293c-404e-818f-79f3debf29ef": {"__data__": {"id_": "f40c54ba-293c-404e-818f-79f3debf29ef", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Muscles, Section 3) Development of Somatic Muscle](https://www.wormatlas.org/hermaphrodite/musclesomatic/MusSomaticframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cd929ba8-034c-4fc4-846b-7cb1a809ba03", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Muscles, Section 3) Development of Somatic Muscle](https://www.wormatlas.org/hermaphrodite/musclesomatic/MusSomaticframeset.html)"}, "hash": "096bdde024f35248564f644c0df264bdb6923a2a694eed0a5091015ee71e5a9a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Mutants with severe defects in sarcomere assembly become paralyzed with arrested elongation at the twofold stage (pat phenotype) of embryogenesis and fail to display any flipping motions (Williams and Waterston, 1994).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 218, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2345cca6-4e13-4c6f-91e7-27c6f71dad11": {"__data__": {"id_": "2345cca6-4e13-4c6f-91e7-27c6f71dad11", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Muscles, Section 4) Muscle Basal Lamina (Basement Membrane)](https://www.wormatlas.org/hermaphrodite/musclesomatic/MusSomaticframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b20004c4-90bf-4399-881f-35d7d0275f68", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Muscles, Section 4) Muscle Basal Lamina (Basement Membrane)](https://www.wormatlas.org/hermaphrodite/musclesomatic/MusSomaticframeset.html)"}, "hash": "e7e2e79795e151ee12be535fbc3d79c51c9703f82a1706589c3918b89b08ba0a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "As in other organisms, BL are thin sheets of specialized extracellular matrices that contain type IV collagen, laminin, nidogen, SPARC, and perlecan in C. elegans. Somatic muscle quadrants in the body run inside tubes of BL, which separates them from the pseudocoelomic cavity and underlying hypodermis and nervous tissue. The neuronal processes that run from the ventral side to the dorsal side (commissures) extend under this BL and between muscle and hypodermis. In the head, the BL is extended around the muscle arm plate and separates the muscle arms from the nerve ring. This extension of BL terminates onto the cylinder of sheet-like processes of the GLR cells, anterior to the nerve ring (White et al., 1986).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 717, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6387bc5d-d636-4c44-b54d-cadb58d567b7": {"__data__": {"id_": "6387bc5d-d636-4c44-b54d-cadb58d567b7", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Muscles, Section 5) Innervation of Somatic Muscle](https://www.wormatlas.org/hermaphrodite/musclesomatic/MusSomaticframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a134a352-a7e5-43a7-8b91-67e28485403e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Muscles, Section 5) Innervation of Somatic Muscle](https://www.wormatlas.org/hermaphrodite/musclesomatic/MusSomaticframeset.html)"}, "hash": "732f32c907118185a3cbf07f29649d4b77159464b4e1f6c251fd1a634f16e601", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Depending on the basis of their synaptic input, somatic muscles fall into three groups: (1) The anteriormost four somatic muscle cells in each quadrant (head muscles) are innervated by motor neurons in the nerve ring, (2) the next four cells in each quadrant (neck muscles) receive dual innervation from motor neurons of the nerve ring and the ventral nerve cord, and (3) the remainder (body muscles) are exclusively innervated by ventral cord motor neurons (White et al., 1986; Bird and Bird, 1991). Such innervation involves chemical synapses (NMJs) at the muscle plate. The muscle cells in each row of a muscle quadrant are electrically coupled to their neighbors through gap junctions, most often occurring between the muscle arms. Also, the muscle arms from the neck muscles make extensive gap junctions with the head mesodermal cell, which may provide electrical coupling between the dorsal and ventral muscles in this region (White, 1988). (For detailed description see Gap Junctions).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 992, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3acc6ad5-a4a7-4579-9af6-ca72e0d3b23c": {"__data__": {"id_": "3acc6ad5-a4a7-4579-9af6-ca72e0d3b23c", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Muscles, Section 5.2) Head and Neck](https://www.wormatlas.org/hermaphrodite/musclesomatic/MusSomaticframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0d9f3dd3-d7e0-498b-83f8-b55517d7b3a2", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Muscles, Section 5.2) Head and Neck](https://www.wormatlas.org/hermaphrodite/musclesomatic/MusSomaticframeset.html)"}, "hash": "d4b61d6f9e3d624929b96e56c48494c041b07fa358c5b825029e3b81fd2f81a3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Although the body is limited to making dorsoventral bends, the nematode\u00e2\u0080\u0099s head is capable of lateral motions as well. These more refined motions are believed to be due to more complex wiring of the head and neck muscles at the nerve ring, permitting differential activation of muscles in adjacent bands and even in adjacent rows in one quadrant (White et al., 1986). Head motor neuron classes include fourfold symmetric RME, SMB, and URA neurons; sixfold symmetric IL1 neurons; and bilaterally symmetric RIM, RMF, RMG, RMH, and RIV neurons (White et al., 1986). RMD and SMD motor neurons are suggested to be the cross inhibitors in the nerve ring, although the pattern of cross-inhibition is probably more complex in the head compared to the body. Both classes of putative cross-inhibitory motor neurons receive extensive synaptic input from interneurons, unlike D-type body neurons, which are only post-synaptic to ventral cord motor neurons at NMJs. The major source of synaptic input to RMD and SMD neurons comes from RIA interneurons, which themselves receive prominent input from RIB interneurons. RME neurons have been shown to limit the extent of head deflection during foraging, because head movements during foraging become loopy when RMEs are ablated (MusFIG 16) (McIntire et al., 1993; Jorgensen, 2005). RMEs are post-synaptic to stretch-receptive SMBs, and they make inhibitory NMJs onto the contralateral anterior head muscles that may have a role in restricting the level of contraction of the ventral or dorsal group of muscles during head bending (Jorgensen, 2005).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1583, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1e94776f-9d20-4c2d-8c7f-0e9aebf57b93": {"__data__": {"id_": "1e94776f-9d20-4c2d-8c7f-0e9aebf57b93", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 1) General Description](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a5e74db4-9f23-4d78-aead-b8c52707b3f9", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 1) General Description](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "hash": "ef103b3e0538334c989ace344797fb914b04bbb132a299d45e4c947151ca6a29", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Four distinctive cell types make up the excretory system: one pore cell, one duct cell, one canal cell (excretory cell), and a fused pair of gland cells (ExcFIG 1A). The nuclei of all are located in the head region, on the ventral side of the terminal bulb of pharynx and pharyngeal-intestinal valve (ExcFIG 2A). The role of the excretory cell is probably osmotic/ionic regulation and waste elimination, analogous to the renal system of higher animals. It presumably collects fluids and then empties them outside via the excretory duct and pore (Nelson and Riddle, 1984; Buechner et al., 1999). The excretory gland cells are connected to the same duct and pore, and they secrete materials from large membrane-bound vesicles. The nature of this secretion is unknown. Although excretory gland secretion may have a role in molting in other worm species, it does not seem to be essential for this function in C. elegans (Davey and Kan 1968; Nelson and Riddle, 1984). The secreted/excreted material from the canal and gland cell passes through a cuticle-lined excretory duct located just below the terminal bulb of the pharynx and is deposited outside via the pore at the ventral midline (ExcFIG 1B, ExcFIG 2B). These cells and their shapes are highly variable in nematodes (Chitwood and Chitwood, 1950).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1299, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c8d91343-49c3-4cc5-ab4b-9422add21b6f": {"__data__": {"id_": "c8d91343-49c3-4cc5-ab4b-9422add21b6f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 1) General Description](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8b751db7-1b31-4519-a16c-4d5d94bb83c3", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 1) General Description](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "hash": "e568623ee8fb527aa8963c375d786dee9c990069925651677be5572348d1f23c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The excretory system has a rather simple structure in C. elegans, except for the convoluted shape of the duct. The gland cell is suggested to receive synaptic input from the neurons in the nerve ring where its anterior process lies in close apposition to neurons (Nelson et al., 1983). Gap junctions exist between the excretory canals and the adjacent hypodermis as well as between the excretory cell and the duct cell, the excretory cell and the pore cell, and the duct and pore cells (White, 1988) (see also Gap Junctions). The excretory system is sealed by adherens junctions at several points: the origin of the excretory duct (secretory-excretory junction) where the excretory cell, gland cell and duct cell form a complex branched intercellular junction; the boundary between the duct and pore cells; the intracellular junctions formed by the pore cell wrapping onto itself around the duct; and the linkage between the pore cell and hyp7 to secure the pore opening to the bodywall (Mancuso et al., 2009). The excretory system is critical for the animal's survival, and when absent or compromised, a 'rod-like' lethal phenotype quickly results, often in early L1 stage, when the entire animal inflates with excess fluid (Li'geois et al., 2007).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1249, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "be4418d7-6830-4d77-b0f6-03161b3cf75f": {"__data__": {"id_": "be4418d7-6830-4d77-b0f6-03161b3cf75f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 2) Excretory (Canal) Cell](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e21da6b5-de8a-4aa9-8068-401339f3e305", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 2) Excretory (Canal) Cell](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "hash": "1061c9b285530307d295e72b6fee3f0386d759825cd59892591becd3636540d6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The H-shaped excretory cell (see ExcFIG 5E) is the largest cell in C. elegans and its birth at 270 minutes after first cell cleavage (just around the end of gastrulation at 22\u00c2\u00b0C) provides an easily identifiable landmark in embryogenesis (ExcFIG 3A&B) (Sulston et al., 1983; Fujita et al., 2003). Its cell body lies immediately below the anterior portion of the terminal bulb of the pharynx, adjacent to the ventral epidermal ridge, and forms a bridge between the right and left excretory canals (ExcFIG 1A&B). Its single, large nucleus, which includes a large nucleolus, is located within the cell body, just left of the midline and slightly posterior to the secretory-excretory junction (ExcFIG 2A and ExcFIG 4A). The excretory cell is polarized with distinctive basal and apical surfaces. The apical face surrounds the lumen within the canals and the excretory sinus, and the basal surface is on the outside of the cell and touches the pseudocoelom. These two faces join at the secretory-excretory junction. Laser ablation of the excretory cell, the duct cell, or the pore cell (but not the gland cell) leads to fluid collection within the animal and death within a few days, thus suggesting that these cells have a function in osmoregulation (Li\u00c3\u00a9geois et al., 2007).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1271, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d8c1c99d-58b9-43e3-86fd-c23bcee60eec": {"__data__": {"id_": "d8c1c99d-58b9-43e3-86fd-c23bcee60eec", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 2) Excretory (Canal) Cell](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "63d25a9e-26dd-412d-bdf6-43aa8fcd8dfd", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 2) Excretory (Canal) Cell](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "hash": "6952a63ec704415e3db6910b5f8541eceebdaca96f68f68e2530a2775bb377a5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The newly born excretory cell is located on the ventral side of the developing pharynx of the embryo (ExcFIG 5A). Within an hour of its birth, one or two large vacuoles appear within the cell body (ExcFIG 5B and ExcFIG 6, inset). At about the same time, the cell starts to extend two processes dorsolaterally, and this bilateral canal extension is completed by the twofold stage (~450, minutes at 22\u00c2\u00b0C) (ExcFIG 5C). The apical (lumenal) surface of the vacuole(s) is also enlarged as tubular arms grow from the initial vacuole(s) into the bilateral rudimentary canals (ExcFIG 6). A thick material that is visible by electron microscopy accumulates within the lumen (ExcFIG 6). At about the twofold stage, when they reach the lateral hypodermal ridges, the bilateral canals bifurcate to grow anterior and posterior arms located between the hypodermis and hypodermal basal lamina (ExcFIG5 D). The anterior arms run near the ventral margins of the lateral epidermal ridges, whereas the posterior arms run near the middle of them. By the time of hatching, posterior arms reach approximately the midbody, just past the V3 hypodermal seam cell. Between mid-three-fold stage and hatching, the electron-dense lumenal material disappears and an apical cytoskeletal material (terminal web) appears around the canals (Hedgecock et al., 1987; Buechner et al., 1999; Buechner, 2002; Berry et al., 2003). Simultaneously, the lumen of the canals assumes a flattened shape, and numerous canaliculi develop around the lumen to increase the apical surface area (ExcFIG 5E). The canals continue to grow actively during the first larval stage and reach their full length from the anterior tip of the organism to near the tip of the tail, just past the V6 seam cell by mid-L1. In the following three larval stages, canals grow passively with the growing length of the animal (Hedgecock et al., 1987; Buechner et al., 1999; Buechner, 2002; Berry et al., 2003). In the adult, the anterior segments of the canals are about 100 \u00ce\u00bcm in length and 1 \u00ce\u00bcm in diameter, whereas the posterior segments are about 1000 \u00ce\u00bcm in length and 2 \u00ce\u00bcm in diameter.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2122, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2e181acb-430b-4a7b-9b6e-c8e9c5b7fef1": {"__data__": {"id_": "2e181acb-430b-4a7b-9b6e-c8e9c5b7fef1", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 2) Excretory (Canal) Cell](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e7beea34-72db-45d8-b6d3-32e20033b3d8", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 2) Excretory (Canal) Cell](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "hash": "8b2ec4ba9fc796a57c80488eda8d4bd63fcd50417f91199e66760900935dcee8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The two excretory canals run along the basolateral surface of the hypodermis on each side, in close association with the processes of CAN, PVD and ALA neurons along the posterior portions (ExcFIG 7A). Among these, CAN cells have been suggested to have a role in regulating the excretory canals (Hedgecock et al., 1987). The lateral subdomain of the outer circumference of the canals is closely linked to the hypodermis by an extensive system of large gap junctions and shares a common basal lamina with it (ExcFIG 7B&C) (see also Gap Junctions). The basal subdomain of the outer circumference of each canal remains in contact with the pseudocoelom over the full length of the canal (Nelson et al., 1983). Canals contain longitudinally oriented microtubules as well as mitochondria and Golgi bodies throughout their length, whereas endosomes are concentrated at the canal endings (ExcFIG 7B&C).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 893, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1f3309a7-0535-46a3-8fa0-659ae08e0316": {"__data__": {"id_": "1f3309a7-0535-46a3-8fa0-659ae08e0316", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 2) Excretory (Canal) Cell](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "035003f8-288d-4527-a355-1ecb44fbf88f", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 2) Excretory (Canal) Cell](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "hash": "42f78100bf930d751642e0a6ba9785c405c89cb3012b77086dbf8e991a2a4f00", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The central lumen of each canal is narrower in the anterior compared with the posterior regions (Buechner, 2002). These lumena fuse and join with the origin of the excretory duct through a system of small channels termed the excretory sinus, just anterior to the cell\u00e2\u0080\u0099s nucleus (ExcFIG 8). The excretory sinus contains filamentous material that extends into the excretory duct.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 379, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "31dc94b1-ed28-44e5-9256-ce394972dcb9": {"__data__": {"id_": "31dc94b1-ed28-44e5-9256-ce394972dcb9", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 2) Excretory (Canal) Cell](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f1c76277-b681-41aa-8b92-a4b3bc58b8fd", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 2) Excretory (Canal) Cell](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "hash": "0ea6965aed265579c21b0a3b01c7607c4a269bcf3b79a14c668e606e0173839a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In a fully formed excretory cell, a system of beaded canaliculi feed into the central lumen along the length of each canal (ExcFIG 7C). These canaliculi radiate from all sides of the lumen over short lengths to fill most of the canal cytoplasm (ExcFIG 7D&E). The shape of the central lumen can vary from a collapsed tube (~1 \u00ce\u00bcm in breadth and 0.1 \u00ce\u00bcm in depth) to a round cylinder (more than 1 \u00ce\u00bcm in diameter when it is fluid-filled) (Buechner et al., 1999). The apical cytoskeleton surrounding the plasma membrane may reinforce the shape of the lumen to prevent it from deforming during fluid outflow (Buechner et al., 1999). The shapes of the canaliculi are more plastic, and under different conditions, the canaliculi may variably appear as smooth, narrow tubes or as a set of connected beads (50 nm beads connected by narrow necks); they can also break up into a set of larger (90 nm) vesicles that are disconnected from their neighbors and from the lumen. Recent studies using electron tomography to follow the adult canal in three dimensions show that the canaliculi are actually not beads on a linear 'string', but form short branched networks, with the stem of each branch attaching to the lumen (Zhang et al., 2012 and unpublished data) (ExcFIG 7D&E). Most canaliculi (beads) lie within 1-4 bead-length from their lumenal connection.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1344, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0a0e9ddc-c28a-41f5-9e66-d691ec2a8cf8": {"__data__": {"id_": "0a0e9ddc-c28a-41f5-9e66-d691ec2a8cf8", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 2) Excretory (Canal) Cell](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "477292dd-c68c-4779-985d-71adc9e1ba94", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 2) Excretory (Canal) Cell](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "hash": "9776f8701d88766e4ccb25e0039b85e9868dbf3517c697bac7723dd772a9a7ba", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Both the central canal and canaliculi are lined by lumenal glycocalyx (mucin) that is essential for effective functioning of the secretory/excretory system (Jones and Baillie, 1995). A distinct set of mutations (\u00e2\u0080\u009cexc\u00e2\u0080\u009d: excretory canal defective) in genes expressed in the excretory cells is known to cause tubular pathologies in the form of gross cyst formation along the canal lumen, ranging from focal cysts, followed by normal-width segments, to large cysts involving almost the entire tubule (Buechner et al., 1999; Gao et al., 2001; Suzuki et al., 2001; Fujita et al., 2003). Some of these genes encode structural proteins such as SMA-1 (spectrin), necessary to reinforce the apical membrane on the cytoplasmic side, lumenal molecules such as mucin (LET-653) or ion channels (Jones and Baillie, 1995; McKeown et al., 1998; Berry et al., 2003).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 852, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b433f944-dfab-4927-9e24-20fa5e12c52c": {"__data__": {"id_": "b433f944-dfab-4927-9e24-20fa5e12c52c", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 2) Excretory (Canal) Cell](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e949ea5e-ea7c-45c9-a469-33d2ae132cd2", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 2) Excretory (Canal) Cell](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "hash": "bc9ababdf4147de46af5b3c44d9b2ac208f28fb513cb2fa7c17e4761afc44787", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Several proteins in the plasma membrane, lumenal membrane, or canaliculi have been implicated in the excretory canal cell's important physiological role in osmoregulation, including an aquaporin (AQP-8), a chloride channel (CLH-3), several anion transporters (ABTS-2, SULP-4, SULP-5), a receptor-mediated cation export channel (GTL-2) and many vacuolar ATPases (VHA-1, 2, 4, 5, 8,11,12,13,15, 16 and VHA-17) (Li'geois et al., 2007; Hisamoto et al., 2008; Mah et al., 2007; Sherman et al., 2005; Teramoto et al., 2010; Hahn-Windgassen and Van Gilst, 2009).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 555, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "68c8fd8e-e17a-4da7-8e6f-a72daa0437fe": {"__data__": {"id_": "68c8fd8e-e17a-4da7-8e6f-a72daa0437fe", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 3) Excretory Gland Cell](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "466d47f2-8fa3-45ff-a3a0-a5c38f80c7cf", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 3) Excretory Gland Cell](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "hash": "f70bf1120b3b1aeb3a6bede8ff60a2e3b0110223469175f8d7bd604eeeefbed5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The excretory gland is a binucleate, A-shaped cell that is formed by fusion of two identical (exc gl L and R) cells (ExcFIG 3C; ExcMOVIE 1) (Nelson et al., 1983). It has two separate cell bodies lying subventrally in the pseudocoelomic space, on the left and right sides and just posterior to the pharyngeal-intestinal valve (ExcFIG 4B). A large process from each cell body projects anteriorly along the dorsal surface of the ventral nerve cord and fuses with the other side at the level of the secretory-excretory junction, across the anterior edge of the excretory cell body (ExcFIG 8). The bilateral gland cell processes separate again anterior to this bridge region and fuse a second time near their anterior limit to form a ring-like process which projects into the nerve ring. The gland cell is suggested to receive synaptic input from nerve ring neurons in this region (Nelson et al., 1983).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 898, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0d018db3-a9bb-4baf-8960-336fd08bbe7e": {"__data__": {"id_": "0d018db3-a9bb-4baf-8960-336fd08bbe7e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 3) Excretory Gland Cell](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f6a424f2-32d4-4419-8fb2-c26bc2528a12", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 3) Excretory Gland Cell](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "hash": "acf4a615d82902715453e4ce7d000066b8853d1a5255cb31ab9060cbcc988a88", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The gland cell cytoplasm contains an extensive network of dilated cisternae of rough endoplasmic reticulum, many mitochondria and ribosomes, Golgi complexes, and clusters of electron dense secretory granules (Nelson et al., 1983). These granules are concentrated around the cytoplasmic bridge region near the secretory membrane, which is a specialized portion of the cell membrane that connects to the origin of the excretory duct (ExcFIG 8). Any glandular secretions entering the duct may conceivably reach the excretory sinus through the secretory-excretory junction. As the animal grows the gland cell enlarges in proportion to the size of the animal,  and the number of secretory granules increases, although the changes are not synchronous with the molting cycle (Nelson et al., 1983). The vesicles become less electron-dense in the adult gland. In dauer larvae, the gland cell cytoplasm contains only a loose membraneous network and no secretory granules. This does not seem to be a result of starvation but rather is related to this developmental state itself. The function of excretory gland cell is currently unknown. It does not seem to be involved in molting in C. elegans (Singh and Sulston, 1978), and ablation of the gland cell does not result in any obvious defects (Nelson and Riddle, 1984).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1307, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "aeddae70-ffcf-4cb8-91f5-1542fccea4ed": {"__data__": {"id_": "aeddae70-ffcf-4cb8-91f5-1542fccea4ed", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 4) Duct Cell](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fb3386ed-76bb-41f0-b94c-4e8bf26c1190", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 4) Duct Cell](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "hash": "2c5721dd87ed5393e749405a6ecef256c2052b37e9c2debbd7225840dbe4c387", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The excretory duct of C. elegans is a 15 \u00ce\u00bcm long, cuticle-lined channel that connects the excretory system to outside via the excretory pore located at midline on the ventral side of the body. The duct cell surrounds the duct from its origin to the boundary of the pore cell, covering about two thirds (9-10 \u00ce\u00bcm) of the duct, which follows a looped path within the cell (ExcFIG 1A&B). The duct cell is located just anterior and lateral (left or right) to the excretory cell body, and hence, the initial portion of the duct can be located either to the right or the left of the excretory cell (Nelson et al., 1983). The morphology of the duct cell, as well as the placement of the duct and pore along the anterior-posterior axis within related Caenorhabditis species seems to be determined by the zinc-finger gene lin-48 (Wang and Chamberlin, 2002; 2004).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 855, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fbc070bc-5dbb-4773-bf73-73a3e8142582": {"__data__": {"id_": "fbc070bc-5dbb-4773-bf73-73a3e8142582", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 4) Duct Cell](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d2d35bba-59aa-4d48-bb3f-7b05d8d7d9ed", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 4) Duct Cell](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "hash": "83202acb61b45a467fa94e28255f3eb8d4831228e0688c4fc26e2bc4ec95c62a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Inside the duct cell, the plasma membrane surrounding the duct invaginates extensively, creating lamellar stacks which greatly increase the surface area of the membrane (ExcFIG 4A and ExcFIG 9C). These lamellar sheets become more elaborate as the animal matures and are similar to those seen in hypodermis (White, 1988). Laser ablation of the duct cell leads to absence of cuticle within the duct cell portion of the excretory duct after a molt, suggesting duct cell integrity is required for formation of cuticle lining within the duct cell environment (Nelson and Riddle, 1984).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 580, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "20a2eb27-0b76-41ec-bdcf-549d2cd4e59f": {"__data__": {"id_": "20a2eb27-0b76-41ec-bdcf-549d2cd4e59f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 4) Duct Cell](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3407540c-f155-4b60-b069-74743ec8b21e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 4) Duct Cell](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "hash": "b75d39a460cf4edf6888f8676647809b2ca7159eb3d51097cac4b7192d9e4a1a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Mutations that slow the growth of the duct cell lumen during embryogenesis can lead to rod-like lethality if the lumen breaks down anywhere along the length of the duct (Stone et al., 2009). In addition, as with the excretory cell, duct cell ablation eventually causes fluid accumulation within the animal followed by death, suggesting a function in osmotic/ionic regulation. This function is also supported by the finding that In other nematode species the pulse rate of the duct changes according to the osmolarity of the environment.\u00a0 However, in C. elegans, the only stage when any duct pulsation is observed is the dauer larva (See Dauer Cuticle) (Nelson and Riddle, 1984).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 678, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "dd48c3d8-0cec-412b-9c32-3b6cfe97ddf9": {"__data__": {"id_": "dd48c3d8-0cec-412b-9c32-3b6cfe97ddf9", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 5) Pore (excretory socket) Cell](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "785c281c-6063-43c3-947e-21edef4e8fe0", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 5) Pore (excretory socket) Cell](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "hash": "a43b91e1148678ac9d9b9e86fe6aa09e277eb6b778a62c201efb10b32968c258", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Like the duct cell, the pore cell is a specialized, transitional, epithelial cell. It encloses the ventral third of the duct and forms an adherens junctions with the duct cell at the duct cell-pore cell junction. It also makes junctions with itself by wrapping around the duct (Nelson et al., 1983). The pore cell underlies the excretory pore on the ventral side of the animal where the duct wall cuticle becomes continuous with the body wall cuticle (ExcFIG 9A). Around this region, the pore cell makes adherens junctions to the surrounding hypodermis and seals the pore (ExcFIG 9B). In the embryo, the G1 cell acts as the excretory pore cell (excretory socket cell). After hatching, G1 becomes a neuroblast and the pore function is taken over by G2 (ExcFIG 10). Eventually at L2 stage, G2 divides and the posterior daughter of G2 (G2.p) becomes the mature excretory pore cell, while the anterior daughter (G2.a) becomes a neuroblast (Nelson et al., 1983, Sulston, 1983). Mutations that inhibit this pore cell swap, or inhibit the remodeling of adherens junctions between the duct cell and the new pore cell can cause rod-like lethality if the duct/pore junction is lost (Abdus-Saboor et al., 2011; Mancuso et al., 2012).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1222, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2fd91c6d-ea02-4018-b45f-3e02d818a4f2": {"__data__": {"id_": "2fd91c6d-ea02-4018-b45f-3e02d818a4f2", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 5) Pore (excretory socket) Cell](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c0f90ab2-55e7-4446-a4ca-89d4a8f74586", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 5) Pore (excretory socket) Cell](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "hash": "601c81b9920c4e9f91d89b4faed06d84fc17820629a3b776baee1534c8f83919", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The duct cell and pore cell share responsibility for secreting the new duct cuticle at each molt. In animals where the pore cell is ablated, cuticle is completely absent throughout the duct (Nelson and Riddle, 1984). The excretory pore remains open throughout all developmental stages including the dauer larva (See Dauer Cuticle).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 331, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e2386a0b-d229-47d3-ba3e-8d11545534ac": {"__data__": {"id_": "e2386a0b-d229-47d3-ba3e-8d11545534ac", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 6) List of Cells of the Excretory System](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bf2db80f-5e03-459c-8928-b8c6f95cb7c1", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 6) List of Cells of the Excretory System](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "hash": "f8bb1b528cbf3915fc5b74a185e4f04241b0f003e61bde45226c5bea29afa177", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Excretory canal cell (exc cell)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 31, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3364e70b-a760-46c6-a4f3-249c91ea950c": {"__data__": {"id_": "3364e70b-a760-46c6-a4f3-249c91ea950c", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 6) List of Cells of the Excretory System](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "43dfbb3b-b359-47d5-b16f-4fe07ac05890", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 6) List of Cells of the Excretory System](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "hash": "22d41b262fbda72755d5e0013985e23b6fabe3167269818ef889ec347c89528b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Excretory gland cell (syncytial)\n\nExc gl L\n\nExc gl R", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 52, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "51f4040a-f47b-4d13-a76e-ea2b747c3093": {"__data__": {"id_": "51f4040a-f47b-4d13-a76e-ea2b747c3093", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 6) List of Cells of the Excretory System](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "eff6fdbd-6a0a-46a5-8cda-d0622a1f23ce", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 6) List of Cells of the Excretory System](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "hash": "4bc91f77fe66cf4bc13fe3f9a9babe7ec4cf90ef93d6425568dc812c4348706c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Excretory duct cell", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 19, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "543c19f3-99b2-4e5f-9223-10fca98d36ed": {"__data__": {"id_": "543c19f3-99b2-4e5f-9223-10fca98d36ed", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 6) List of Cells of the Excretory System](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3a986e44-c2f4-4396-a15a-d5a564f4d8db", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 6) List of Cells of the Excretory System](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "hash": "85b946be54eb80098834bb79a9b21216dc7629f6d8d3eeb1024cd0fb66c95eb5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Excretory pore cell:\n\nG1 (only at embryo stage)\n\nG2 (only at L1 stage)\n\nExc pore cell [aka excretory socket cell] (L2 and later stages)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 135, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c3d8e2c0-9245-4765-8bc0-5105805244d9": {"__data__": {"id_": "c3d8e2c0-9245-4765-8bc0-5105805244d9", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 6) List of Cells of the Excretory System](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "af281c0a-2532-481b-9bd9-698cddd6211a", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Excretory System, Section 6) List of Cells of the Excretory System](https://www.wormatlas.org/hermaphrodite/excretory/Excframeset.html)"}, "hash": "7f7eaabb6d7de8d1c6e0aef5e8323c3c06d19badda04dbd26ede74319e22cf17", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "More figures of the excretory system", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 36, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f1d6b551-1d47-4dfd-b050-81015ec034f2": {"__data__": {"id_": "f1d6b551-1d47-4dfd-b050-81015ec034f2", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Interfacial epithelial cells, Section 1) Overview](https://www.wormatlas.orghermaphrodite/interfacial/Interframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7050bd74-777b-44e8-8190-d13345187a51", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Interfacial epithelial cells, Section 1) Overview](https://www.wormatlas.orghermaphrodite/interfacial/Interframeset.html)"}, "hash": "f9c1b496a07377643d01799b15eb9e821b2c8585d36363534782fe77a253b978", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Interfacial epithelial cells are located at the interface between the hypodermis and another type of tissue, at the points where these tissues attach to the hypodermis or open to outside through holes in the hypodermis. They are often intermediate in function and morphology between hypodermis and these adjacent tissues. They arrange in toroidal conformations that surround the junction site. All have epithelial characteristics and some secrete cuticle, forming smooth transitions between cuticles with different compositions (White, 1988). Interfacial epithelial cells include arcade cells and the pharyngeal epithelium of the buccal cavity, the vulval epithelium at the vulval opening, the rectal epithelium at the rectal canal and anus (proctodeum), socket and sheath cells (glia) at sensory openings, and the duct cell and pore cell forming the excretory pore. Detailed discussions of these cells, except for the arcades, are provided in chapters regarding the alimentary system (pharyngeal epithelium and rectal epithelium), the reproductive system (vulval epithelium), the nervous system (glia) and the excretory system (the duct and pore cells). In males, rectal epithelial cells generate the cloacal-gonadal connection (see Proctodeum), instead of rectal canal and anus (see also Male Anatomy).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1304, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "37ad2406-d279-4961-ae4f-fa0cb6167523": {"__data__": {"id_": "37ad2406-d279-4961-ae4f-fa0cb6167523", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Interfacial epithelial cells, Section 2) Arcade Cells](https://www.wormatlas.orghermaphrodite/interfacial/Interframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "83f7cbce-cde2-4454-90e1-20cc603cf47f", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Interfacial epithelial cells, Section 2) Arcade Cells](https://www.wormatlas.orghermaphrodite/interfacial/Interframeset.html)"}, "hash": "03d970bfa5870e1f42ab44492e126a54454d0584cb0648a41951eff9ac488c29", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The anterior hypodermis consists of three specialized rings of cells (hyp1, hyp2, hyp3; cheilostom) (see HypFIG 10) that outline the anteriormost edge of the bodywall at the mouth and lips. The anterior end of the pharynx consists of an interfacial cell group known as the pharyngeal epithelium. Spanning the gap between hyp1 and the pharyngeal epithelium are the arcade cells (InterFIG 1) (Mango, 2007). Together, arcade cells and the pharyngeal epithelium form the buccal cavity and link the digestive tract to the outside and to body hypodermis.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 548, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ce117523-54be-4673-9d6c-ac81e7a28235": {"__data__": {"id_": "ce117523-54be-4673-9d6c-ac81e7a28235", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Interfacial epithelial cells, Section 2) Arcade Cells](https://www.wormatlas.orghermaphrodite/interfacial/Interframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "86643afb-632c-40d1-97e7-f2bb42efc68e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Interfacial epithelial cells, Section 2) Arcade Cells](https://www.wormatlas.orghermaphrodite/interfacial/Interframeset.html)"}, "hash": "9438b8accc6f2a27981b7caa1d95e9dc00cb4012454325a9f6f117a69e401c0d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "There are nine arcade cells that organize into two separate epithelial syncytia: the anterior arcade and the posterior arcade (InterFIG 2, InterMOVIE 1). Each of these syncytia has a cytoplasmic ring that surrounds the anterior of the buccal cavity (InterFIG 3). Their cell bodies, which are located in the body wall more posteriorly and close to the anterior bulb of pharynx, are connected to these rings by thin cytoplasmic processes (InterFIG 2 and InterFIG 4). Similar to other precursor cells of the buccal cavity, the arcade cells move inwards from their ventral position during embryogenesis, generating these processes (Wright and Thomson, 1981). In some cases cell fusion also occurs between these processes before reaching the syncytial ring. The anterior arcade ring is generated by the fusion of processes from three cells (arc ant DL, arc ant DR and arc ant V), whereas the posterior arcade ring is formed by the fusion of processes extended from six cells (arc post D, arc post DL, arc post DR, arc post V, arc post VL and arc post VR) (Wright and Thomson, 1981).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1077, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "bb8f814b-db26-4c98-83e8-4b88139e3233": {"__data__": {"id_": "bb8f814b-db26-4c98-83e8-4b88139e3233", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Interfacial epithelial cells, Section 2) Arcade Cells](https://www.wormatlas.orghermaphrodite/interfacial/Interframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "129bab14-29e7-4304-9b4d-60fe835cbeaf", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Interfacial epithelial cells, Section 2) Arcade Cells](https://www.wormatlas.orghermaphrodite/interfacial/Interframeset.html)"}, "hash": "30b017a167907ddb7eaf5e3c4054e6b326d8be6fead7b5b1470b270652032ea4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The two arcade rings are firmly sealed to each other and to neighboring tissues via adherens junctions. The adherens junctions between the posterior arcade and the most anterior ring of pharyngeal epithelium are very robust and form one continuous belt desmosome along the entire border. The adherens junctions linking the two rings of arcade cells and the anterior arcade to the ring of hyp 1 syncytium are less robust. Preliminary evidence suggests that there are also gap junctions between these cells. Although not yet confirmed by examination at higher magnification, it appears that gap junctions link the two arcade rings to each other, and also possibly link the arcades to hyp 1 and to the anteriormost pharyngeal epithelial cells (D.H. Hall, unpublished).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 765, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b4b36e5a-edb7-4a3a-9126-4a044ba2a001": {"__data__": {"id_": "b4b36e5a-edb7-4a3a-9126-4a044ba2a001", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Interfacial epithelial cells, Section 2) Arcade Cells](https://www.wormatlas.orghermaphrodite/interfacial/Interframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c55fda7c-a728-43cd-9f58-af7b57ae890f", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Interfacial epithelial cells, Section 2) Arcade Cells](https://www.wormatlas.orghermaphrodite/interfacial/Interframeset.html)"}, "hash": "2afb5e13e4381587aad485332fb4dbfe62b1c38172dfe8d1448955a52e46c9ff", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The arcade cell cytoplasm generally appears quite clear (electron lucent) compared to other epithelia, except for the portion closest to the buccal cavity, which often shows increased density at the plasma membrane. The arcade cells contain many free ribosomes and mitochondria, but very little endoplasmic reticulum (ER). Just prior to the molts, the arcade cells become filled with dense core vesicles that cluster near the cuticle, which suggests that the arcade cells build new cuticle by vesicle secretion (Wright and Thomson, 1981; D.H. Hall, unpublished; see Cuticle).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 575, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "678eaa10-e8f2-499b-b0cb-93d1dfd358b9": {"__data__": {"id_": "678eaa10-e8f2-499b-b0cb-93d1dfd358b9", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Interfacial epithelial cells, Section 3) Buccal Cavity](https://www.wormatlas.orghermaphrodite/interfacial/Interframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3ff6416a-6f22-46ca-9283-8fc1a38c521e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Interfacial epithelial cells, Section 3) Buccal Cavity](https://www.wormatlas.orghermaphrodite/interfacial/Interframeset.html)"}, "hash": "96c8e9da07d0c58d1f0c83a815ec99dfd24d8d23cc663d0f15ca09445437a6b2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The nematode digestive system consists of three parts: the stomodeum, intestine and proctodeum (rectum and anus). Embryologically, the stomodeum and proctodeum have a mixed lineage derived from cells of both ectodermal and mesodermal origin, whereas intestine (gut) is wholly endodermal in origin. Stomodeum includes the mouth and the lips, the buccal cavity (stoma), and the pharynx (esophagus) (see Alimentary  System for detailed descriptions of the pharynx, intestine, rectum and proctodeum).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 496, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "26dd55ed-cddd-42f7-ad42-2df61c49aa81": {"__data__": {"id_": "26dd55ed-cddd-42f7-ad42-2df61c49aa81", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Interfacial epithelial cells, Section 3) Buccal Cavity](https://www.wormatlas.orghermaphrodite/interfacial/Interframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "66225dd7-e00d-47bd-891c-3f20f73d9ae5", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Interfacial epithelial cells, Section 3) Buccal Cavity](https://www.wormatlas.orghermaphrodite/interfacial/Interframeset.html)"}, "hash": "e9b3c82fd33247b01838640a9be966c18e30e3635c8d60c085169deaed0214e1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Rhabditids that feed on bacteria, such as C. elegans, have a relatively narrow and cylindrical, smoothly lined buccal cavity. In earlier literature this buccal cavity had been described as divided into five regions: cheilostom, prostom, mesostom, metastom and telostom, from anterior to posterior (Bird and Bird, 1991). More recently, however, throughout the class Secernentea, including Rhabditida, the cuticle-lined lumen of the buccal capsule has been subdivided from anterior to posterior into three chambers: the cheilostom, gymnostom, and stegostom (InterFIG 1B) (De Ley et al., 1995). Cheilostom is surrounded by hypodermis, gymnostom (former prostom) is surrounded by the pair of arcade syncytia, and stegostom (former mesostom, metastom and telostom) is surrounded by a longitudinal series of four sets of radial pharyngeal cells (e1, e3, pm1, pm2; see Alimentary System - Pharnyx) (Dolinski et al., 1998).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 915, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c7189583-c68c-4c45-a391-3b129e482a51": {"__data__": {"id_": "c7189583-c68c-4c45-a391-3b129e482a51", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Interfacial epithelial cells, Section 3) Buccal Cavity](https://www.wormatlas.orghermaphrodite/interfacial/Interframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "93c96d05-2732-4681-be75-2a9849c0ed2d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Interfacial epithelial cells, Section 3) Buccal Cavity](https://www.wormatlas.orghermaphrodite/interfacial/Interframeset.html)"}, "hash": "eb7a9437da14665ebb2532d46ad939e10d1d73cae756186fef2a1212c028c147", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In rhabditid nematodes, the specialized cuticular zones that line the mouth and the buccal passage have the suffix \"rhabdia\" (Bird and Bird, 1991). Hence, cheilorhabdion and prorhabdion refer to the cuticular coverings of the lips, and arcade regions, respectively, whereas mesorhabdion, metarhabdion and telorhabdion refer to the cuticular lining of the posterior buccal regions. Where the arcade tissue bridges the gap between hypodermal tissue and pharyngeal epithelium, the arcade cells also secrete a narrow ring of cuticle that seals the body cuticle of the lips to the buccal cuticle via a local, notched joint known as the cheilostom groove (InterFIG 1) (Wright, 1976, Wright and Thomson, 1981). Although, the cuticles of the body and buccal capsule are distinct in C. elegans, the cuticles of the different regions of the capsule are similar. Since body cuticle does not enter the buccal cavity, C. elegans is categorized as an \u00e2\u0080\u009castomatous\u00e2\u0080\u009d species (Wright, 1976; Wright and Thomson, 1981). During molts, the cuticular linings of the buccal capsule and the pharynx are also shed. The body cuticle undergoes apolysis and a new cuticle is laid down before the apolysis of the buccal capsule cuticle and pharyngeal cuticle. Unlike body cuticle, pharyngeal cuticle and buccal capsule cuticle are broken down following apolysis. (Wright and Thomson, 1981; see Cuticle).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1377, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7707726c-31fe-41c7-81d8-d22e04a06479": {"__data__": {"id_": "7707726c-31fe-41c7-81d8-d22e04a06479", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Interfacial epithelial cells, Section 4) Development of the Buccal Cavity and the Anterior Foregut](https://www.wormatlas.orghermaphrodite/interfacial/Interframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "721800c4-05d9-4403-8798-46944f442220", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Interfacial epithelial cells, Section 4) Development of the Buccal Cavity and the Anterior Foregut](https://www.wormatlas.orghermaphrodite/interfacial/Interframeset.html)"}, "hash": "2b81aebe09b193f2fcf41f8a57abfc1a3e2961eab85c36868f4f6bbacf2cf731", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The morphogenesis of the pharynx starts at the late comma stage, after gastrulation is complete and approximately 330 minutes after first cell division. At this stage, 78 of the 80 pharyngeal cells have been born and the pharyngeal primordium has formed a cystic ball inside the embryo (InterFIG 5). This compact tissue borders the nascent intestine at the posterior and is connected to it by adherens junctions, but is not yet connected to the buccal cavity. The hypodermal and nine arcade cells fill the 11- to 12-\u00ce\u00bcm space between the pharyngeal cells and the anterior of the embryo. Over the next 60 minutes, the pharyngeal cells go through a process called \u00e2\u0080\u009cpharyngeal extension,\u00e2\u0080\u009d when they convert from a cyst to a short, linear tube that links the digestive tract to the buccal cavity (InterFIG 5 and InterFIG 6) (Portereiko and Mango, 2001; Mango, 2007). Pharyngeal extension takes place through coordinate formation of new epithelia without any cell migrations and has three stages: reorientation of pharyngeal epithelial cells, epithelization of the arcade cells, which are originally mesenchymal, and contraction of the buccal cavity and the pharyngeal epithelial cells. During the first stage, pharyngeal epithelial cells rotate and reorient their apicobasal polarity along the dorsoventral axis from the rostrocaudal axis. This rearrangement aligns the pharyngeal epithelial cells of the anterior edge of the pharyngeal primordium with the arcade cells. During the second stage, the arcade cells form adherens junctions with the pharyngeal epithelium and the hypodermis, generating a continuous epithelium between the hypodermis and the anterior pharynx. The arcade cell epithelium is the last epithelium to form in the embryo, and its formation takes place in less than 10 minutes (Portereiko et al., 2004). In the last stage, contraction of the apical surface of this continuous epithelium pulls the cells together, moving the hypodermis backward while moving the pharynx forward (Portereiko and Mango, 2001). During later embryogenesis, the linear pharyngeal tube that forms at the end of pharyngeal extension develops a lumen and undergoes an extensive morphogenetic program to produce the characteristic two-lobed structure of the fully differentiated pharynx (see Alimentary System - Pharynx).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2316, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3891a42f-9142-45e9-bb3a-2c9bb3365b33": {"__data__": {"id_": "3891a42f-9142-45e9-bb3a-2c9bb3365b33", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Interfacial epithelial cells, Section 5) List of Interfacial Epithelial Cells](https://www.wormatlas.orghermaphrodite/interfacial/Interframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "abc035c6-bab5-4b89-ab50-d848943fa2cf", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Interfacial epithelial cells, Section 5) List of Interfacial Epithelial Cells](https://www.wormatlas.orghermaphrodite/interfacial/Interframeset.html)"}, "hash": "b1d305484e6f87d8a96b15658dbe083f31bab0d00f30e0a1afe0ecbb848a0f05", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "5. Glia \n\n (see Neuronal Support Cells)\n\nADEshL\n\nADEshR\n\nAMshL\n\nAMshR\n\nCEPshDL\n\nCEPshDR\n\nCEPshVL\n\nCEPshVR\n\nILshDL\n\nILshDR\n\nILshL\n\nILshR\n\nILshVL\n\nILshVR\n\nOLLshL\n\nOLLshR\n\nOLQshDL\n\nOLQshDR\n\nOLQshVL\n\nOLQshVR\n\nPDEshL\n\nPDEshR\n\nPHshL\n\nPHshR\n\nADEsoL\n\nADEsoR\n\nAMsoL\n\nAMsoR\n\nCEPsoDL\n\nCEPsoDR\n\nCEPsoVL\n\nCEPsoVR\n\nILsoDL\n\nILsoDR\n\nILsoL\n\nILsoR\n\nILsoVL\n\nILsoVR", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 345, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "47c8fe28-cbb8-4ab0-8859-bae2c8771552": {"__data__": {"id_": "47c8fe28-cbb8-4ab0-8859-bae2c8771552", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 1) General Description](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0e08c4a2-3b34-4d33-a060-afd0465a9bef", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 1) General Description](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "hash": "1531268a3c524ac20bafed32ed391cfdc8eb29e240bf7307943c507ac574d4e7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The somatic gonad refers to the non-germ-line component of each arm (SomaticFIG 1). It consists of five tissues, each with specific functions and distinct anatomical features: the DTCs, gonadal sheath, spermatheca, spermatheca-uterine valve, and the uterus (covered in Reproductive System - Egg-laying Apparatus ). These tissues, in particular the sheath and DTC, are intimately associated with the germ line and have a critical role in its development, organization, and function in the adult (Kimble and White, 1981; McCarter et al., 1997; Hall et al., 1999). All cells of the somatic gonad derive from two founder cells Z1 and Z4 that are present in the L1 gonad primordium (SomaticFIG 1). By L2, Z1/Z4 have generated 12 descendants: two DTCs, required for gonad elongation and germ-line patterning; nine blast cells that will, collectively, generate all other adult somatic gonad cells; and one anchor cell (AC), a transient cell that functions to pattern the cells of the vulva. Somatic and germ cells are intermingled until the L2/L3 molt, at which time they rearrange to establish the general organization of the future gonad (SomaticFIG 1). The DTCs are positioned at the anterior and posterior of the developing gonad. The ten remaining cells gather at the center to form the somatic gonadal primordium of the hermaphrodite (SPh), thus dividing the germ line into anterior and posterior populations of cells or arms (Kimble and Hirsh, 1979).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1450, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c1f84c30-5074-4f0f-a0e1-4c1f9e8d2337": {"__data__": {"id_": "c1f84c30-5074-4f0f-a0e1-4c1f9e8d2337", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 2) The Distal Tip Cell](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f509c4d1-90cf-4793-892a-8e3ba40682c1", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 2) The Distal Tip Cell](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "hash": "731d38593fae6f752977591c6ae90df64ce08863d60f1643b9f123c509c44466", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The DTC is a single, large somatic cell located at the tip of each gonad arm. It forms a close-fitting cap over the distalmost 6\u00e2\u0080\u009310 germ cells. No intervening basement membrane or specialized intercellular junctions are found between the DTC and germ cells. Several thin cytoplasmic arms (tentacle-like cytonemes), less tightly associated with germ cells, extend from the cap for an average of 8 \u00c2\u00b1 4 cell diameters (but can extend as far as 20 cell diameters; SomaticFIG 2A,B). The gonadal basal lamina (GBL), which covers the entire outer surface of the gonad, is thickened in the region of the DTC (SomaticFIG 2C). Fragments of the GBL appear to be shed from the trailing arms of the DTC into the pseudocoelom. The DTC has a large nucleus located at its leading (distal) edge and its cytoplasm is filled with distinctive membrane-bounded vacuoles, some rough endoplasmic reticulum (RER), and mitochondria. The plasma membrane sometimes displays \u00e2\u0080\u009comega\u00e2\u0080\u009d figures (see SomaticFIG 2E) where it faces the GBL, indicative of active endocytosis or exocytosis. The gross anatomy of the DTC cell, born in the L1, does not alter significantly during the course of development, although the adult cell appears to contain more and longer cytonemes extending over the germ line (D.H. Hall and E.M.  Hedgecock, unpubl.).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1315, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "20506eba-4e4a-4b48-8a02-5ee38bca75e3": {"__data__": {"id_": "20506eba-4e4a-4b48-8a02-5ee38bca75e3", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 2) The Distal Tip Cell](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9fac4255-7cec-4b8e-addf-0fe5c17206d2", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 2) The Distal Tip Cell](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "hash": "ee0b4c1085b3d45ee15aa47a6bd9a470068d280503bbe895cb3c151749caae87", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The hermaphrodite DTC has two major functions: (1) gonadal arm elongation during development and (2) promoting mitosis and/or inhibiting meiosis of the germ cells, both during development and in the adult.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 205, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b971cefe-1682-437c-95da-cdd17e33fbc8": {"__data__": {"id_": "b971cefe-1682-437c-95da-cdd17e33fbc8", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 2) The Distal Tip Cell](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "872418c0-a479-43c6-84a3-0bafd68750ac", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 2) The Distal Tip Cell](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "hash": "2334f57469e513b07e51280da76e0e4b4baeda8009d32a8ca9ae37f10ecebfde", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "2.1 Gonadal Arm Elongation", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 26, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "895353ee-728d-42d0-9935-8d0c9c9cee14": {"__data__": {"id_": "895353ee-728d-42d0-9935-8d0c9c9cee14", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 2.1) Gonadal Arm Elongation](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3fd00b12-1472-4063-a9cd-62b49ff6b735", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 2.1) Gonadal Arm Elongation](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "hash": "91bc167843f04bbafdf577526a13157514b63ac3a32997fd045070de65f4f378", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The gonad arms acquire their U shape by the directed migration of the DTC, which acts as a leader cell (SomaticFIG 3A\u00e2\u0080\u0093D). Arm elongation begins in L2 (21 hr, 20\u00c2\u00b0C) and continues, proceeding at variable rates, until the L4 molt (45 hr) (Antebi et al., 1997; D.H. Hall and E.M. Hedgecock, unpubl.). During migration, the DTC glides along the basal laminae of body wall muscles and hypodermis. The DTC produces a metalloprotease (GON-1) that is hypothesized to facilitate migration by remodeling the basal laminae during gonad extension (Blelloch and Kimble, 1999; Blelloch et al., 1999). In contrast to neuronal growth cones, the leading edge of the DTC is broad and blunt during migration and bears no fingers or lamellipodia (SomaticFIG 2). Genetic functions that control elongation include global guidance molecules (such as unc-6, unc-5, and unc-40) (Hedgecock et al., 1987; 1990) and cell recognition functions such as those defined by the programmed cell death corpse engulfment genes (e.g., ced-2, ced-5, and ced-10) (Conradt, 2001). DTC migration also appears to be sensitive to global signals of the developmental stage because migration halts during dauer arrest and is advanced or delayed in heterochronic mutant backgrounds (Ambros, 1997; Antebi et al., 1997).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1273, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2f4c38cd-5b09-4c98-a8fa-35b1d753724a": {"__data__": {"id_": "2f4c38cd-5b09-4c98-a8fa-35b1d753724a", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 2.2) Regulation of Germ-line Mitosis Versus Meiosis Entry](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a9561d3b-1822-42ed-99ea-cf91bea5c13a", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 2.2) Regulation of Germ-line Mitosis Versus Meiosis Entry](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "hash": "a8cb2aa5e863b382c06b5b89e0c71a31c77d2bc77f3d8e024e5bdf5ab502aabe", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The adult germ line exhibits distal\u00e2\u0080\u0093proximal polarity with mitotic cells at the distalmost end and meiotic cells filling the remainder of the gonad (SomaticFIG 4). Ablation of the DTC causes all mitotic nuclei to become meiotic and all meiotic nuclei to mature into gametes, the fate of the proximalmost meiotic germ cells (Kimble and White, 1981; Austin and Kimble, 1987; Lambie and Kimble, 1991). The DTC regulates entry into mitosis versus meiosis through a Notch/LIN-12 signal transduction pathway (Lambie and Kimble, 1991; Crittenden et al., 1994; Henderson et al., 1994; Tax et al., 1994). The DTC expresses the pathway ligand LAG-2 (Lin and Glp), whereas the germ line expresses the pathway receptor GLP-1 (germ-line proliferation abnormal mutant phenotype) and downstream effectors (SomaticFIG 2 and SomaticFIG 4B). Pathway activation blocks entry into meiosis (or promotes mitosis), maintaining germ cells near the DTC in a mitotic state (Hansen et al., 2004). It is hypothesized that germ cells enter meiosis by default due to their increased distance from the DTC. During development, the exact position and timing of the initial onset of meiosis at L3 is influenced by both DTC and non-DTC somatic cells (see GermFIG 6) (Pepper et al., 2003; Killian and Hubbard, 2004). Much of the DTC\u00e2\u0080\u0093germ-line contact region falls short of the mitotic zone proximal boundary (SomaticFIG 4), suggesting that pathway activation must be propagated in some way to explain how cells that are not in direct contact with DTC stay in a mitotic state (see PeriFIG 3) (for models, see Crittenden et al., 1994; 2003).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1608, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "897edb3b-c451-4a41-b0c9-6cf969d17fde": {"__data__": {"id_": "897edb3b-c451-4a41-b0c9-6cf969d17fde", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 3) Gonadal Sheath Cells](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "16ced102-199a-4abf-b1fd-2ce3b632dfff", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 3) Gonadal Sheath Cells](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "hash": "fcda8cee4b3cc3c37657fdc892fb5f84792b29c1e2d98ce123f434f9cb089a1b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Five pairs of thin gonadal sheath cells form a single layer covering the germ-line component of each arm. Each pair occupies a stereotyped position along the gonad proximal\u00e2\u0080\u0093distal axis. The neighboring sheath-cell borders partially overlap, and occasional gap junctions and macular adherens junctions are observed between cells in these regions (see also Gap Junctions). Sheath cells are intimately associated with the germ line and are necessary for several aspects of germ-line development. Sheath cells or their precursors promote germ-line proliferation and exit from pachytene, gametogenesis, and male gamete fate during germ-line sex determination (Seydoux et al., 1990; McCarter et al., 1997; Rose et al., 1997; Killian and Hubbard, 2004). In the adult, distal sheath cells engulf germ cells eliminated by programmed cell death (see Reproductive system - Germ Line). Proximal sheath cells are necessary for oocyte maturation and ovulation and function permissively in the process of yolk protein uptake by oocytes (Grant and Hirsh, 1999; Hall et al., 1999; McCarter et al., 1999).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1089, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "56dce593-24bf-4009-b778-126740d825b4": {"__data__": {"id_": "56dce593-24bf-4009-b778-126740d825b4", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 3) Gonadal Sheath Cells](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e5b933db-8b7a-4e6e-b5b4-6385102fee49", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 3) Gonadal Sheath Cells](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "hash": "b2b2070964d8413d0cfa007916715b60bad25caac72781b20fdabc77ae22c12c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sheath cells arise from the SS blast cells present in the L2/L3 SPh (SomaticFIG 1, SomaticFIG 5A). During gonadogenesis, sheath cells reach their final distal\u00e2\u0080\u0093proximal location either by being pulled along with or crawling along the growing germ line (Kimble and Hirsh, 1979; McCarter et al., 1997). Distal and proximal sheath cells of the adult express quite different characteristics. Sheath-cell pair 1 (SomaticFIG 5B-E), which overlies the distal germ line, in particular, is strikingly different from the more proximal pairs 3\u00e2\u0080\u00935, which overlie developing oocytes. Pair 2, located over the loop, appears to express properties intermediate to the distal and proximal pairs.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 680, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7d9dd511-8512-47cb-b7be-e885f0cfb53c": {"__data__": {"id_": "7d9dd511-8512-47cb-b7be-e885f0cfb53c", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 3.1) Distal Sheath-cell Pair 1](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "10c977e1-b9da-4d77-ac00-efa4bc2bbc2f", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 3.1) Distal Sheath-cell Pair 1](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "hash": "a8c7ea5e9d987a727c7f49d02e23a84cec0c17a92cc7f9d74c320b95ea1153d7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The cytoplasm of these cells forms concentrated wedges between germ cells and a thin layer over them, giving pair 1 a net-like appearance (SomaticFIG 5D and SomaticFIG 6A). Distally, cells extend filopodia that form an irregular meshwork running between germ cells (Hall et al., 1999). Beneath this distal sheath pair, germ cells are gradually flowing proximally toward the loop, propelled by both the generation of new germ cells distally and the loss of some germ cells to apoptosis and/or ovulation more proximally. Thus, the distal sheath cells may be in a perpetually crawling phase, just to keep their place over the moving germ line.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 640, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c6f10180-80f5-467d-a798-bb77ed324431": {"__data__": {"id_": "c6f10180-80f5-467d-a798-bb77ed324431", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 3.2) Proximal Gonad Sheath-cell Pairs](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0c768064-0aa3-4d79-b069-71101241229d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 3.2) Proximal Gonad Sheath-cell Pairs](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "hash": "bdc098df847af446ea3c3be967b521d4e7542c963ff3657d7b11f7b9cd58f98d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Pairs 3\u00e2\u0080\u00935 differ dramatically from sheath-cell pair 1 in their morphology and ultrastructural characteristics (SomaticFIG 5A and SomaticFIG 5D&E). Pairs 3\u00e2\u0080\u00935 express muscle components such as the filament proteins actin (detected with rhodamine phalloidin) and myosin, and the thin filament-associated muscle protein UNC-87 (Hirsh et al., 1976; Strome, 1986; Goetinck and Waterston, 1994; McCarter et al., 1997). These filaments are organized into dense networks. In pairs 3 and 4, filaments are predominantly longitudinally oriented, whereas in pair 5, filaments are both longitudinally and circumferentially oriented (SomaticFIG 5E). Filaments are also present in the distal sheath cells but are much less abundant. The presence of dense networks in proximal cells is consistent with their contractile properties. Proximal sheath contraction is required for ovulation and transfer of the oocyte into the spermatheca for fertilization. During ovulation, proximal sheath-cell contraction pulls the dilated spermatheca over the proximalmost oocyte. Neither the sheath nor the spermatheca (see below) appears to be innervated. Therefore, these tissues may be similar to arterial smooth muscle and potentially regulate contraction and relaxation through calcium sparks (see Bui and Sternberg, 2002, and references therein).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1323, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e2f10434-bc73-4768-ba5a-3edac7a4cb26": {"__data__": {"id_": "e2f10434-bc73-4768-ba5a-3edac7a4cb26", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 3.2) Proximal Gonad Sheath-cell Pairs](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7ac131a3-bc8a-4f05-ba7a-7b2a21dc403d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 3.2) Proximal Gonad Sheath-cell Pairs](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "hash": "4e6677a00b5cd9f8ec194676e715a7bee00853a7d848d4e433a0cd241cb7a730", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Gap junctions are seen occasionally between sheath cells and between the apical sheath-cell surface and oocytes (SomaticFIG 6C&D) (Hall et al., 1999) (see also Gap Junctions). Contraction of sheath cells is coupled to oocyte maturation and the presence of sperm (see Reproductive System - Germ Line; McCarter et al., 1999; Miller et al., 2001, 2003). Sheath:sheath and sheath:oocyte gap junctions may therefore facilitate the coordination of the oocyte stage and sheath contraction rate with the presence of sperm. Sheath-cell pairs 4 and 5 also contain numerous pores (SomaticFIG 6B). Yolk particles produced in the intestine pass through the gonadal basal lamina and the sheath pores, gaining entry to the oocytes by the process of endocytosis (Grant and Hirsh, 1999; Hall et al., 1999).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 789, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "654a92c9-6a13-4767-b388-bda31fd7a03c": {"__data__": {"id_": "654a92c9-6a13-4767-b388-bda31fd7a03c", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 4) The Spermatheca](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9e6bbe03-19a2-4e28-8d46-49c825242dea", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 4) The Spermatheca](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "hash": "523e362a311348239a266b3c4576fbf913aa6b797778ffac484697e40adff983", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The spermatheca, the site of oocyte fertilization, is an accordion-like tube that contains sperm. It is composed of 24 cells organized into two regional groups: distally, 8 cells aligned in two rows that form a narrow corridor or neck, and proximally, 16 cells that form a wider bag-like chamber (Kimble and Hirsh, 1979; McCarter et al., 1997).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 344, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "191e868c-731c-4548-ac5b-0ea8203b79f1": {"__data__": {"id_": "191e868c-731c-4548-ac5b-0ea8203b79f1", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 4) The Spermatheca](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "344818a1-a4f8-4b40-8e79-13110de22be7", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 4) The Spermatheca](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "hash": "9a9c9e61906d3fba8ffc38c9f5e469fc4cbdf7fa18b93295ce72c08c266ab96f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In the absence of an oocyte, the adult spermatheca lumen is narrow and the apical surfaces of cells lining it are highly convoluted, providing the potential for expansion and an adherent surface for sperm (SomaticFIG 7A; compare SomaticFIG 8A&B). The outer (basal) surface displays numerous longitudinal folds of collapsed membranes (SomaticFIG 7A) that may also allow for the radial expansion of the spermatheca during oocyte passage.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 435, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9071d21c-13c6-48d8-88d9-3d7c2eca5a00": {"__data__": {"id_": "9071d21c-13c6-48d8-88d9-3d7c2eca5a00", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 4) The Spermatheca](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b9914218-ba04-4a59-84ea-bc58ed680849", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 4) The Spermatheca](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "hash": "d484bd510ed06bad9a791bf643733992ae5b97acdd16d46ca57bd7e7967e9fed", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Spermathecal cells are rich in actin microfilaments that are organized into circumferentially oriented networks (SomaticFIG 8C). Myosin, however, has not yet been detected (Strome, 1986; McCarter et al., 1997). Circumferential dilation of the distal spermatheca during ovulation is triggered in response to activation of the LIN-3/LET-23 receptor tyrosine kinase (RTK) pathway by the maturing primary oocyte (see Reproductive System - Germ Line). Pathway activation causes an increase in IP3 levels, which leads to dilation, possibly by a mechanism involving calcium release (Clandinin et al., 1998; McCarter et al., 1999; Bui and Sternberg, 2002). Tight regulation of inositol-1,4,5-triphosphate (IP3) levels appears to be necessary to ensure that dilation is strictly controlled so that only one oocyte at a time is enveloped by the spermatheca (Bui and Sternberg, 2002). Gap junctions are located on the lateral borders between sheath and spermathecal cells (see Gap Junctions). These could serve to synchronize spermatheca dilation and relaxation with contraction of the sheath.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1082, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "dcea2dd9-8a0c-43f1-8e4a-615de6f9d191": {"__data__": {"id_": "dcea2dd9-8a0c-43f1-8e4a-615de6f9d191", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 4) The Spermatheca](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8faa4d8d-c0c3-4569-b8a1-571bcededbdb", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 4) The Spermatheca](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "hash": "05c272ae39e905b7fe98fe718eec8c348ab8034684815426288ec41ff31cefcd", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Spermathecal cells arise from SS and DU blast cells of the somatic primordium; 18 cells are the products of the SS cells and 6 derive from the DUs (SomaticFIG 1; SomaticFIG 5A) (Kimble and Hirsh, 1979; Newman et al., 1996; McCarter et al., 1997). The terminal cells form a spermatheca with a lumen by late L4; however, this organ does not achieve its adult form until the first oocyte has passed through it (J. White, unpubl.). Before the first ovulation, the newly formed spermatheca is devoid of sperm (SomaticFIG 9A and see GermFIG 6). Male gametes are generated in the gonadal sheath lumen and remain there until passage of the first mature oocyte pushes them into the spermatheca. This first ovulation event also results in loss or reduction of numerous filopodia that extend from apical membranes into the spermathecal lumen (SomaticFIG 9C) (D.H. Hall, unpubl.; J. White, unpubl.).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 887, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a7418081-0681-4950-8a3c-846ea09bf171": {"__data__": {"id_": "a7418081-0681-4950-8a3c-846ea09bf171", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 4) The Spermatheca](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8c3ef34a-08d9-4ac6-b823-6f4b52ad5d0c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 4) The Spermatheca](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "hash": "2b1ec09cc5fd2e182c0f979587067b27f76045fa8ac1db2ec8668b28a510798f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Maturing spermathecal cells (SomaticFIG 9B) have a dark cytoplasm (granular by differential interference contrast [DIC] microscopy) and are covered by a thick basal lamina on their basal surface. Cells are organized into a spiral structure with a single left-handed twist along the organ\u00e2\u0080\u0099s anterior\u00e2\u0080\u0093posterior axis. This arrangement likely contributes to the complex twisting of cell borders, which are hard to resolve, even at high magnification. Each cell contributes a portion of its apical side to the lumenal surface and its basal side to the outer surface of the tissue. Cell surfaces bear a variety of junction types, several of which are recognized by the anti-AJM-1 antibody MH27: the adherens, pleated septate, and smooth/continuous septate junctions (SomaticFIG 8A,B; SomaticFIG 9C; Somatic FIG 9EF) (D.H. Hall, unpubl.). Apical surfaces bear adherens and pleated septate junctions, whereas lateral surfaces bear smooth/continuous septate and gap junctions (SomaticFIG 9B\u00e2\u0080\u0093D; Somatic FIG 9EF). The pleated septate and continuous junctions, on either side of the adherens junctions, may zip and unzip as oocytes pass through the organ (SomaticFIG 9D) (J. White, pers. comm.).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1189, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e7dd17c0-9f3b-44a0-b19d-f19860f9ffe1": {"__data__": {"id_": "e7dd17c0-9f3b-44a0-b19d-f19860f9ffe1", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 5) The Spermathecal-uterine Valve](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "20086912-5fa4-4d63-85dd-e222ce188574", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 5) The Spermathecal-uterine Valve](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "hash": "068c29721f7605ecbf6a1da3f2dcfbc7412dc0390936c346d364ac27b78b6478", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "After oocyte fertilization, the newly formed embryo passes from the spermatheca to the uterus via a connecting valve, the sp-ut valve (SomaticFIG 10A). The adult valve consists of a toroidal syncytium generated by the fusion of four cells (sujns) (SomaticFIG 10C) (Kimble and Hirsh, 1979).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 289, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "51913fcc-d256-4108-91e1-38d316a297ba": {"__data__": {"id_": "51913fcc-d256-4108-91e1-38d316a297ba", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 5) The Spermathecal-uterine Valve](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "11d70dd8-5659-4cff-be6a-499996b0de2c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 5) The Spermathecal-uterine Valve](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "hash": "b119488082c1e5f3104aad6df93692faeabf3f79ecc17e5410b6157c6b5b3eba", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Like the spermatheca, the morphology of the sp-ut valve is altered by passage of the first fertilized oocyte. Before the first ovulation, the center of the toroid is occupied by two junctional core cells, also syncytial (sujcs) (Kimble and Hirsh, 1979). The core cells extend pseudopodia into the apical folds of the sujn cells, and core cell nuclei protrude into the uterus lumen (SomaticFIG 10B&C) (Kimble and Hirsh, 1979). Passage of the first fertilized oocyte apparently pushes the core cell bodies away to open the passage. The fate of the displaced core cells is not known.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 580, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0ddc2702-c53f-4365-bcc2-5dd50ffe57d0": {"__data__": {"id_": "0ddc2702-c53f-4365-bcc2-5dd50ffe57d0", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 5) The Spermathecal-uterine Valve](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "dfee16f3-f089-4ad7-ab93-f65c77fc40cb", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 5) The Spermathecal-uterine Valve](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "hash": "805e0c885e6c9a95bf277d97ae1c38574c3cc87d4518c961cf37f484bdd8cf60", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The anatomy of the sujn valve cells has been followed in serial sections (E. Southgate and J. White, pers. comm.). The outward (basal surface) of the valve is encircled by a thick basal lamina. At its apical (lumenal) face, valve membranes appear to zip together by pleated septate junctions, in the same manner as the spermatheca, thus sealing the lumen when empty (SomaticFIG 10C). Valve cells extend many interlocking fingers into the valve-spermatheca interface. These, together with possible adherens and septate junctions, may serve to hold the adjacent tissues together. On the opposite side, where the valve faces the nearest uterine epithelial cells (ut4), the lateral cell borders contain extensive septate junctions and possibly some adherens junctions.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 764, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1cf9c1ea-93a4-41a9-b674-c9f9f78f4be6": {"__data__": {"id_": "1cf9c1ea-93a4-41a9-b674-c9f9f78f4be6", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 6) List of Somatic Gonad Cells](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1748d288-aefb-4e27-b0b8-e154709889c7", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 6) List of Somatic Gonad Cells](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "hash": "e6bef812109c75c51ce8a12a31986120ad8b4335d21a088aa5f478771ae3d736", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "1. Late L2/early L3 stage SPh", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 29, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "23252eae-25f6-40fc-b222-4aedddb54ac3": {"__data__": {"id_": "23252eae-25f6-40fc-b222-4aedddb54ac3", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 6) List of Somatic Gonad Cells](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "586e0fec-6373-44c2-8976-5325f2b70524", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 6) List of Somatic Gonad Cells](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "hash": "c09a3cd3bb60f36e1fcb5325438d40c0dab37236490ae9cdb1e97f7a5d805c72", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Z1.aa (Distal Tip Cell, anterior)\n\n SS, Z1.ap (Somatic sheath and Spermatheca precursor)\n\n SS, Z1.paa (Somatic sheath and Spermatheca precursor)\n\nDU, Z1.pap (Dorsal Uterine precursor; generates uterus, spermatheca and spermatheca-uterine valve cells)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 250, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1dcd02b9-da55-4eca-b93e-829fe5a736ea": {"__data__": {"id_": "1dcd02b9-da55-4eca-b93e-829fe5a736ea", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 6) List of Somatic Gonad Cells](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "56f9a99d-3a32-4877-9f64-f27d6754e76d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 6) List of Somatic Gonad Cells](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "hash": "9671db0ff2d3feafa4d0fefd1cd825e178b2cb2e5da9f35f386eea4c9cf2363f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "VUs and AC are of either the 5R or 5L configuration:\n\n5R configuration\n\nVU, Z1.ppa (Ventral Uterine precursor; generates uterus, spermatheca and spermatheca-uterine valve cells) \n\nAC, Z1.ppp (Anchor Cell) \n\nVU, Z4.aaa (Ventral Uterine precursor; generates uterus, spermatheca and spermatheca-uterine valve cells) \n\nVU, Z4.aap (Ventral Uterine precursor; generates uterus, spermatheca and spermatheca-uterine valve cells)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 420, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "74db2b54-e75e-4188-b87e-dda42833a8ef": {"__data__": {"id_": "74db2b54-e75e-4188-b87e-dda42833a8ef", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 6) List of Somatic Gonad Cells](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ed91e4ee-bcf0-468b-a55f-448871eb3f2b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 6) List of Somatic Gonad Cells](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "hash": "4a39c245947f1c5fa19864c1d51b78f193ef5ed48045c791515586210e2392e4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "5L configuration\n\nVU, Z1.ppa (Ventral Uterine precursor; generates uterus, spermatheca and spermatheca-uterine valve cells) \n\nVU, Z1.ppp (Ventral Uterine precursor; generates uterus, spermatheca and spermatheca-uterine valve cells) \n\nAC, Z4.aaa (Anchor Cell) \n\nVU, Z4.aap (Ventral Uterine precursor; generates uterus, spermatheca and spermatheca-uterine valve cells) \n\n\n\nDU, Z4.apa (Dorsal Uterine precursor; generates uterus, spermatheca and spermatheca-uterine valve cells) \n\n SS, Z4.app (Somatic sheath and Spermatheca precursor)\n\n SS, Z4.pa (Somatic sheath and Spermatheca precursor)\n\nZ4.pp (Distal Tip Cell, posterior)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 623, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "70f8d470-85df-4d5c-a612-a24bcde16422": {"__data__": {"id_": "70f8d470-85df-4d5c-a612-a24bcde16422", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 6) List of Somatic Gonad Cells](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4fe6ec14-cd87-4158-b9ce-f2a7e919a136", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 6) List of Somatic Gonad Cells](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "hash": "4e4ada2387e839be2da1ebcfc77341024a4d00f3abcb67d6facd64e66d96172d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "2. Adult anterior gonad arm", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 27, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0740cfa0-beb8-47a7-914a-4d111a4b2f1b": {"__data__": {"id_": "0740cfa0-beb8-47a7-914a-4d111a4b2f1b", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 6) List of Somatic Gonad Cells](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2d59a756-177d-48bb-95f9-0bc8048d48b6", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 6) List of Somatic Gonad Cells](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "hash": "32a79724c1eae16690c89cb2a0c06d3106ab915118a32577acd85f2cef9ed271", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "i. Distal Tip Cell of anterior gonad arm: Z1.aa", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 47, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "45292f53-6033-4798-b840-3250c059c135": {"__data__": {"id_": "45292f53-6033-4798-b840-3250c059c135", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 6) List of Somatic Gonad Cells](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b5cb9edf-f5a4-4e95-98d6-d1a6640fe444", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 6) List of Somatic Gonad Cells](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "hash": "704f5ccdb1d29cf5f1c9beb2d098c145ceb866e94e9814ba003197eed4f1b9fb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "ii. Somatic Sheath (10 cells/5 pairs) of anterior gonad arm: Z1.apa (sheath cell 1)\n\nZ1.appaaa (sheath cell 2)\n\nZ1.appaap (sheath cell 3)\n\nZ1.appapa (sheath cell 4)\n\nZ1.appapp (sheath cell 5)\n\nZ1.paaa (sheath cell 1)\n\nZ1.paapaaa (sheath cell 2)\n\nZ1.paapaap (sheath cell 3)\n\nZ1.paapapa (sheath cell 4)\n\nZ1.paapapp (sheath cell 5)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 328, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "61e4a876-3c41-46ea-b5dc-4c38a047ad28": {"__data__": {"id_": "61e4a876-3c41-46ea-b5dc-4c38a047ad28", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 6) List of Somatic Gonad Cells](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "706915c7-44fa-4460-a98b-4d85d4980dab", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 6) List of Somatic Gonad Cells](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "hash": "54cd49e0c550ab82d2a96f55c94dd3431110086084ff934e012fc33ae9095a96", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "iii. Spermatheca (24 cells) of anterior gonad arm: Z1.apppaaaaZ1.apppaaapZ1.apppaapaZ1.apppaappZ1.apppapaaZ1.apppapapZ1.apppappZ1.appppaZ1.apppppZ1.paappaaaaZ1.paappaaapZ1.paappaapaZ1.paappaappZ1.paappapaaZ1.paappapapZ1.paappappZ1.paapppaZ1.paappppZ1.papaaadZ1.papaaavZ1.papaapvZ4.apaaaadZ4.apaaaavZ4.apaaapv", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 308, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2d78c686-e32c-45ee-9f17-88eb21a186b5": {"__data__": {"id_": "2d78c686-e32c-45ee-9f17-88eb21a186b5", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 6) List of Somatic Gonad Cells](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b18a48ec-3efd-442b-9d96-afc5a7021abb", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 6) List of Somatic Gonad Cells](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "hash": "cf5703e8dc1eceada9f135d4332e7e87c026ce61d0a2b913f1b9d8a6bcc5b256", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "iv. Spermatheca-uterine valve and core (both syncytial) of anterior gonad arm: Z1.papaapd; Z4.apaaapd (2 sujc cells that fuse to make the \"core\" syncytium, lost after the 1st ovulation)\n\nZ1.papapaaa; Z1.ppaaaaa; Z1.ppaaapa; Z4.apaapaaa (4 sujn cells that fuse to make the valve syncytium)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 288, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c70f891e-4e80-408f-ab91-e79684646310": {"__data__": {"id_": "c70f891e-4e80-408f-ab91-e79684646310", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 6) List of Somatic Gonad Cells](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a8e2fce7-6d45-480e-95a3-e12b1f9765c6", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 6) List of Somatic Gonad Cells](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "hash": "8a57ed64828c77ecfcd2e1fd3b09ea084713844c4700045ced033cf3b06480ed", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "3. Adult posterior gonad arm", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 28, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6e3389f6-da60-4914-bdf0-f3397e9ef303": {"__data__": {"id_": "6e3389f6-da60-4914-bdf0-f3397e9ef303", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 6) List of Somatic Gonad Cells](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c27d1e2d-bcbb-4fff-9b74-5d98d2921cd8", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 6) List of Somatic Gonad Cells](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "hash": "76b31c2bcabde3f4e1ffd53e3339fbf4a308210882de102dcfd521da230c4252", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "i. Distal Tip Cell of posterior gonad arm:\n\nZ4.pp", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 49, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c76c7b2a-73c9-47ea-979b-a23b6c3eef46": {"__data__": {"id_": "c76c7b2a-73c9-47ea-979b-a23b6c3eef46", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 6) List of Somatic Gonad Cells](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "86df114b-9275-485c-b16d-810559426d0f", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 6) List of Somatic Gonad Cells](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "hash": "37f46a9da57bd363dc4b58de8aca7d9a9386ae34bbb7339a1cf6dcd1675834af", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "ii. Somatic Sheath (10 cells/5 pairs) of posterior gonad arm: Z4.pap (sheath cell 1)\n\nZ4.paappp (sheath cell 2)\n\nZ4.paappa (sheath cell 3)\n\nZ4.paapap (sheath cell 4)\n\nZ4.paapaa (sheath cell 5)\n\nZ4.appp (sheath cell 1)\n\nZ4.appappp (sheath cell 2)\n\nZ4.appappa (sheath cell 3)\n\nZ4.appapap (sheath cell 4)\n\nZ4.appapaa (sheath cell 5)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 329, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "876b8c3f-09c7-44cb-8f2c-20a51b77e7f2": {"__data__": {"id_": "876b8c3f-09c7-44cb-8f2c-20a51b77e7f2", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 6) List of Somatic Gonad Cells](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1a07c816-9207-4fd3-915e-e92c3f47ff1c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 6) List of Somatic Gonad Cells](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "hash": "25400de0f9fbd88a95da9601ca1d8d920e11a0227df28ee030c31f849f46d9a7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "iii. Spermatheca (24 cells) of posterior gonad arm: Z1.papppavZ1.pappppdZ1.pappppvZ4.apappavZ4.apapppdZ4.apapppvZ4.appaaaaZ4.appaaapZ4.appaapaaZ4.appaapapaZ4.appaapappZ4.appaappaaZ4.appaappapZ4.appaapppaZ4.appaappppZ4.paaaaaZ4.paaaapZ4.paaapaaZ4.paaapapaZ4.paaapappZ4.paaappaaZ4.paaappapZ4.paaapppaZ4.paaapppp", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 309, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "bf7591c5-637a-4446-a926-4cd26fd66e93": {"__data__": {"id_": "bf7591c5-637a-4446-a926-4cd26fd66e93", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 7) References](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d1077f6e-3c04-40a1-8d38-b45178a853d7", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 7) References](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "hash": "56210da8b0a7227fe456bfaa80c956cda33c1b6e89abeab21dbbc175dab3c85c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Austin, J., and Kimble, J. 1987. glp-1 is required in the germ line for regulation of the decision between mitosis and meiosis in C. elegans. Cell 51: 589-599. Abstract", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 168, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "821e92b3-565b-41fd-b550-44f36a0e41f6": {"__data__": {"id_": "821e92b3-565b-41fd-b550-44f36a0e41f6", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 7) References](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c4375645-3876-4f48-8634-0010a383b2e5", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Somatic Gonad, Section 7) References](https://www.wormatlas.org/hermaphrodite/somatic gonad/Somframeset.html)"}, "hash": "14dc704c9a3c4c8056b50fd54a259aeedc9ab1af9f9fb4c3adffca9dce33fb00", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Blelloch, R., Anna-Arriola, S.S., Gao, D., Li, Y., Hodgkin, J. and Kimble, J. 1999. The gon-1 gene is required for gonadal morphogenesis in Caenorhabditis elegans. Dev. Biol. 216: 382-393. Article", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 196, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a8538585-d9bf-4883-b228-fa9ba97e9f6c": {"__data__": {"id_": "a8538585-d9bf-4883-b228-fa9ba97e9f6c", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Intestine, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/intestine/Intframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f1bbcf05-f759-4cc8-9ec6-af8ea927078d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Intestine, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/intestine/Intframeset.html)"}, "hash": "ab3f01297be36d2cd4e5af1af0fed1a3bd2ad08ba5179ba7f237eac129a12a99", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In C. elegans the intestine is a large organ that carries out multiple functions executed by distinct organs in higher eukaryotes, including digestion of food, absorption of processed nutrients, synthesis and storage of macromolecules, initiation of an innate immune response to pathogens, and nurturing of germ cells by producing yolk (IntFIG 1) (Kimble and Sharrock, 1983; Schulenburg et al., 2004; Pauli et al., 2006; McGhee, 2007). The intestine is comprised of 20 large epithelial cells that are mostly positioned as bilaterally symmetric pairs to form a long tube around a lumen. Each of these cell pairs forms an intestinal ring (II-IX int rings). The anteriormost intestinal ring (int ring I) is an exception and is comprised of four cells (IntFIG 2). Although the intestine initially fills the entire body cavity behind the pharynx, it becomes deflected to permit the outgrowth of the gonad within the same cavity as the animal ages. The intestine is not rigidly attached to the body wall; rather, it is firmly anchored to the pharyngeal and rectal valves at either end. More tenuous linkages between the basal laminae of the intestine and the body wall form via lengthwise stripes of hemicentin (Vogel and Hedgecock, 2001). The intestine is not directly innervated and has only one associated muscle (the stomatointestinal muscle) at its posterior extreme (see Muscle System - Nonstriated).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1400, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ee18d6e8-801c-4529-8e87-ab098c5e9d64": {"__data__": {"id_": "ee18d6e8-801c-4529-8e87-ab098c5e9d64", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Intestine, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/intestine/Intframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7ab4b1e1-8443-4c14-a917-3cb93e1fc341", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Intestine, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/intestine/Intframeset.html)"}, "hash": "bc8dc2b3d02d8153f9b09ff00e60ceddef85a1892a4bde012789dd487f59ac44", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The adult intestine shows a dextral handedness to its position along the length of the animal such that in the anterior, it is localized to the left side and in the posterior, to the right side (IntFIG 1) (Wood et al., 1996).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 225, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "03acc135-2c91-4880-833d-1377caafb6d9": {"__data__": {"id_": "03acc135-2c91-4880-833d-1377caafb6d9", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Intestine, Section 2) Intestinal Development: Transcriptional Mechanisms](https://www.wormatlas.org/hermaphrodite/intestine/Intframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8aef555e-529e-455a-bb18-0eeb0ccb40f5", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Intestine, Section 2) Intestinal Development: Transcriptional Mechanisms](https://www.wormatlas.org/hermaphrodite/intestine/Intframeset.html)"}, "hash": "82c43f4fc0956d051cd265f5ed746ac77ed82c9ed78d2360a0f20b9bb955f141", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The control of cell fates within C. elegans lineages is primarily determined by cell-autonomous transcriptional decisions within each cell, but there are a few levels at which inductive signals from other cells can impact these decisions. In the case of the intestine, these mechanisms have been explored in detail and thus provide an excellent example of how this animal regulates cell fates.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 393, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c03fed5f-49b9-4629-912a-66f16d8d0e1f": {"__data__": {"id_": "c03fed5f-49b9-4629-912a-66f16d8d0e1f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Intestine, Section 2) Intestinal Development: Transcriptional Mechanisms](https://www.wormatlas.org/hermaphrodite/intestine/Intframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7828c083-a51a-4eef-ba07-9beb6ca6baea", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Intestine, Section 2) Intestinal Development: Transcriptional Mechanisms](https://www.wormatlas.org/hermaphrodite/intestine/Intframeset.html)"}, "hash": "7e0b5665f920c6b3637511a6fb1e58959650970a643c8bff9102d47567a0ff97", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Unlike many lineages, the intestinal cells derive from a single progenitor cell E, such that the clonal proliferation of the E lineage constitutes the whole intestine (Goldstein, 1992). Some maternally contributed mRNAs play key roles in the transcriptional patterns in early steps of this lineage. E is the posterior daughter of the mesendodermal precursor EMS, whereas the anterior daughter is the mesodermal precursor MS. EMS itself derives from the blast cell P1, which divides to generate EMS and P2 (AlimFIG 1). During regulation of early blastomere fates, a transcription factor SKN-1, whose mRNA is contributed maternally, is produced asymmetrically at high levels in P1 and its descendants. (Schnabel and Priess, 1997; Maduro and Rothman, 2002). In EMS, SKN-1 activates expression of med genes, encoding GATA-type transcription factors, and marks the switch from maternal to zygotic control in mesendoderm specification. Downstream from MED proteins, other GATA-type transcription factors carry out intestinal differentiation and maintenance through activation of intestine specific genes encoding, among others, an acid-phosphatase, a cysteine protease and metallothioneins, which results in a fully-functional intestine.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1231, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "70813130-4668-461f-860f-06434f686c8f": {"__data__": {"id_": "70813130-4668-461f-860f-06434f686c8f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Intestine, Section 2) Intestinal Development: Transcriptional Mechanisms](https://www.wormatlas.org/hermaphrodite/intestine/Intframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6d7c0364-f6a3-43b9-8961-940ae135d41e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Intestine, Section 2) Intestinal Development: Transcriptional Mechanisms](https://www.wormatlas.org/hermaphrodite/intestine/Intframeset.html)"}, "hash": "3faf7276c0191f26f840f80019842a854030042b6c1187aa533ec9540789b210", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In addition to these transcriptional cascades, a cell-cell inductive interaction between EMS and P2 is required to produce an endoderm-producing E cell in a 4-cell embryo (IntFIG 3). Through this interaction, which involves Wnt/MAPK signaling, the posterior part of EMS that contacts P2 gives rise to the E blastomere, whereas the anterior part produces MS. In the absence of this cell-cell communication, EMS divides symmetrically into two MS-like cells (Goldstein, 1993; Lin et al., 1995; Lin et al., 1998; Rocheleau et al., 1999; Maduro and Rothman, 2002).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 559, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2e2486c3-a982-49c5-b3ae-c1a72e4af907": {"__data__": {"id_": "2e2486c3-a982-49c5-b3ae-c1a72e4af907", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Intestine, Section 3) Intestinal Development: Structural Mechanisms](https://www.wormatlas.org/hermaphrodite/intestine/Intframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a7a6f1eb-fc53-46e4-ae53-fb8098a1d17c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Intestine, Section 3) Intestinal Development: Structural Mechanisms](https://www.wormatlas.org/hermaphrodite/intestine/Intframeset.html)"}, "hash": "385a14a7dc9429cb4e4355992c42f5c0e00fb0f5c91a9a7f330023f29c04aaaf", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The E blastomere is born on the surface of the embryo at about 35 min after fertilization (IntFIG 3). From this point on, the specific stages of intestinal development are indicated by the number of E descendants present such as E2, E4, E8, E16 and E20, although occasionally due to an extra cell division during development the mature intestine is seen to be made of 21 cells instead of the usual 20 (Sulston and Horvitz, 1977). The daughters of E, E.a and E.p, migrate into the interior of the embryo initiating gastrulation when the embryo is at the 26-cell stage (Bucher and Seydoux, 1994, Nance et al., 2005). At the E16 stage, the intestinal primordium has a ventral tier of six cells and a dorsal tier of ten cells (IntFIG 4). About 30 min into the E16 stage, cytoplasmic polarization of intestinal cells occurs such that the nuclei of cells move towards and cytoplasmic components move away from the midline (Leung et al., 1999). Shortly afterwards, cell separation starts at the midline as small gaps, and these small gaps eventually become the lumen of the intestine. At the same time, electron-dense vesicles begin to appear in the cytoplasm and localize near the basal pole. These vesicles may correspond to the intestine-specific gut granules (IntFIG 1). At E16-E20, two ventral cell pairs intercalate between the dorsal cells, resulting in a single layer of intestinal cells with bilateral symmetry. As the second cell intercalation occurs, neighboring int II, int III and int IV rings initiate a coordinated 90\u00b0 clockwise rotation around the axis of the midline. Between 430 min following first cell division and hatching, intestinal rings VII-IX make coordinated 90\u00b0 counter-clockwise rotation which leads to the twisted appearance of the intestine in the newly hatched larva (IntFIG 3) (Sulston and Horvitz, 1977; Mendenhall et al., 2015). As a result, int 5L connects to int 4V and int 6L connects to int 7L in the adjoining rings (Mendenhall et al., 2015; A. Mendenhall, pers. comm.; Z. F. Altun and D. H. Hall, unpub. observations). The cells in int V and/or int VI rings get variably pushed to the right or left side by the developing uterus in subsequent stages and, hence, their nuclei are stochastically located to the right or left of the midline. The forces or developmental processes that influence the positions of these cells in postembryonic life are still unknown. By the adult stage, the intestine is composed of 20 cells with a total of 30-34 nuclei and 32C per nucleus (IntFIG 4X).These cell movements result in a superhelical twist of the intestine, displacing the anterior half to the left side of the larval body and the posterior half to the right side. This twist of the intestine, in turn, is suggested to lead to the asymmetrical growth of the gonad later in life (Hermann et al., 2000). The left-right rotational asymmetry of this twist is determined by the LIN-12/Notch pathway and involves LAG-2, APX-1 and LAG-1 proteins. Also a pathway involving POP-1 and LIT-1 limits this twist to the anterior half of the intestine. Subsequently, the intestinal primordium elongates (Hermann et al., 2000). By the time of hatching, the anterior intestinal rings may make an additional 90\u00b0 rotation (IntFIG 2 and IntFIG 3) (Sulston and Horvitz, 1977). This second turn of the anterior intestinal cells seems to be variable, however, because cells in int II-IV rings can often be seen as dorsoventral to each other in adult animals. Similarly, orientation of cells in the adult int VI-IX rings is variable. Rings VI-VIII tend to adopt L/R positions, whereas ring IX cells are usually positioned dorsoventrally (Z.F. Altun and D.H. Hall, unpubl.).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 3676, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "adb1ddc4-088d-4453-8fad-05ed609df0a0": {"__data__": {"id_": "adb1ddc4-088d-4453-8fad-05ed609df0a0", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Intestine, Section 3) Intestinal Development: Structural Mechanisms](https://www.wormatlas.org/hermaphrodite/intestine/Intframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1f9693e9-af5a-460c-aee1-ae337a7a9706", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Intestine, Section 3) Intestinal Development: Structural Mechanisms](https://www.wormatlas.org/hermaphrodite/intestine/Intframeset.html)"}, "hash": "59dc37667672d272bedbfb38af61b72bce888c1f9ee2c1f9114752a7efa9123a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "During epithelial polarization, which follows cell intercalation, punctate foci of adherens junction proteins organize into rectilinear junctions surrounding the lumen of the intestine. Through this process, each cell acquires distinctive apical and basal surfaces. During subsequent embryogenesis, the apical membranes of cells between the adherens junctions increase greatly in area as microvilli develop, and correspondingly, the apical surface of the intestine expands. In addition, later, the cytoplasmic polarization disappears so that intestinal nuclei are found in the center of the cells and other organelles are more evenly dispersed within the cytoplasm (Leung et al, 1999).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 685, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "981a065e-b7c1-491f-a5e7-c6b982befc5a": {"__data__": {"id_": "981a065e-b7c1-491f-a5e7-c6b982befc5a", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Intestine, Section 3) Intestinal Development: Structural Mechanisms](https://www.wormatlas.org/hermaphrodite/intestine/Intframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0fae0ee5-6ce1-4f08-9c50-4f4688be6d90", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Intestine, Section 3) Intestinal Development: Structural Mechanisms](https://www.wormatlas.org/hermaphrodite/intestine/Intframeset.html)"}, "hash": "372e160c9eea88d1c611ef5a963b53f9544676331d0c4269fae781a0e74f2f9b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Intestinal cells become binucleate and polyploid during post-embryonic development (Hedgecock and White, 1985). At the beginning of the lethargus of the first molt, most of the intestinal nuclei, except the anteriormost 6, divide without accompanied cell divisions giving rise to 20 intestinal cells with a total of 30-34 nuclei. Despite a large increase in tissue volume, the intestine continues to grow without further cell or nuclei divisions. Intestinal nuclei continue to increase in size and go through repeated endoreduplications (chromosome duplication without karyokinesis), increasing the ploidy of each nucleus to 32C by the final molt. These endoreduplications are generally synchronized to each period of lethargus, resulting in a twofold increase in chromosomal number at the end of each molt. By the adult stage, the intestine is composed of 20 cells with a total of 30-34 nuclei and 32C per nucleus.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 915, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "feda8b2e-ddc0-4672-9ab8-1d1a260ec276": {"__data__": {"id_": "feda8b2e-ddc0-4672-9ab8-1d1a260ec276", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Intestine, Section 4) Intestine Structure and Function](https://www.wormatlas.org/hermaphrodite/intestine/Intframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6fc1b4e1-c8ab-4c18-9770-d96a4ae4fdbd", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Intestine, Section 4) Intestine Structure and Function](https://www.wormatlas.org/hermaphrodite/intestine/Intframeset.html)"}, "hash": "2c979c814f030bfd37f07c2b11947d4e51a937bc6eb11a6fc83bbf16a9205fdc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The intestine is composed of large, cuboidal cells, with distinct apical, lateral and basal regions (IntFIG 5) (see also Gap Junctions). Each intestinal cell forms part of the intestinal lumen at its apical pole and secretes the constituents of the basal lamina from its basal pole. The intestinal basal lamina contains laminin \u03b1 and \u03b2 nidogen/entactin, which are made by the intestine, and type IV collagen, which is made by the muscle and somatic gonad (Graham et al., 1997; Kang and Kramer, 2000; Huang et al., 2003; Kao et al., 2006). Each intestinal cell is sealed laterally to its neighbors by large adherens junctions close to the apical side (Labousse, 2006). It also connects to the neighboring intestinal cells via gap junctions on the lateral sides (IntFIG 5). The lateral membranes also display a region of tightly folded plasma membranes that may represent another specialized intercellular junction of novel form.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 927, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d12a4d9e-0ca3-4170-8e54-831f517665b8": {"__data__": {"id_": "d12a4d9e-0ca3-4170-8e54-831f517665b8", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Intestine, Section 4) Intestine Structure and Function](https://www.wormatlas.org/hermaphrodite/intestine/Intframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d591a9b9-1872-413c-91ad-10216c145bbd", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Intestine, Section 4) Intestine Structure and Function](https://www.wormatlas.org/hermaphrodite/intestine/Intframeset.html)"}, "hash": "4050169009a7099833daa8791eb15564d06f6e3f938a00aece286a2b848fd239", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Many microvilli extend into the lumen from the apical face, forming a brush border (IntFIG 5). The microvilli are anchored into a strong cytoskeletal network of intermediate filaments at their base, called the terminal web. The core of each microvillus has a bundle of actin filaments that connects to this web. Over the microvilli, there is an extracellular electron-lucent coating of highly modified glycoproteins (a glycocalyx), which may function to localize digestive enzymes, protect microvilli from physical or toxic injury or serve as a filter (Lehane, 1997). The villi may be somewhat shorter in the first int ring than in subsequent cells along the body axis (Sulston and Horvitz, 1977).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 697, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9c682b9f-0e13-4e9a-b2d0-0ec90a5a1419": {"__data__": {"id_": "9c682b9f-0e13-4e9a-b2d0-0ec90a5a1419", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Intestine, Section 4) Intestine Structure and Function](https://www.wormatlas.org/hermaphrodite/intestine/Intframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cdba5bdb-27b2-46bf-a248-53fed37d1aab", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Intestine, Section 4) Intestine Structure and Function](https://www.wormatlas.org/hermaphrodite/intestine/Intframeset.html)"}, "hash": "0851b0a2a1e3c694850915c7421d693c8159e4a080a21fecdd5358caff3ca6cc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The intestinal cells are each very large and contain large nuclei with a prominent nucleolus, many mitochondria, extensive rough endoplasmic reticulum (RER), many ribosomes, and an extensive collection of membrane-bound vesicles and vacuoles. The nature of these organelles changes gradually as the animal ages. The digestive and metabolic activities of the intestine are central to the growth and development of the animal, and correspondingly, these organelles include yolk granules, recycling endosomes, autophagic vacuoles, and autofluorescent (gut) granules. Using light microscopy, some of these gut granules become visible as birefringent objects in older adults and are inferred to be secondary lysosomes involved in catabolism (Clokey and Jacobson, 1986).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 764, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a9bd0c08-6ac9-4160-8944-a318e1322010": {"__data__": {"id_": "a9bd0c08-6ac9-4160-8944-a318e1322010", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Intestine, Section 4) Intestine Structure and Function](https://www.wormatlas.org/hermaphrodite/intestine/Intframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8f2f2ee3-142e-4d0b-84a5-933caad38900", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Intestine, Section 4) Intestine Structure and Function](https://www.wormatlas.org/hermaphrodite/intestine/Intframeset.html)"}, "hash": "f14c578eed651373de1c029b423aec86cdc0374310befb34c518b190ab634da1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The primary function of intestinal cells seems to be digestive because they secrete digestive enzymes (e.g. cysteine protease endodeoxyribonuclease) into the lumen and take up processed material and nutrients. The intestine also seems to be a large storage organ because it contains a large number of assorted storage granules that change in size, shape and number during development (White, 1988). In hermaphrodites, the intestine is also involved in synthesis and secretion of yolk material that is then transported to the oocytes through the body cavity (Kimble and Sharrock, 1983). The intestinal contents may also play role in miscellaneous functions carried out by nonintestinal cells in higher animals. For instance, the glycosyltransferases, which function in carbohydrate metabolism, comprise more than 70 genes in the C. elegans genome, and at least some appear to be expressed in the digestive tract (Griffitts et al., 2003; McKay et al., 2004). In addition, along with muscle, intestine is thought to be the major organ in which fatty acid metabolism takes place. Through the function of a glyoxylate cyclase (SRH-1) yolk fatty acid-derived acetylcoenzymeA is converted to succinate, from which carbohydrates are synthesized (Liu et al., 1995).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1256, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4ec609d1-b544-42f7-a88f-f070f18a374e": {"__data__": {"id_": "4ec609d1-b544-42f7-a88f-f070f18a374e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Intestine, Section 4) Intestine Structure and Function](https://www.wormatlas.org/hermaphrodite/intestine/Intframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d0feddb7-ded7-4b08-86d3-37be09b62015", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Intestine, Section 4) Intestine Structure and Function](https://www.wormatlas.org/hermaphrodite/intestine/Intframeset.html)"}, "hash": "d4fcdb83b71ea1304f819fefc80d177ddcc289434f865795856e9041ea534dd8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Anatomical and gene expression data both suggest that these functions differ along the length of the organ. For instance, the collection of membrane-bound organelles and vacuoles is more diverse and much more extensive in int rings I and II than further posterior (Borgonie et al., 1995). Without histochemical staining, it is still difficult to assign functions to each type of endosome, but open vacuoles of the anterior organ were proposed to release digestive enzymes into the gut lumen. In support of this observation, cysteine protease (CPR-1) expression is restricted to the anterior portions (among int rings I-VI) of the intestine (Britton et al., 1998). Yolk and lipid vacuoles predominate in posterior portions of the intestine, and these cells may be more active in nutrient and energy storage.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 806, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a66a72d7-5d5f-4238-9283-f7fec16b263f": {"__data__": {"id_": "a66a72d7-5d5f-4238-9283-f7fec16b263f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Intestine, Section 4) Intestine Structure and Function](https://www.wormatlas.org/hermaphrodite/intestine/Intframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2d234bd2-8337-4a82-9adf-8913222275f8", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Intestine, Section 4) Intestine Structure and Function](https://www.wormatlas.org/hermaphrodite/intestine/Intframeset.html)"}, "hash": "44d4963a977793eecd1596aa0f5e56310007bd18d3ef1d5c7ddade52e57af37f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The posterior intestine also functions as the pacemaker of the defecation cycle. In C. elegans, defecation occurs in a rhythmic manner in tightly regulated cycles that are approximately 50 seconds long and have three distinct muscle contraction steps (see Alimentary system - Rectum). Inositol triphosphate (IP3) receptor-driven calcium oscillations in the posterior intestinal cells initiate the muscle contractions of the defecation cycle and the IP3 receptor is a central component of the timekeeping mechanism that regulates this behavioral rhythm (Dal Santo, 1999; see also Alimentary system - Rectum).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 607, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f492473d-815d-4efc-b603-7ae351a31242": {"__data__": {"id_": "f492473d-815d-4efc-b603-7ae351a31242", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Intestine, Section 4) Intestine Structure and Function](https://www.wormatlas.org/hermaphrodite/intestine/Intframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d2a8bea2-2f3c-4cb5-be64-2199e459ba8c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Intestine, Section 4) Intestine Structure and Function](https://www.wormatlas.org/hermaphrodite/intestine/Intframeset.html)"}, "hash": "7b167f290da4950f599efff808e2285156da0bca64a69ff4a6027ec7310a6adb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Recent studies show intestine functions as a cold temperature sensor (intestinal cells exhibit a robust increase in calcium level in response to cooling).This calcium response is greatly reduced in trpa-1 mutant worms, consistent with an important role for TRPA-1 in cold-reception in intestine and cold-dependent lifespan extension (Xiao et al., 2013).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 353, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "97d89b4d-bd76-4bf9-9b17-286ffad0dce3": {"__data__": {"id_": "97d89b4d-bd76-4bf9-9b17-286ffad0dce3", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Intestine, Section 4) Intestine Structure and Function](https://www.wormatlas.org/hermaphrodite/intestine/Intframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c91fa45d-ca18-47d0-9bc4-20d2881e8573", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Intestine, Section 4) Intestine Structure and Function](https://www.wormatlas.org/hermaphrodite/intestine/Intframeset.html)"}, "hash": "9ec4d87f91bc56c8f451165d3ba1f806f49eda98c9efa6a6933d1b81817a1bb0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The intestine may change in shape and function rather dramatically in the dauer larva, which do not feed (Popham and Webster, 1979). The lumen becomes shrunken and the size and number of microvilli are greatly reduced (Albert and Riddle, 1988). When the animal emerges from the dauer state, these changes are reversed in the new L4 larva.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 338, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "39fe30b9-315e-44b3-899d-ecaa5fbcb9cf": {"__data__": {"id_": "39fe30b9-315e-44b3-899d-ecaa5fbcb9cf", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Intestine, Section 5) List of Intestinal Cells](https://www.wormatlas.org/hermaphrodite/intestine/Intframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8d039750-e53d-4125-918b-5a796126425b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Intestine, Section 5) List of Intestinal Cells](https://www.wormatlas.org/hermaphrodite/intestine/Intframeset.html)"}, "hash": "afdfb44a3c4607e33293bdfcf6ffe54aad93e25e73c219f1fd22c3473050ca81", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "1. First intestinal ring\n\nint1DL\n\nint1DR\n\nint1VL\n\nint1VR\n\n2. Second intestinal ring\n\nint2D\n\nint2V\n\n3. Third intestinal ring\n\nint3D\n\nint3D.a - postembryonic nuclear division\n\nint3D.p - postembryonic nuclear division\n\nint3V\n\nint3V.a - postembryonic nuclear division\n\nint3V.p - postembryonic nuclear division\n\n4. Fourth intestinal ring\n\nint4D\n\nint4D.a - postembryonic nuclear division\n\nint4D.p - postembryonic nuclear division\n\nint4V\n\nint4V.a - postembryonic nuclear division\n\nint4V.p - postembryonic nuclear division\n\n5. Fifth intestinal ring\n\nint5L\n\nint5L.a - postembryonic nuclear division\n\nint5L.p - postembryonic nuclear division\n\nint5R\n\nint5R.a - postembryonic nuclear division\n\nint5R.p - postembryonic nuclear division\n\n6. Sixth intestinal ring\n\nint6L\n\nint6L.a - postembryonic nuclear division\n\nint6L.p - postembryonic nuclear division\n\nint6R\n\nint6R.a - postembryonic nuclear division\n\nint6R.p - postembryonic nuclear division\n\n7. Seventh intestinal ring\n\nint7L\n\nint7L.a - postembryonic nuclear division\n\nint7L.p - postembryonic nuclear division\n\nint7R\n\nint7R.a - postembryonic nuclear division\n\nint7R.p - postembryonic nuclear division\n\n8. Eighth intestinal ring\n\nint8L\n\nint8L.a - postembryonic nuclear division\n\nint8L.p - postembryonic nuclear division\n\nint8R\n\nint8R.a - postembryonic nuclear division\n\nint8R.p - postembryonic nuclear division\n\n9. Ninth intestinal ring\n\nint9L\n\nint9L.a - postembryonic nuclear division\n\nint9L.p - postembryonic nuclear division\n\nint9R\n\nint9R.a - postembryonic nuclear division\n\nint9R.p - postembryonic nuclear division", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1557, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5961089d-fef9-46c4-a574-a3ac9fcb36f0": {"__data__": {"id_": "5961089d-fef9-46c4-a574-a3ac9fcb36f0", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 1) Nematode Nonstriated (Single Sarcomere) Muscle](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "24de061b-7af3-431b-b4bf-f313e85ce268", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 1) Nematode Nonstriated (Single Sarcomere) Muscle](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "hash": "3894839885978d47c26a56459fae85480c02fe319f47b14b2040cdeae5022f15", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Unlike the obliquely striated somatic muscles, which contain several to many sarcomeres repeating in regular order in one cell, nematode nonstriated muscles have either one or a few well-structured sarcomeres or myofilament networks that are less well organized. This group of muscles, also referred to as single-sarcomere muscles, includes pharyngeal, stomatointestinal, anal sphincter, anal depressor, contractile gonadal sheath, and sex-specific muscles. (For more inforamtion, see also Pharynx, Intestine, Rectum and Anus, Male-specific Muscles, Somatic Gonad, Muscle System of the Male and Dauer Pharynx.) In those that contain a single sarcomere, such as pharyngeal, anal depressor, and vulval muscles, the attachment points of the single sarcomere are localized at the ends of the cells as half I bands ending in electron-dense attachments or hemiadherens junctions and connect the myofilaments to epithelium or basal lamina. In other nonstriated muscles where the myofilament network is less well organized, such as uterine muscle um2 and contractile gonadal sheath (see also Egg-laying Apparatus and Somatic Gonad), the filaments seem to be attached to the plasma membrane via randomly localized electron-dense attachments, similar to those found in vertebrate smooth muscle.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1284, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7e9b9c9d-80f0-4e97-9eae-1e115c5f8453": {"__data__": {"id_": "7e9b9c9d-80f0-4e97-9eae-1e115c5f8453", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 2) Pharyngeal Muscles](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "09882b85-5257-4138-97a1-854ae8eae2c8", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 2) Pharyngeal Muscles](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "hash": "5953307aa6a92dc9ef2a19e9c0dbf12b8a16a5b4916bcd2c09592156566e0bb1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "This group is comprised of 20 cells located in eight distinct divisions, pm1\u00e2\u0080\u0093pm8, in the pharynx (MusFIG 17; PharynxAtlas). Each pharyngeal muscle (pm) division contains one to three muscle cells (see Alimentary System - Overview) and each division, except the most posterior one, has threefold radial symmetry. Pharyngeal muscle cells are thought to be myoepithelial because, along with arcade cells, they secrete the pharyngeal cuticle. Also, they have clearly defined apical regions adjacent to the lumen cuticle and are bound by zonula adherens junctions. Contraction of pharyngeal muscle cells in general serves to open the lumen. In the first five layers (pm1\u00e2\u0080\u0093pm5), radially oriented filaments attach medially to the cuticle of the lumen and laterally to the pharyngeal basal lamina by hemiadherens junctions (these are labeled \u00e2\u0080\u009chalf-desmosomes\u00e2\u0080\u009d in Albertson and Thomson, 1976), which are characterized by an electron-dense deposit on the cytoplasmic face of the plasma membrane (Albertson and Thomson, 1976). pm6 has three posterior projections that extend into pm7, and filaments are excluded from the middle one of these projections. pm7 cells contain both radially and longitudinally oriented filaments that provide a longitudinal, aswell as a radial, component to the motion of the grinder teeth when they contract. Similar to pm1\u00e2\u0080\u0093pm5, pm8 has radially oriented filaments that attach to the lumenal cuticle and the pharyngeal basal lamina at their ends. All muscles except pm8 are innervated by pharyngeal motor neurons. pm8 does not receive any direct  innervation from any of the motor neurons. However, pm8 makes gap junctions to mc3 cells, which are innervated by the M5 neuron (Albertson and Thomson, 1976; White, 1988) (see Alimentary System - Overview and Pharynx, see also Gap Junctions).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1817, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f8789ac2-ca2a-4f6c-8363-2fbb340330d8": {"__data__": {"id_": "f8789ac2-ca2a-4f6c-8363-2fbb340330d8", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 3) Stomatointestinal Muscles](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "95488d04-06a5-4775-94ba-4e3f69718908", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 3) Stomatointestinal Muscles](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "hash": "a1f0dff9f6f4425f3988d8d508349a556c7d1608bec04aedc9170c9796b97f7c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Stomatointestinal (SI) muscles are two sheet-like cells that connect the surfaces of the intestinal cells to the ventral body wall (MusFIG 18; MusMOVIE 3) (Bird and Bird, 1991; Avery and Thomas, 1997). Some longitudinally oriented filaments are located in the ventral regions of the cells, and their attachment structures toward the intestine probably resemble the vertebrate smooth muscle as randomly placed along the cell length (White et al., 1986). Thin, flat processes of these cells wrap around the posterior regions of the intestine on the dorsal side. These processes contain a few vertically oriented myofilaments that attach to the dorsal body wall by  hemiadherens junctions, just lateral to the dorsal body wall muscles. The stomatointestinal muscles send muscle arms to preanal ganglion where they receive synaptic input from DVB (direct input) and AVL (indirect input) neurons. They are electrically coupled to the anal sphincter and anal depressor muscles via gap junctions (see also Gap Junctions). Contraction of these muscles promotes defecation by pressurizing the intestinal contents near the posterior end of the intestine (see also Alimentary System - Intestine).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1185, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b621ba73-b2cc-42c6-a2e2-5dbd0470da73": {"__data__": {"id_": "b621ba73-b2cc-42c6-a2e2-5dbd0470da73", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 4) Anal Depressor Muscle](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "973ca797-ffe4-422c-8ada-b00d5cb4ecaf", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 4) Anal Depressor Muscle](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "hash": "ad10bde192fa7ba19d24e0b9de237d211397fd0da057519824c9dd45b9dcc980", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "This is a large, single-sarcomere, H-shaped muscle in hermaphrodites that runs vertically between the dorsal wall of the rectum and the dorsal hypodermis (MusFIG 18 and MusFIG 19) (Thomas, 1990; Avery and Thomas, 1997). This muscle lifts the roof of the rectum when it contracts, allowing the rectum to fill during initial stages of defecation. Later, during defecation it relaxes and the contents of the rectum are expelled (Bird and Bird, 1991). The contractile elements are organized as two parallel sheets of filaments on the right and left sides of this cell, forming two vertically arranged, single sarcomeres. This muscle sends a long muscle arm to the preanal ganglion to be innervated by the DVB (directly) and AVL (indirectly) motor neurons (see also Alimentary System - Intestine).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 792, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "da4b8c83-faf5-46a0-b8a6-1308111b0c35": {"__data__": {"id_": "da4b8c83-faf5-46a0-b8a6-1308111b0c35", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 4) Anal Depressor Muscle](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d5e342ed-8a41-4a03-9538-d02a545f7aa2", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 4) Anal Depressor Muscle](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "hash": "4c589e07dd6d2d1a8055cad8e575654602c579441d69727ce9b8c46952abc583", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "This muscle is sexually dimorphic between hermaphrodite and male. In males, the contractile apparatus of the anal depressor detaches from the dorsal hypodermis and attaches to the dorsal spicule protractor during the L4 molt, completely reorienting the myofilaments to run anteroposteriorly instead of dorsoventrally (Male-specific Muscles) (Sulston and Horvitz, 1977; Sulston et al., 1980; White, 1988).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 404, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c1d97bf4-f933-4a44-bcac-b4b14c027efe": {"__data__": {"id_": "c1d97bf4-f933-4a44-bcac-b4b14c027efe", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 5) Anal Sphincter Muscle](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "29e25c91-9d21-44e0-babb-e7156557f648", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 5) Anal Sphincter Muscle](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "hash": "798a6b91add3c9987467b69f2f243ad5c9889ea0e212e0cbaf136609f98dc898", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "This is a single cell with a toroidal region encircling the proximal part of the rectum and about eight thin processes that radiate  medially and laterally from this toroid. These include four long, filament-filled processes that extend laterally to anchor to the body wall on the dorsal and ventral sides (MusFIG 18 and MusFIG 20). The anal sphincter muscle circles the intestine at its junction with the rectum. During defecation, it is dilated before enteric muscle contractions occur to allow waste material to pass into the rectum. It then contracts nearly simultaneously with the other enteric muscles, possibly helping to squeeze the posterior intestine for expulsion of the waste (Reiner and Thomas, 1995; Avery and Thomas, 1997). The toroidal part of the muscle contains a continuous ring of contractile filaments, many of which do not seem to connect to any significant end-point attachment structures. In this aspect, it is thought to be similar to vertebrate smooth muscle (White, 1988). Filaments within the medially projecting, short processes occasionally show electron-dense attachments to the gland cells at the roof and floor of the rectal passageway (MusFIG 20) (see also Alimentary System - Intestine and Rectum and Anus).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1242, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fa4bb7d0-68c6-45c8-9bdd-0179068a18f0": {"__data__": {"id_": "fa4bb7d0-68c6-45c8-9bdd-0179068a18f0", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 5) Anal Sphincter Muscle](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6cae1dec-27b5-4d47-95a2-6ef676572037", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 5) Anal Sphincter Muscle](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "hash": "13fe85ae6a2538b4178e140471d1b9edb330e5a63c99131495c1078aa2fc4433", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "This muscle is sexually dimorphic between hermaphrodite and male. In males, near the end of the L4 stage the muscle goes under a dramatic hypertrophy during the opening of a cloacal canal. In contrast to hermaphrodites and larval males, this modified sphincter must relax in males to permit defecation (see Male-specific Muscles) (Reiner and Thomas, 1995; Emmons and Sternberg, 1997).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 384, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "df05cdc9-d2db-4b35-9748-c4dc42020972": {"__data__": {"id_": "df05cdc9-d2db-4b35-9748-c4dc42020972", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 6) Vulval Muscles](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "796e2eb1-1e75-4ca3-8b92-642d4df2fca9", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 6) Vulval Muscles](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "hash": "46fe4b9265d260219135dc3cce7e4fc7cb7a1891c0c6c552358d3419b6d5ce82", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The two sets of vulval muscles are vm1 and vm2, and each set contains four muscle cells with single sarcomeres (MusFIG 21). Both vulval and uterine muscles in the hermaphrodite are born at the late-L3 stage from two sex myoblasts, M.vlpaa and M.vrpaa. Through three consecutive divisions, each sex myoblast generates two sets (vm and um) of four daughters, with a total of 16 cells located around the developing vulva by the L3 molt. Eight of these comprise the vulval muscles. The four vm1 muscles insinuate between rows of ventral body wall muscles and run between the dorsal edge of the ventral body wall muscle quadrant and the vulC and vulD toroids of vulva (White et al., 1986). The four vm2 muscles run between the ventral margin of the body wall muscle quadrants and the uterus\u00e2\u0080\u0093vulva junction (between the uterus and vulF toroid). Hence, vm1 cells attach to the vulva more ventrally than do vm2 and are more superficial (Sulston and Horvitz, 1977). The single sarcomeres of each vulval muscle stretch along the entire muscle length and attach through hemiadherens junctions to discrete zones in the body wall on one end and to the vulval epithelium and vulval cuticle on the opposite end around the late-L4 stage (White, 1988). The nuclei of the sex muscles also settle into their final positions around the developing gonad at the L4 stage. Among vulval muscles, the vm2s are the only ones that are directly innervated by the VC and HSN neurons of the egg-laying circuitry. The other muscles are either directly or indirectly connected to vm2 by gap junctions (see also Gap Junctions). vm2s send muscle arms to a local neuropil on either side of the hypodermal ridge to receive synaptic input (White, 1988). Coordinated contraction of the vulval muscles expands the uterus and pulls the vulval lips apart, opening the passage for eggs to be expelled (Hodgkin, 1988) (see also Reproductive System - Egg-laying apparatus). Nematodes missing all eight vulval muscles are unable to lay eggs (Bird and Bird, 1991).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2020, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ed58162c-4e23-40c7-ae42-540363a42749": {"__data__": {"id_": "ed58162c-4e23-40c7-ae42-540363a42749", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 7) Uterine Muscles](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c33be8f8-6d29-4bb5-90b1-e5dd39d95822", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 7) Uterine Muscles](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "hash": "53a567395ee6a86fd8bc18fa62902a8de29743dccdb3da86173f8d10ae860515", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "There are two sets of uterine muscles, um1 and um2, with four post-embryonically born muscle cells in each set. Each um1 cell makes a quarter of a circle that cups the proximal uterus on the ventral side and attaches to it close to the vulva (MusFIG 22). Dorsally, these cells attach to the lateral seam cells close to the utse-seam attachment sites (Vogel and Hedgecock, 2001; Woo et al., 2004). In each half (left and right sides) uterus, the distal sets of uterine muscle cells (um2) make half circles that wrap around the uterus and attach to it in a region further from the vulva (Sulston and Horvitz, 1977). The filaments of the uterine muscles are circumferentially oriented, which, when the muscle contracts, may move eggs through the uterus by a squeezing action (Sulston and Horvitz, 1977). This myofilament network seems to be anchored to the thin basal lamina on the surface facing the uterus by randomly placed attachment points, similar to the distribution of the dense bodies in vertebrate smooth muscles (MusFIG 1D). There is no direct innervation of the uterine muscles. Instead, they are coupled via gap junctions to vulval muscles (White et al., 1986) (see also Reproductive System - Egg-laying apparatus and Gap Junctions). Nematodes missing all eight uterine muscles are still able to lay eggs, as has been shown by ablation studies (Bird and Bird, 1991).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1376, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "29dcee2a-60ef-4ea9-8709-9c5ab6a1bf00": {"__data__": {"id_": "29dcee2a-60ef-4ea9-8709-9c5ab6a1bf00", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 8) Contractile Gonad Sheath of the Hermaphrodite](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "77a7092f-6a26-4e85-8e73-3bf98e1b439c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 8) Contractile Gonad Sheath of the Hermaphrodite](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "hash": "7bf7e472cf696df2932fa79f284621949203678786fdb481ca347882de5367bb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Five pairs of gonadal sheath cells have stereotyped positions along the proximal\u00e2\u0080\u0093distal axis of the gonad and cover the germ-line tissue of each gonadal arm (see MusFIG 17 and Reproductive System - Somatic gonad). Sheath cell pairs 3, 4, and 5 abundantly express muscle filament components such as actin and myosin that are organized into dense networks (Hirsh et al., 1976; Strome, 1986; Goetinck and Waterston, 1994; McCarter et al., 1997; Hall et al., 1999). Filaments are predominantly longitudinally oriented in pairs 3 and 4 and both longitudinally and circumferentially oriented in pair 5 (MusFIG 18). Filaments are also present in sheath cells 1 and 2, but are much less abundant. The myofilament network of the contractile gonadal sheath is possibly similar in organization to that of vertebrate smooth muscle. Anchorage points for the myofilament lattice are distributed diffusely over the outward-facing cell surface. Each connects to the nearby basal lamina by an electron-dense attachment on the plasma membrane. During ovulation, contraction of the proximal sheath pulls the dilated spermatheca over the most proximal oocyte and hence transfers this oocyte into the spermatheca for fertilization. The sheath is not innervated. Instead, it contracts periodically, possibly in response to recurrent intracellular Ca++ transient currents (Bui and Sternberg, 2002, and references therein) (see Reproductive System - Somatic gonad). Gap junctions connect the sheath cells to one another, and transitory gap junctions connect the sheath to the primary oocyte (Hall et al., 1999) (see also Gap Junctions). Thus, signals between the germ line and sheath may coordinate sheath contractions to events in the oocyte and to the presence of sperm (McCarter et al., 1999; Miller et al., 2001; 2003).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1801, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "acc5e97d-5279-48d4-a1d1-c3106cb69b1d": {"__data__": {"id_": "acc5e97d-5279-48d4-a1d1-c3106cb69b1d", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 9) List of Nonstriated Muscle Cells](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a46e6324-f8f1-4bf7-b102-b1eb94731280", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 9) List of Nonstriated Muscle Cells](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "hash": "b000b6316089058a8b7def0a7bc5715e839981cfe3027458869ec6fc4e6da19f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "i. Pharyngeal muscles (pm); Note that in earlier publications these cells are labeled as \"m\"; m1, m2, m3 etc., here they are labeled \"pm\" for \" p haryngeal m uscle\" ( Avery L. and Thomas J. H., 1997 )", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 200, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b18c6566-24b8-4c03-9557-ae9d59f30a8e": {"__data__": {"id_": "b18c6566-24b8-4c03-9557-ae9d59f30a8e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 9) List of Nonstriated Muscle Cells](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "20c282b5-3d44-4600-8f05-3c6dbeb29645", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 9) List of Nonstriated Muscle Cells](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "hash": "497e6627dd2cb4d72f5399aa4bb104b2f2431e488432d8130ff2e08b42453282", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "1. First pharyngeal muscle ring; all fuse into one syncytium around hatching\n\npm1DL\n\npm1DR\n\npm1L\n\npm1R\n\npm1VL\n\npm1VR\n\n2. Second pharyngeal muscle ring\n\npm2DL; fuses with DR around hatching\n\npm2DR; fuses with DL around hatching\n\npm2L; fuses with VL around hatching\n\npm2R; fuses with VR around hatching\n\npm2VL; fuses with L around hatching\n\npm2VR; fuses with R around hatching\n\n3. Third pharyngeal muscle ring\n\npm3DL; fuses with DR around hatching\n\npm3DR; fuses with DL around hatching\n\npm3L; fuses with VL around hatching\n\npm3R; fuses with VR around hatching\n\npm3VL; fuses with L around hatching\n\npm3VR; fuses with R around hatching\n\n4. Fourth pharyngeal muscle ring\n\npm4DL; fuses with DR around hatching\n\npm4DR; fuses with DL around hatching\n\npm4L; fuses with VL around hatching\n\npm4R; fuses with VR around hatching\n\npm4VL; fuses with L around hatching\n\npm4VR; fuses with R around hatching\n\n5.Fifth pharyngeal muscle ring\n\npm5DL; fuses with DR around hatching\n\npm5DR; fuses with DL around hatching\n\npm5L; fuses with VL around hatching\n\npm5R; fuses with VR around hatching\n\npm5VL; fuses with L around hatching\n\npm5VR; fuses with R around hatching\n\n6. Sixth pharyngeal muscle ring\n\npm6D\n\npm6VL\n\npm6VR\n\n7. Seventh pharyngeal muscle ring\n\npm7D\n\npm7VL\n\npm7VR\n\n8. Eighth pharyngeal muscle ring\n\npm8", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1292, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "42ec15e5-1d1c-4a1e-8c7d-a24fafa09f4d": {"__data__": {"id_": "42ec15e5-1d1c-4a1e-8c7d-a24fafa09f4d", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 9) List of Nonstriated Muscle Cells](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "03938141-fcb1-48a1-b785-285cf23be36b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 9) List of Nonstriated Muscle Cells](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "hash": "aa66ee5e489ed344391ebecdb9b1e4d1c87cbbc6a51b41595ebc49dea34a37c3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "ii. Enteric muscles", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 19, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "241643bc-f82c-479d-a325-98df004f49cd": {"__data__": {"id_": "241643bc-f82c-479d-a325-98df004f49cd", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 9) List of Nonstriated Muscle Cells](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "13506f17-a36c-4e00-b75c-d554a378eb0a", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 9) List of Nonstriated Muscle Cells](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "hash": "b28f800b8b222d6c62d007df2927c2a2592e8beeaa507c4d4ec78f82e7305fc6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "1. Stomatointestinal muscle\n\nmu intL; ABplpppppaa\n\nmu intR; MSppaapp\n\n2. Anal sphincter muscle \n\nmu sph; ABprpppppap\n\n3. Anal depressor muscle\n\nmu anal; ABplpppppap", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 164, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2cac30f0-5646-485c-a791-01f15f4e11be": {"__data__": {"id_": "2cac30f0-5646-485c-a791-01f15f4e11be", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 9) List of Nonstriated Muscle Cells](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "03d1a3c1-e559-4671-a5a6-19844cff8f79", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 9) List of Nonstriated Muscle Cells](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "hash": "7094fd4f63f660ecbe36df293d074d80049e00cd1da3b34ed500ee95ffb1b846", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "iii. Hermaphrodite sex muscles", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 30, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3be6113c-56d8-4505-a34b-c5f8f3724cd7": {"__data__": {"id_": "3be6113c-56d8-4505-a34b-c5f8f3724cd7", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 9) List of Nonstriated Muscle Cells](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b8196687-5ace-4721-86c2-5fc0863e0638", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 9) List of Nonstriated Muscle Cells](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "hash": "73647719472df43aa6d74ab25423eb264e6a06e4fff132b37693462040ba0adb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "1. vm1\n\nM.vrpaapaa\n\nM.vrpaaapp\n\nM.vlpaapaa\n\nM.vlpaaapp\n\n2. vm2 \n\nM.vrpaapap\n\nM.vrpaaapa\n\nM.vlpaapap\n\nM.vlpaaapa\n\n3. um1 \n\nM.vrpaappa\n\nM.vrpaaaap\n\nM.vlpaappa\n\nM.vlpaaaap\n\n3. um2\n\nM.vrpaappp\n\nM.vrpaaaaa\n\nM.vlpaappp\n\nM.vlpaaaaa", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 224, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "65ebd151-d7ab-49b6-b791-9f63aed126fa": {"__data__": {"id_": "65ebd151-d7ab-49b6-b791-9f63aed126fa", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 9) List of Nonstriated Muscle Cells](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "da7b17cb-d8df-4373-8c3a-18a97e841646", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 9) List of Nonstriated Muscle Cells](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "hash": "ae8733cac2b0ff8e6544a28fca015ea0a1d72f677bc9b5947677f15d1c1ceb00", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "iv. Hermaphrodite contractile gonadal sheath", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 44, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b86def58-a3af-4dda-8243-4d12dd75c745": {"__data__": {"id_": "b86def58-a3af-4dda-8243-4d12dd75c745", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 9) List of Nonstriated Muscle Cells](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "78c0c640-f598-4642-9140-fba6256929e3", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 9) List of Nonstriated Muscle Cells](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "hash": "99088efdaa1fa747637ae2898ad3542418d08d40ee8fb97791ab847cb3aa4452", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "1. Somatic Sheath (10 cells/5 pairs) of anterior gonad arm: Z1.apa (sheath cell 1) \n\nZ1.appaaa (sheath cell 2) \n\nZ1.appaap (sheath cell 3) \n\nZ1.appapa (sheath cell 4) \n\nZ1.appapp (sheath cell 5) \n\nZ1.paaa (sheath cell 1) \n\nZ1.paapaaa (sheath cell 2) \n\nZ1.paapaap (sheath cell 3) \n\nZ1.paapapa (sheath cell 4) \n\nZ1.paapapp (sheath cell 5)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 336, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "60e4edd0-f1ce-41cc-b3d8-0fdc14bee024": {"__data__": {"id_": "60e4edd0-f1ce-41cc-b3d8-0fdc14bee024", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 9) List of Nonstriated Muscle Cells](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "981489bb-42f6-4713-8793-a355a45d74d7", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nonstriated Muscle, Section 9) List of Nonstriated Muscle Cells](https://www.wormatlas.org/hermaphrodite/musclenonstriated/MusNonstriframeset.html)"}, "hash": "15a3edc657e72fed3430b83094b6745c5a81e7a5d417958c8be811eb71b0b8e9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "2. Somatic Sheath (10 cells/5 pairs) of posterior gonad arm: Z4.pap (sheath cell 1) \n\nZ4.paappp (sheath cell 2) \n\nZ4.paappa (sheath cell 3) \n\nZ4.paapap (sheath cell 4) \n\nZ4.paapaa (sheath cell 5) \n\nZ4.appp (sheath cell 1) \n\nZ4.appappp (sheath cell 2) \n\nZ4.appappa (sheath cell 3) \n\nZ4.appapap (sheath cell 4) \n\nZ4.appapaa (sheath cell 5)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 337, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "91f54ae9-d8fd-4f4c-8ce1-faaee473b1b4": {"__data__": {"id_": "91f54ae9-d8fd-4f4c-8ce1-faaee473b1b4", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4ad17d2e-5b68-441e-98e4-abba2549322c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "6ae1a143bc01e3f71b9df11697a9399e4a4c4dc9e8dbacc0d1d94772afe4522c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "ADAL is a neuron in the worm C. elegans, of type Layer 3 interneuron. The name stands for Anterior Process from Deirid Commissure A Left. ADAL is a Ring interneuron. The cell lineage of ADAL is AB plapaaaapp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 208, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ad75dced-9374-44a3-8370-940e67d8f196": {"__data__": {"id_": "ad75dced-9374-44a3-8370-940e67d8f196", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "266f281d-79b7-44e8-bd2d-9b3869c08010", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "a284dfea64e3f8132ee8ffd087c6db805b6802b9a320fb68620c4c5544212ef6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "ADAR is a neuron in the worm C. elegans, of type Layer 3 interneuron. The name stands for Anterior Process from Deirid Commissure A Right. ADAR is a Ring interneuron. The cell lineage of ADAR is AB prapaaaapp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 209, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d3bd4b48-5848-400d-8b9d-6212029af2eb": {"__data__": {"id_": "d3bd4b48-5848-400d-8b9d-6212029af2eb", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "07783e29-d74c-4c50-825f-f96c8fb43a96", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "297c6c3af4f40ea2749bc45ca1c1484b95726e4dfafaf0a6e52194dcee9ee304", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "ADEL is a neuron in the worm C. elegans, of type Mechanosensory. The name stands for Anterior DEirid Neuron Left. ADEL is a Anterior deirid, sensory neuron. The cell lineage of ADEL is AB plapaaaapa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 199, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b6bb46c9-cbdb-427b-920f-3d822949d5bf": {"__data__": {"id_": "b6bb46c9-cbdb-427b-920f-3d822949d5bf", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "db91567a-ad2b-4153-96ba-300c635dbc4f", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "7d6d4280d36f2cfdffda6beb6274e827ded4f7218a0c737b525e1724a22f7f16", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "ADER is a neuron in the worm C. elegans, of type Mechanosensory. The name stands for Anterior DEirid Neuron Right. ADER is a Anterior deirid, sensory neuron. The cell lineage of ADER is AB prapaaaapa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 200, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c4200ac2-5200-4750-a44d-66b2cd4db974": {"__data__": {"id_": "c4200ac2-5200-4750-a44d-66b2cd4db974", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "42a9e057-7c0f-4aa8-b1bd-e2fd51e6f170", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "5f4a3774ee4e48aaca4abfe65cd3891f252a52b8912aca0b6c95c907804fd6ac", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "ADFL is a neuron in the worm C. elegans, of type Amphid. The name stands for Amphid Dual Ciliated Ending F Left. ADFL is a Amphid neuron. The cell lineage of ADFL is AB alpppppaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 179, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b707921c-1e54-4dc5-b4b0-21b70c3dd3fe": {"__data__": {"id_": "b707921c-1e54-4dc5-b4b0-21b70c3dd3fe", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1b529ff1-82e5-4639-9679-d85ae9fcfc63", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "18f850cf3e951fb3f131c18b9be7e1797a5d076a735864444b434bc9791b472f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "ADFR is a neuron in the worm C. elegans, of type Amphid. The name stands for Amphid Dual Ciliated Ending F Right. ADFR is a Amphid neuron. The cell lineage of ADFR is AB praaappaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 180, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "17657ac5-8a27-4a69-a838-e980a1780a34": {"__data__": {"id_": "17657ac5-8a27-4a69-a838-e980a1780a34", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a997eee3-aba5-4e4a-a5e8-f0b961530c93", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "536824e4eed06840855679c8ce3035614f25191515dc16225bb2b99a7029db56", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "ADLL is a neuron in the worm C. elegans, of type Amphid, nociceptive. The name stands for Amphid Dual Ciliated Ending L Left. ADLL is a Amphid neuron. The cell lineage of ADLL is AB alppppaad.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 192, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fd76aab7-e189-456b-a5c0-16d77196fc1f": {"__data__": {"id_": "fd76aab7-e189-456b-a5c0-16d77196fc1f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ed4fdf75-7fe0-4ea8-8b71-3fe9e2d5aac8", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "015290f2c43cc4c36fdd2318bf454c989cb66b1b23ee0008422edba4cdf235ae", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "ADLR is a neuron in the worm C. elegans, of type Amphid, nociceptive. The name stands for Amphid Dual Ciliated Ending L Right. ADLR is a Amphid neuron. The cell lineage of ADLR is AB praaapaad.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 193, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6f3b3eb2-fb68-4ee8-8a58-056daf04d268": {"__data__": {"id_": "6f3b3eb2-fb68-4ee8-8a58-056daf04d268", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7af6fc5c-ecff-46df-a040-596e28c06d42", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "1e78ddb496960324659654ebb9933c32f4793bd51b1b578424a55c96f058b704", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AFDL is a neuron in the worm C. elegans, of type Amphid. The name stands for Amphid Finger-like Endings D Left. AFDL is a Amphid finger cell. The cell lineage of AFDL is AB alpppapav.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 183, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "afc1f3de-9e0c-4b1b-a4b3-403eeaec87d2": {"__data__": {"id_": "afc1f3de-9e0c-4b1b-a4b3-403eeaec87d2", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2425da4c-8c24-4218-a766-af243ccd9bf8", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "93427d3f09c19a7b7392e823ec438dcb4f9d7255701187c3eb95a89a30e05c85", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AFDR is a neuron in the worm C. elegans, of type Amphid. The name stands for Amphid Finger-like Endings D Right. AFDR is a Amphid finger cell. The cell lineage of AFDR is AB praaaapav.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 184, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "422c9663-481b-4f1e-a114-03aabdff61e5": {"__data__": {"id_": "422c9663-481b-4f1e-a114-03aabdff61e5", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "17c47c69-4032-4c33-99a5-7b95ac1996e7", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "37072c96aea96904c0ac51d172cd0f760b5d26c80cda9f4a9f58a20deea7eba2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AIAL is a neuron in the worm C. elegans, of type Layer 3 interneuron. The name stands for Anterior Interneuron A Left. AIAL is a Amphid interneuron. The cell lineage of AIAL is AB plppaappa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 190, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e7ced9e3-c3e8-43b0-8fb9-11b5837e54e0": {"__data__": {"id_": "e7ced9e3-c3e8-43b0-8fb9-11b5837e54e0", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "afbf714c-9d81-4382-8b92-dba0caf2aeac", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "0843802f1b761311ee2c2d8959dc029517e8223773417d5b9a47aee37c0aca3f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AIAR is a neuron in the worm C. elegans, of type Layer 3 interneuron. The name stands for Anterior Interneuron A Right. AIAR is a Amphid interneuron. The cell lineage of AIAR is AB prppaappa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 191, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d475f0a5-f785-4f46-a479-ea29b598d1dd": {"__data__": {"id_": "d475f0a5-f785-4f46-a479-ea29b598d1dd", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3c232d79-bb01-49d5-afe2-220faf11caa1", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "6a11e66c2dc15e312b7d15dc62143df73d3bafee205540e13614991dca881882", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AIBL is a neuron in the worm C. elegans, of type Layer 2 interneuron. The name stands for Anterior Interneuron B Left. AIBL is a Amphid interneuron. The cell lineage of AIBL is AB plaapappa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 190, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f33054d2-ebbf-4cb6-9cda-f81422665a2e": {"__data__": {"id_": "f33054d2-ebbf-4cb6-9cda-f81422665a2e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c6201713-740b-4107-a100-033a092c274e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "0a7727f2e1aaaa08a7ada73e81204b43f46181cbf5f42ff148e1a33129744e94", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AIBR is a neuron in the worm C. elegans, of type Layer 2 interneuron. The name stands for Anterior Interneuron B Right. AIBR is a Amphid interneuron. The cell lineage of AIBR is AB praapappa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 191, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9e815d10-98b9-49cc-8ed6-28d2def41eff": {"__data__": {"id_": "9e815d10-98b9-49cc-8ed6-28d2def41eff", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "55867e79-9407-44da-a952-7f3d278e44dd", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "07e65b72e336e4e359ab657633ebd510266570bfc06c0eb56e3ccc7eb0df4092", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AIML is a neuron in the worm C. elegans, of type Category 4 interneuron. The name stands for Anterior Interneuron M Left. AIML is a Ring interneuron. The cell lineage of AIML is AB plpaapppa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 191, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "949db34a-e84a-41e9-9946-71f8af04d425": {"__data__": {"id_": "949db34a-e84a-41e9-9946-71f8af04d425", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2ef14ab8-e984-420c-8ce8-f3bddf5a00b3", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "e1029ceb0a601c4a22443fd58e58f487cd89c8fe9e55c1284a087216aca814cf", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AIMR is a neuron in the worm C. elegans, of type Category 4 interneuron. The name stands for Anterior Interneuron M Right. AIMR is a Ring interneuron. The cell lineage of AIMR is AB prpaapppa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 192, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "98570186-60bc-49f5-ba35-6105f4e667f3": {"__data__": {"id_": "98570186-60bc-49f5-ba35-6105f4e667f3", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "65557451-c00e-4c31-aab5-99f0b9bd8210", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "d08ba001cb90818209cf1eb2ce15080b781b4b0355c111c6a6b8bdc6cf748142", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AINL is a neuron in the worm C. elegans, of type Category 4 interneuron. The name stands for Anterior Interneuron N Left. AINL is a Ring interneuron. The cell lineage of AINL is AB alaaaalal.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 191, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "edd82489-51a6-4e61-afe8-3c5d5471e200": {"__data__": {"id_": "edd82489-51a6-4e61-afe8-3c5d5471e200", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "23aa33fc-ebf3-40a4-beb9-8baa4bcc60b5", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "8397cb0fd466630c97b53f949682f6dc3a3d8f87c38b772544ab36c331a7ae6c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AINR is a neuron in the worm C. elegans, of type Category 4 interneuron. The name stands for Anterior Interneuron N Right. AINR is a Ring interneuron. The cell lineage of AINR is AB alaapaaar.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 192, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ce06de27-eba0-4bc7-b7b0-c28e335a64c8": {"__data__": {"id_": "ce06de27-eba0-4bc7-b7b0-c28e335a64c8", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "759479cf-c341-45d4-ab86-d4535496b0bb", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "a318e29062d39ac5bf28c55614216ac6555a016f11dfc30ecbd0b1da46a9124d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AIYL is a neuron in the worm C. elegans, of type Layer 3 interneuron. The name stands for Anterior Interneuron Y Left. AIYL is a Amphid interneuron. The cell lineage of AIYL is AB plpapaaap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 190, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0b55da3c-25f9-453d-aa63-3217b1186ae2": {"__data__": {"id_": "0b55da3c-25f9-453d-aa63-3217b1186ae2", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2bfa9f4d-995e-4250-b2e8-bf44495079cf", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "0fbeec55647dfeff4033fb35fee3941e1c35b58ade8fcd03da1fca1c3e995cb5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AIYR is a neuron in the worm C. elegans, of type Layer 3 interneuron. The name stands for Anterior Interneuron Y Right. AIYR is a Amphid interneuron. The cell lineage of AIYR is AB prpapaaap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 191, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "13417ed5-a352-4ec9-ac35-bcc0945b1e4f": {"__data__": {"id_": "13417ed5-a352-4ec9-ac35-bcc0945b1e4f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "59523654-ce0a-468f-9cb7-bbbd1a98f0d2", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "a14b6351ae06e3e06e44153527c95f9e40ce458931d9b6d413ba68ccd3a8c3f6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AIZL is a neuron in the worm C. elegans, of type Layer 3 interneuron. The name stands for Anterior Interneuron Z Left. AIZL is a Amphid interneuron. The cell lineage of AIZL is AB plapaaapav.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 191, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e17a940c-672e-4f6c-9bd5-ced0b1f2a394": {"__data__": {"id_": "e17a940c-672e-4f6c-9bd5-ced0b1f2a394", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4b053243-dad0-47e5-8ef8-2bd8d1516613", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "2d1fcc04c96720d5ca17a1565537b3ac315409452bd86af010e35a5d227cdc50", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AIZR is a neuron in the worm C. elegans, of type Layer 3 interneuron. The name stands for Anterior Interneuron Z Right. AIZR is a Amphid interneuron. The cell lineage of AIZR is AB prapaaapav.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 192, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f858b989-ae61-401f-acd0-492cd52bd6fa": {"__data__": {"id_": "f858b989-ae61-401f-acd0-492cd52bd6fa", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3a2b0d1e-6b8a-43d6-849b-961c11eb02d3", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "9c73f14aaf7644bb30099407b77edcacdf81ac79ec6cdbef510d70e3fb55484e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "ALA is a neuron in the worm C. elegans, of type Layer 3 interneuron. The name stands for Anterior Lateral Neuron A. ALA is a Neuron, sends processes laterally and along dorsal cord. The cell lineage of ALA is AB alapppaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 222, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "28b45eb9-cf7a-4dcf-bb76-e564fdc50bea": {"__data__": {"id_": "28b45eb9-cf7a-4dcf-bb76-e564fdc50bea", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8fe950a9-6ad9-46c2-9237-555755618b86", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "d451397c528c723a8e200eec528deba0b6086839d9610a36645a0a3e4cedf5ba", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "ALML is a neuron in the worm C. elegans, of type Mechanosensory. The name stands for Anterior Lateral Microtubule Neuron Left. ALML is a Anterior lateral microtubule cell. The cell lineage of ALML is AB arppaappa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 213, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "77b372be-e426-48c9-bd83-06ab491162cc": {"__data__": {"id_": "77b372be-e426-48c9-bd83-06ab491162cc", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "73da1170-d5ee-4000-853a-bb85d473d78f", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "849fb69124e5e55d90c02f854135f978733163e58d8d0b6ac6b64803ee58f1b0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "ALMR is a neuron in the worm C. elegans, of type Mechanosensory. The name stands for Anterior Lateral Microtubule Neuron Right. ALMR is a Anterior lateral microtubule cell. The cell lineage of ALMR is AB arpppappa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 214, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c14a6e4a-0497-49e9-8060-fbdc435b6072": {"__data__": {"id_": "c14a6e4a-0497-49e9-8060-fbdc435b6072", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6b4dbcdc-9533-4760-ab03-fa0eb0edc846", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "c5c43699a8bd366f8ff48a37dc4f624ffece02b8d1b51e866847abaa68baddfd", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "ALNL is a neuron in the worm C. elegans, of type Touch. The name stands for Anterior Lateral Neuron N Left. ALNL is a Neuron associated with ALM. The cell lineage of ALNL is AB plapappppap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 189, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3ee1a8f0-0a1a-46ab-bc63-4f73ed17d77f": {"__data__": {"id_": "3ee1a8f0-0a1a-46ab-bc63-4f73ed17d77f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ec342c0c-8857-4b5d-844e-b91d3503959a", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "44ee9503a3f95f1703cbf922e72be43fbc0480a43da5b82a8fd8d03fc55d27d5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "ALNR is a neuron in the worm C. elegans, of type Touch. The name stands for Anterior Lateral Neuron N Right. ALNR is a Neuron associated with ALM. The cell lineage of ALNR is AB prapappppap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 190, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7babd865-6c9c-4ffb-9529-3ed96d388fa4": {"__data__": {"id_": "7babd865-6c9c-4ffb-9529-3ed96d388fa4", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7e57a171-e12c-4c34-a72d-4b145933a8cb", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "2d8eadbc351a430213bae44ce3d11ae8dbabbea6b21faed69ab6020cf8402e40", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AQR is a neuron in the worm C. elegans, of type Touch. The name stands for Anterior, Q-cell Derived Receptor. AQR is a Neuron, basal body. Not part of a sensillum, projects into ring. The cell lineage of AQR is QR.ap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 217, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f6b0d963-c636-4a05-8584-f9f94c9ad345": {"__data__": {"id_": "f6b0d963-c636-4a05-8584-f9f94c9ad345", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "753c369e-a010-4d86-80d8-a346aef3f671", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "c3811fb0d392aae58da6a942a8efb54133cb7d9b76a8edafd700a3ce02d57eeb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AS1 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for A-type Short Motor Neuron 1. AS1 is a Ventral cord motor neuron, innervates dorsal muscles, no ventral counterpart. The cell lineage of AS1 is P1.apa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 245, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8c8c45b1-244a-4413-9d46-7df65362341a": {"__data__": {"id_": "8c8c45b1-244a-4413-9d46-7df65362341a", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f9e0f8ff-6f11-40da-9190-c0e9069133b8", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "7fbd8b303f0bd4d99e3b051f66d144e43037d8355fa16da1964b2e3d30aff8fb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AS10 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for A-type Short Motor Neuron 10. AS10 is a Ventral cord motor neuron, innervates dorsal muscles, no ventral counterpart. The cell lineage of AS10 is P10.apa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 250, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "44203480-72da-4a97-b815-4f60f11942f4": {"__data__": {"id_": "44203480-72da-4a97-b815-4f60f11942f4", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4ec2972e-bf57-4806-9f02-68ca161c15bb", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "ea68513df6b1f4889940938aa46f14babc345a1cd67635a5f475ca1ee3f08234", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AS11 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for A-type Short Motor Neuron 11. AS11 is a Ventral cord motor neuron, innervates dorsal muscles, no ventral counterpart. The cell lineage of AS11 is P11.apa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 250, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4d930ff7-0c59-46c3-a37a-fc7ab85c8378": {"__data__": {"id_": "4d930ff7-0c59-46c3-a37a-fc7ab85c8378", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "685cc32a-97ac-4612-8121-fc71d315b4f6", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "612653ef2eddf319005d50accef585f69ed42b0a03ca982cc9153ec711f33259", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AS2 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for A-type Short Motor Neuron 2. AS2 is a Ventral cord motor neuron, innervates dorsal muscles, no ventral counterpart. The cell lineage of AS2 is P2.apa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 245, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "16cd225e-1b50-4b0c-aa44-2553e22c9573": {"__data__": {"id_": "16cd225e-1b50-4b0c-aa44-2553e22c9573", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2afa5c92-d407-4f21-aec3-dc83c664b8de", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "1dbd5d234975708f15ef5a62a06e1fc40ea210b9434d5cb5b045266df0f7a237", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AS3 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for A-type Short Motor Neuron 3. AS3 is a Ventral cord motor neuron, innervates dorsal muscles, no ventral counterpart. The cell lineage of AS3 is P3.apa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 245, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ce4decac-e30a-49e6-b1c6-96081b100fa0": {"__data__": {"id_": "ce4decac-e30a-49e6-b1c6-96081b100fa0", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7cfab41b-7a16-47c4-bab8-1bbbec3b5042", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "812995f4db78935daa843b96eef50f53a48de7bd8711f0320ae4902b46165f91", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AS4 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for A-type Short Motor Neuron 4. AS4 is a Ventral cord motor neuron, innervates dorsal muscles, no ventral counterpart. The cell lineage of AS4 is P4.apa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 245, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7ee0fda9-0108-40e1-8f19-0169c1eb2dd7": {"__data__": {"id_": "7ee0fda9-0108-40e1-8f19-0169c1eb2dd7", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9829f162-c74f-466c-b16b-af266cfdd8d8", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "411c3c884b13c0eb3a32364a60cb5e0f0d7ba89bfd1b9da0cff37caf192f75b4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AS5 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for A-type Short Motor Neuron 5. AS5 is a Ventral cord motor neuron, innervates dorsal muscles, no ventral counterpart. The cell lineage of AS5 is P5.apa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 245, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4046ecb2-0685-48f4-a448-51aa6044991d": {"__data__": {"id_": "4046ecb2-0685-48f4-a448-51aa6044991d", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "802f5bfc-fbd6-4a03-a33b-40eb9cfaa8c2", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "8a25155146e4a42f47fd86bbb1000de318c3ac79cf66b2494beb7de673a82238", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AS6 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for A-type Short Motor Neuron 6. AS6 is a Ventral cord motor neuron, innervates dorsal muscles, no ventral counterpart. The cell lineage of AS6 is P6.apa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 245, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "aa4a83ef-df13-4adf-b6e1-2d4b51477875": {"__data__": {"id_": "aa4a83ef-df13-4adf-b6e1-2d4b51477875", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6e4df4e4-85d4-4476-8981-d9480f915221", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "774ab30ff47d57f12dd34ea1174ceed338bdf8946ee4d7bc98038db4dbef6490", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AS7 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for A-type Short Motor Neuron 7. AS7 is a Ventral cord motor neuron, innervates dorsal muscles, no ventral counterpart. The cell lineage of AS7 is P7.apa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 245, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8fbcfd94-18f9-4a97-a113-e39b26d2c916": {"__data__": {"id_": "8fbcfd94-18f9-4a97-a113-e39b26d2c916", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "224040a0-b84c-4ea3-9fce-0859b6c189de", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "f491e4e7193a9211e3bd8c3bac4db758df2fa75e602e0dc46cb74a67fad8b229", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AS8 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for A-type Short Motor Neuron 8. AS8 is a Ventral cord motor neuron, innervates dorsal muscles, no ventral counterpart. The cell lineage of AS8 is P8.apa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 245, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d3c65c5f-d626-40d5-9a5f-44e23739fbb2": {"__data__": {"id_": "d3c65c5f-d626-40d5-9a5f-44e23739fbb2", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4b322baf-e608-4a6d-873f-13fd3d89dcb0", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "11c7fc993d3ea25a8ffe64eabe22c1c8a83b9548172329de02a21b2f4d3be8d5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AS9 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for A-type Short Motor Neuron 9. AS9 is a Ventral cord motor neuron, innervates dorsal muscles, no ventral counterpart. The cell lineage of AS9 is P9.apa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 245, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5c4eb4a1-b982-4b45-9da1-55b21fc5b24c": {"__data__": {"id_": "5c4eb4a1-b982-4b45-9da1-55b21fc5b24c", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b80e7546-a44d-41bf-962f-712f302044a1", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "4ef8d8c393d6cd90f1e61d153f373fc38abd36030a3a73f0d24e98ef0e5cd284", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "ASEL is a neuron in the worm C. elegans, of type Amphid. The name stands for Amphid Single Cilium E Left. ASEL is a Amphid neurons, single ciliated endings. The cell lineage of ASEL is AB alppppppaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 199, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2207a6b8-f941-4f9b-939b-5f03a49b836a": {"__data__": {"id_": "2207a6b8-f941-4f9b-939b-5f03a49b836a", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "062a5ef5-a2ee-4270-99e6-8e750e7ba266", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "90fc28709361faf585cb4de5e802f70958d9ff583334439e7c6f00093c02dcca", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "ASER is a neuron in the worm C. elegans, of type Amphid. The name stands for Amphid Single Cilium E Right. ASER is a Amphid neurons, single ciliated endings. The cell lineage of ASER is AB praaapppaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 200, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c775b269-4850-466b-9351-c7e6e77de33b": {"__data__": {"id_": "c775b269-4850-466b-9351-c7e6e77de33b", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "75ebe9dc-169a-4012-a12c-182c0fe123a4", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "70aec51ef783a56eeca689f02c20ca3dee2780b80d8ffce1fbf4a6797422872d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "ASGL is a neuron in the worm C. elegans, of type Amphid. The name stands for Amphid Single Cilium G Left. ASGL is a Amphid neurons, single ciliated endings. The cell lineage of ASGL is AB plaapapap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 198, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "137e7911-8ee1-4106-917e-1a684401af15": {"__data__": {"id_": "137e7911-8ee1-4106-917e-1a684401af15", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "96f554e4-6a4c-4d33-a588-b44323e4686b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "6edc48f4f645136e06f35d9bc30ab2995ce33ee560a7f17d55b9a7fbdae1e955", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "ASGR is a neuron in the worm C. elegans, of type Amphid. The name stands for Amphid Single Cilium G Right. ASGR is a Amphid neurons, single ciliated endings. The cell lineage of ASGR is AB praapapap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 199, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "81f2a839-3b4a-4cdb-a93f-b6b2e52b7d90": {"__data__": {"id_": "81f2a839-3b4a-4cdb-a93f-b6b2e52b7d90", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7ca85953-49bd-4815-a3cd-0713f8a82181", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "41b05b174a2a5e79a077a2f140e5208c118708ed56421d93fbbb6512e5844e79", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "ASHL is a neuron in the worm C. elegans, of type Amphid, nociceptive. The name stands for Amphid Single Cilium H Left. ASHL is a Amphid neurons, single ciliated endings. The cell lineage of ASHL is AB plpaappaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 211, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0974851d-2ebb-4eb0-a867-f02b38c8a823": {"__data__": {"id_": "0974851d-2ebb-4eb0-a867-f02b38c8a823", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "58e88ecc-ab17-4209-a5b0-3ada3783ab50", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "08a19168a30ee71ece1a0c7475071a99df8c6ff7961da20d1ddf8b90fc89a0b2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "ASHR is a neuron in the worm C. elegans, of type Amphid, nociceptive. The name stands for Amphid Single Cilium H Right. ASHR is a Amphid neurons, single ciliated endings. The cell lineage of ASHR is AB prpaappaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 212, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e8d9f985-4908-47a1-a710-a5832cf99ed1": {"__data__": {"id_": "e8d9f985-4908-47a1-a710-a5832cf99ed1", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0d9219c3-802e-4fbb-9f03-f4d3f14c10f7", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "8dbaedf92d0eff1676b6ce1afb1df4fdb39b9f6b96f2630427679b3d445eeb68", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "ASIL is a neuron in the worm C. elegans, of type Amphid. The name stands for Amphid Single Cilium I Left. ASIL is a Amphid neurons, single ciliated endings. The cell lineage of ASIL is AB plaapapppa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 199, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "360abf2b-4d51-443c-aa97-efefa9152fbf": {"__data__": {"id_": "360abf2b-4d51-443c-aa97-efefa9152fbf", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e9b1efcd-e6d7-4437-bfc9-77288f5a32e3", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "a505d945ff0ccfbdf7e362fcb821c4e5275f1d39e4c273dd9d76a902a8a0672b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "ASIR is a neuron in the worm C. elegans, of type Amphid. The name stands for Amphid Single Cilium I Right. ASIR is a Amphid neurons, single ciliated endings. The cell lineage of ASIR is AB praapapppa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 200, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6d28f756-2da3-4450-a6d6-e654bf804c46": {"__data__": {"id_": "6d28f756-2da3-4450-a6d6-e654bf804c46", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9e5a44bb-248d-4e78-bbe4-2d0cf2521dd1", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "2a80189389e3ae0e0bd47c01a717d382977ea44588a6c522776bcd8fc18ea5a8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "ASJL is a neuron in the worm C. elegans, of type Amphid. The name stands for Amphid Single Cilium J Left. ASJL is a Amphid neurons, single ciliated endings. The cell lineage of ASJL is AB alpppppppa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 199, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "bcd1b4b7-f2a8-44c5-9157-3aa5d1915692": {"__data__": {"id_": "bcd1b4b7-f2a8-44c5-9157-3aa5d1915692", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9ca8bc44-2011-4a4f-9f87-6cb1bb76a444", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "0e68ea44f2e3461ead38376ebd96292e60cded88dc2f0d8785cf40c867603a90", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "ASJR is a neuron in the worm C. elegans, of type Amphid. The name stands for Amphid Single Cilium J Right. ASJR is a Amphid neurons, single ciliated endings. The cell lineage of ASJR is AB praaappppa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 200, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a2b795f2-7043-4e0b-929c-4c60ee0ec697": {"__data__": {"id_": "a2b795f2-7043-4e0b-929c-4c60ee0ec697", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a9fb23d8-16fd-49b2-ae94-79e74bc4052f", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "c456be60f8a98ff03ce0db114ca703672ad11154fd4603214c7564a644f08a75", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "ASKL is a neuron in the worm C. elegans, of type Amphid. The name stands for Amphid Single Cilium K Left. ASKL is a Amphid neurons, single ciliated endings. The cell lineage of ASKL is AB alpppapppa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 199, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6bbfe271-045f-4d3e-b258-ab401807f1ae": {"__data__": {"id_": "6bbfe271-045f-4d3e-b258-ab401807f1ae", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fee24d34-8250-472c-8d6a-bd672f6cdeb6", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "561b1d2c7da437e3d68e77d9fc7c643dee2f9f04625489caa5df49eaa8ccf46f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "ASKR is a neuron in the worm C. elegans, of type Amphid. The name stands for Amphid Single Cilium K Right. ASKR is a Amphid neurons, single ciliated endings. The cell lineage of ASKR is AB praaaapppa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 200, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2729f895-397b-439d-b8ea-653bb07cdda1": {"__data__": {"id_": "2729f895-397b-439d-b8ea-653bb07cdda1", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2c2ca576-003f-4dce-8031-46d681da70e6", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "45c268a86b11e9890cfe1a9309831cffcbf97191c4020c298fd56eeaefc88369", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AUAL is a neuron in the worm C. elegans, of type Layer 3 interneuron. The name stands for Amphid-associated Unknown Receptor A Left. AUAL is a Neuron, process runs with amphid processes but lacks ciliated ending. The cell lineage of AUAL is AB alpppppppp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 255, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0baba5a3-8ac8-42ff-9b9b-1790849ce7fb": {"__data__": {"id_": "0baba5a3-8ac8-42ff-9b9b-1790849ce7fb", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0cf04ac5-b1d7-43a0-9270-21c78838f66f", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "f1412979e7ba935685f9269b8fff3fdbe311c07005a096c08ef3e2b64b14b4f2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AUAR is a neuron in the worm C. elegans, of type Layer 3 interneuron. The name stands for Amphid-associated Unknown Receptor A Right. AUAR is a Neuron, process runs with amphid processes but lacks ciliated ending. The cell lineage of AUAR is AB praaappppp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 256, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "120c7cf4-05b6-4604-8c6d-cafe1f34de13": {"__data__": {"id_": "120c7cf4-05b6-4604-8c6d-cafe1f34de13", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "993c2fb5-7a47-4fd8-b68f-de3033abf533", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "9a438f39d6f72ed63ddb3836bbedb48de21239217f808e35339300aeafd0b781", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AVAL is a neuron in the worm C. elegans, of type Layer 1 interneuron. The name stands for Anterior Ventral Process A Left. AVAL is a Ventral cord interneuron. The cell lineage of AVAL is AB alppaaapa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 200, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9c2e58d9-f562-4a00-b005-8ee4b553c1fe": {"__data__": {"id_": "9c2e58d9-f562-4a00-b005-8ee4b553c1fe", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5ce13d69-72c4-4a01-b361-acc4bc1be9a4", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "755ce5eda71704376fe590648adb6e6afe937abebd872e997dd31e83707b026b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AVAR is a neuron in the worm C. elegans, of type Layer 1 interneuron. The name stands for Anterior Ventral Process A Right. AVAR is a Ventral cord interneuron. The cell lineage of AVAR is AB alaappapa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 201, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3bb9afa8-eaf8-4cb5-88a2-b105faa95978": {"__data__": {"id_": "3bb9afa8-eaf8-4cb5-88a2-b105faa95978", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1d1a199c-293a-48b9-95e3-9988de685f67", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "cb0cda00a70e7e0224ea9aef85e41c81b7fb858cad4521739f100ba2ab0e42a5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AVBL is a neuron in the worm C. elegans, of type Layer 1 interneuron. The name stands for Anterior Ventral Process B Left. AVBL is a Ventral cord interneuron. The cell lineage of AVBL is AB plpaapaap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 200, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "44f5b609-a44d-4862-a49e-6b2aca35ac68": {"__data__": {"id_": "44f5b609-a44d-4862-a49e-6b2aca35ac68", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "32b3e805-11c3-4c05-9f97-9c3502c981af", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "87aa20576c072505945334d633000722dc00311aa05f722865030a140b52975f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AVBR is a neuron in the worm C. elegans, of type Layer 1 interneuron. The name stands for Anterior Ventral Process B Right. AVBR is a Ventral cord interneuron. The cell lineage of AVBR is AB prpaapaap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 201, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6a006b7f-f63f-471c-b2ca-d17f919e09f0": {"__data__": {"id_": "6a006b7f-f63f-471c-b2ca-d17f919e09f0", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7cb67f61-8a20-4bba-9e7f-7031707e9775", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "137c74cb61d80cefef7c3c96ddbde9f5e45c1aa19fb0573eec465d114571f33f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AVDL is a neuron in the worm C. elegans, of type Layer 2 interneuron. The name stands for Anterior Ventral Process D Left. AVDL is a Ventral cord interneuron. The cell lineage of AVDL is AB alaaapalr.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 200, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f36818a7-1a19-4da5-9c57-a192dab2284b": {"__data__": {"id_": "f36818a7-1a19-4da5-9c57-a192dab2284b", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "94e70e96-c68e-4605-b49b-6f19431099d0", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "d75d43433d0ebf5fa383fb36080f105e700eb9af949c84253a52dca56a181521", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AVDR is a neuron in the worm C. elegans, of type Layer 2 interneuron. The name stands for Anterior Ventral Process D Right. AVDR is a Ventral cord interneuron. The cell lineage of AVDR is AB alaaapprl.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 201, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "21feb256-c4b1-49da-b24a-3caac67c96cb": {"__data__": {"id_": "21feb256-c4b1-49da-b24a-3caac67c96cb", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9d8ec630-ed1a-4cf1-b384-0e6b50a9d892", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "7b7453248e199962a1cb7614d0bb74ead1dedada36bf2ca571029f3d6ba499dc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AVEL is a neuron in the worm C. elegans, of type Layer 1 interneuron. The name stands for Anterior Ventral Process E Left. AVEL is a Ventral cord interneuron, like AVD but outputs restricted to anterior cord. The cell lineage of AVEL is AB alpppaaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 250, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8e5fe5b4-bda7-4fb4-b8c8-551496d9e352": {"__data__": {"id_": "8e5fe5b4-bda7-4fb4-b8c8-551496d9e352", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d2350707-0596-4540-a08d-e15cfbd27a26", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "a42de5701facfd8e81de10f394766a806d11c9639a7333d8030f98cab42ac483", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AVER is a neuron in the worm C. elegans, of type Layer 1 interneuron. The name stands for Anterior Ventral Process E Right. AVER is a Ventral cord interneuron, like AVD but outputs restricted to anterior cord. The cell lineage of AVER is AB praaaaaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 251, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "75daedfe-e3ce-43d4-a482-2d0911747baa": {"__data__": {"id_": "75daedfe-e3ce-43d4-a482-2d0911747baa", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "12c6466f-1be1-48d8-ad82-93f2167b7abf", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "c34d48464616df33fa90b43d219cdacdd6b492f405a6fdaf69f7ac5e2df5cdbc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AVFL is a neuron in the worm C. elegans, of type Layer 3 interneuron. The name stands for Anterior Ventral Process F Left. AVFL is a Interneuron. The cell lineage of AVFL is P1.aaaa/ W.aaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 189, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "eb4a1be6-f33a-4df4-9d79-2ba1a36130d4": {"__data__": {"id_": "eb4a1be6-f33a-4df4-9d79-2ba1a36130d4", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b26bef5f-1935-423e-b4c0-c7d37e72d46c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "90f2a6a486437be356fabed4671c5f9022a7d3872e9c1579fc300f5b1d0f360c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AVFR is a neuron in the worm C. elegans, of type Layer 3 interneuron. The name stands for Anterior Ventral Process F Right. AVFR is a Interneuron. The cell lineage of AVFR is P1.aaaa/ W.aaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 190, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6e40becc-bdcf-4d5c-a53d-6b5403e1d847": {"__data__": {"id_": "6e40becc-bdcf-4d5c-a53d-6b5403e1d847", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "240d61c6-58fb-470a-80fa-200becb7524d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "1a272715b3965416f2392e66a43a09f8c84b6c40dddd13408a7a3665fe0d49ce", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AVG is a neuron in the worm C. elegans, of type Layer 3 interneuron. The name stands for Anterior Ventral Process G. AVG is a Ventral cord interneuron. The cell lineage of AVG is AB prpapppap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 192, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "722207a0-d90c-4583-a859-9fca68c38051": {"__data__": {"id_": "722207a0-d90c-4583-a859-9fca68c38051", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6299798a-f521-44fa-91ce-82fc315b72fa", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "dfe848d824faa4eb37a4bccac2e93b78af68ebbdd1f33ead150a8b425a1a1182", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AVHL is a neuron in the worm C. elegans, of type Layer 3 interneuron. The name stands for Anterior Ventral Process H Left. AVHL is a Neuron, mainly postsynaptic in ventral cord and presynaptic in the ring. The cell lineage of AVHL is AB alapaaaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 247, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b8c871f8-3c49-4501-97b2-11d1b65d0e7a": {"__data__": {"id_": "b8c871f8-3c49-4501-97b2-11d1b65d0e7a", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e82b36eb-1e9c-491c-8744-fa99f7ed6f85", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "09da032000193422297e0fab3bf1496c2295251915e076c641faae194483bb76", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AVHR is a neuron in the worm C. elegans, of type Layer 3 interneuron. The name stands for Anterior Ventral Process H Right. AVHR is a Neuron, mainly postsynaptic in ventral cord and presynaptic in the ring. The cell lineage of AVHR is AB alappapaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 248, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "695065c1-c769-4962-a128-f41eaaced956": {"__data__": {"id_": "695065c1-c769-4962-a128-f41eaaced956", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d2338d23-07f2-4a6b-99bc-d18df565956e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "c1e138eb5ff473217b47e6fb9752fc1281c1aaad42f247c0217132c2cce1a828", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AVJL is a neuron in the worm C. elegans, of type Layer 2 interneuron. The name stands for Anterior Ventral Process J Left. AVJL is a Neuron, synapses like AVHL/R. The cell lineage of AVJL is AB alapapppa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 204, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7574aa5c-d0a0-4a06-83cb-79e89c2ec7e9": {"__data__": {"id_": "7574aa5c-d0a0-4a06-83cb-79e89c2ec7e9", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "670f2f48-8449-406a-b18b-c2615a3fc675", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "b9d3ded23f2bedac7c529fb27393e4ef8a831a29533579cb24c2edd6fb4e041a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AVJR is a neuron in the worm C. elegans, of type Layer 2 interneuron. The name stands for Anterior Ventral Process J Right. AVJR is a Neuron, synapses like AVHL/R. The cell lineage of AVJR is AB alapppppa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 205, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3838afc9-ec8c-46e1-b2cf-f0ebf3276b20": {"__data__": {"id_": "3838afc9-ec8c-46e1-b2cf-f0ebf3276b20", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "eba3ee9a-906d-4fa9-a763-45a8b66fe019", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "a874ee0d0186da344074d151ee624f3c25d393e1b5ccfdaf94d441d80a97be8d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AVKL is a neuron in the worm C. elegans, of type Layer 2 interneuron. The name stands for Anterior Ventral Process K Left. AVKL is a Ring and ventral cord interneuron. The cell lineage of AVKL is AB plpapapap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 209, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d2c8ece2-c7a1-45fd-8d40-8831f21f96a6": {"__data__": {"id_": "d2c8ece2-c7a1-45fd-8d40-8831f21f96a6", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6df6df6f-7af8-42a5-9c95-cad78b9543f0", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "7434a5bd57d2dbac5f712694f5ca079ff72d8d6dfad6b2db6376db44f99abc61", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AVKR is a neuron in the worm C. elegans, of type Layer 2 interneuron. The name stands for Anterior Ventral Process K Right. AVKR is a Ring and ventral cord interneuron. The cell lineage of AVKR is AB prpapapap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 210, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "abbcea80-4edd-4c55-ad38-27a2b03e7c39": {"__data__": {"id_": "abbcea80-4edd-4c55-ad38-27a2b03e7c39", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "59df4d5e-446a-4733-aaee-d80f75b8fe6c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "766068196e06fdd337d3cc67a63f019b0e7b986a49c637fb4bb91a2f4365434b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AVL is a neuron in the worm C. elegans, of type Layer 2 interneuron. The name stands for Anterior Ventral Process L. AVL is a Ring and ventral cord interneuron and an excitatory GABAergic motor neuron for rectal muscles. Few synapses. The cell lineage of AVL is AB prpappaap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 275, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e2794e42-2b37-415a-9315-3173f3c0470e": {"__data__": {"id_": "e2794e42-2b37-415a-9315-3173f3c0470e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "454e4a03-addc-4d9b-8d96-30d98de7f15c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "4a9ce54fd7f3e3cd58ad1e5fa28f9578bfbc566c29550b98c386cad47b2a6065", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AVM is a neuron in the worm C. elegans, of type Mechanosensory. The name stands for Anterior Ventral Microtubule Neuron. AVM is a Anterior ventral microtubule cell, touch receptor. The cell lineage of AVM is QR.paa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 215, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a6939e52-02bd-4c9f-b0ce-14a1819c078b": {"__data__": {"id_": "a6939e52-02bd-4c9f-b0ce-14a1819c078b", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a7d808e3-f763-4124-8741-6bf5c112c9e1", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "9b0d4206afad30c050cb1db2b43f92d108ca9ac6be7a73c7b60e9d4e6e1c53f9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AWAL is a neuron in the worm C. elegans, of type Amphid. The name stands for Amphid Wing Neuron A Left. AWAL is a Amphid wing cells, neurons having ciliated sheet-like sensory endings closely associated with amphid sheath. The cell lineage of AWAL is AB plaapapaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 264, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c4ffe4a5-08f7-4a19-8005-df12cc8673cb": {"__data__": {"id_": "c4ffe4a5-08f7-4a19-8005-df12cc8673cb", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cf01820a-667e-45a9-b99c-d646958b5c9a", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "ceffb20dbc48a8d44a43488460fed7bb7aaef04dca21423388411ec57040517a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AWAR is a neuron in the worm C. elegans, of type Amphid. The name stands for Amphid Wing Neuron A Right. AWAR is a Amphid wing cells, neurons having ciliated sheet-like sensory endings closely associated with amphid sheath. The cell lineage of AWAR is AB praapapaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 265, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0ff3cee6-46bd-42f0-b039-4c93526dd6eb": {"__data__": {"id_": "0ff3cee6-46bd-42f0-b039-4c93526dd6eb", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "06b722b9-e334-44d7-b6df-4b873f4ef888", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "c7979a8b34f31891a9866e926957077bfe5d33a18aa8141247ce101e078c8aca", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AWBL is a neuron in the worm C. elegans, of type Amphid. The name stands for Amphid Wing Neuron B Left. AWBL is a Amphid wing cells, neurons having ciliated sheet-like sensory endings closely associated with amphid sheath. The cell lineage of AWBL is AB alpppppap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 264, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3971cdb2-4a98-42b4-9a27-849cf4e81864": {"__data__": {"id_": "3971cdb2-4a98-42b4-9a27-849cf4e81864", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9fabbd78-505c-4f2f-9633-e66af1e9017c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "536ffdf33d1e2778b77d1ccabfd2a314b4203dbd6a0e4bd00951e966e542d453", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AWBR is a neuron in the worm C. elegans, of type Amphid. The name stands for Amphid Wing Neuron B Right. AWBR is a Amphid wing cells, neurons having ciliated sheet-like sensory endings closely associated with amphid sheath. The cell lineage of AWBR is AB praaappap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 265, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "443f3ddf-6e2f-4022-8aa2-8620575f398b": {"__data__": {"id_": "443f3ddf-6e2f-4022-8aa2-8620575f398b", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "36514703-793c-49de-8173-64f957eadb92", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "1a56efb44c23a3d37799420d9dc1314cf4d759720bbe03b360b4803df54d08bf", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AWCL is a neuron in the worm C. elegans, of type Amphid. The name stands for Amphid Wing Neuron C Left. AWCL is a Amphid wing cells, neurons having ciliated sheet-like sensory endings closely associated with amphid sheath. The cell lineage of AWCL is AB plpaaaaap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 264, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "acfff3d6-3c55-4185-89b8-7831cc8a564f": {"__data__": {"id_": "acfff3d6-3c55-4185-89b8-7831cc8a564f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "614760ef-6920-4f48-86db-1d24ce8ea032", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "33b39d30bcb8833dcd7547ef17c0d3595ea206fc159a2b30fc79c311ac704f93", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "AWCR is a neuron in the worm C. elegans, of type Amphid. The name stands for Amphid Wing Neuron C Right. AWCR is a Amphid wing cells, neurons having ciliated sheet-like sensory endings closely associated with amphid sheath. The cell lineage of AWCR is AB prpaaaaap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 265, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "57cb0ace-154a-4a2f-9e3f-0800ed04ed13": {"__data__": {"id_": "57cb0ace-154a-4a2f-9e3f-0800ed04ed13", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b2411843-f919-4d54-92c8-d8889bef4438", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "b901fca78e8651fb1153f91690fa59194a31de8e8ed1b8094d59d21d9bcf14b6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "BAGL is a neuron in the worm C. elegans, of type O2, CO2, social signals, touch. The name stands for BAG-like Dendritic Ending Left. BAGL is a Neuron, ciliated ending in head, no supporting cells, associated with ILso. The cell lineage of BAGL is AB alppappap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 260, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "aeceac69-fb8b-40db-ac49-5edc0eccb5bb": {"__data__": {"id_": "aeceac69-fb8b-40db-ac49-5edc0eccb5bb", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a97c0bd2-29ff-4a28-bb9d-8752ff40ea85", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "7951b5c70244d7f5600aa0cea04126814f2bbf2109bbb11c7aeda08ae22cee30", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "BAGR is a neuron in the worm C. elegans, of type O2, CO2, social signals, touch. The name stands for BAG-like Dendritic Ending Right. BAGR is a Neuron, ciliated ending in head, no supporting cells, associated with ILso. The cell lineage of BAGR is AB arappppap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 261, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9c6b0e94-d57d-4c9e-bb7d-2a7846fc60c1": {"__data__": {"id_": "9c6b0e94-d57d-4c9e-bb7d-2a7846fc60c1", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "44a1079d-54f9-4eee-b94f-c993613698c4", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "12387a0dd96524a4867355eb2e89f9527e37091295402efca39d750fe5700df0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "BDUL is a neuron in the worm C. elegans, of type Layer 3 interneuron. The name stands for Black Vesicles, Deirid Locale, Unknown Function Left. BDUL is a Neuron, process runs along excretory canal and into ring, unique darkly staining synaptic vesicles. The cell lineage of BDUL is AB arppaappp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 295, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cee65dac-a53b-426f-b54f-b3b7c7093c37": {"__data__": {"id_": "cee65dac-a53b-426f-b54f-b3b7c7093c37", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d36d5d27-5a2a-4c30-9467-2bcdbcb00030", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "a517f98f0716dbe5c0e5f00c7f495e29d7dd74a96af3aa0bd45a0ee38bdde444", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "BDUR is a neuron in the worm C. elegans, of type Layer 3 interneuron. The name stands for Black Vesicles, Deirid Locale, Unknown Function Right. BDUR is a Neuron, process runs along excretory canal and into ring, unique darkly staining synaptic vesicles. The cell lineage of BDUR is AB arpppappp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 296, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9c197255-47f7-4051-8eea-bdd100c033e6": {"__data__": {"id_": "9c197255-47f7-4051-8eea-bdd100c033e6", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1532b182-d3d7-438f-a09e-ad80286153d9", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "174f8fbbe45fdc78e9fad7119ae80f7eedea32b2e7ae51153f3ec1d92555251f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "CANL is a neuron in the worm C. elegans, of type Canal neuron. The name stands for Excretory CANal-associated Neuron Left. CANL is a Process runs along excretory canal, no synapses, essential for survival. The cell lineage of CANL is AB alapaaapa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 247, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c8bceec1-e27c-4986-b29d-5d48e723c4b1": {"__data__": {"id_": "c8bceec1-e27c-4986-b29d-5d48e723c4b1", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ea556eb0-fbd4-443c-9e4a-82a8dd7235ab", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "8aedfb1fc6b35799ef5d0edcabee338f24532cc734c4bab5719aff25d208603e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "CANR is a neuron in the worm C. elegans, of type Canal neuron. The name stands for Excretory CANal-associated Neuron Right. CANR is a Process runs along excretory canal, no synapses, essential for survival. The cell lineage of CANR is AB alappappa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 248, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "160a8c77-75ae-4c7a-9a08-b3c2f23da2a5": {"__data__": {"id_": "160a8c77-75ae-4c7a-9a08-b3c2f23da2a5", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c74b7031-aa5c-4c04-9a23-f1a82bf05a3b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "99b5900f3deba50dfea33c403824402cbb9db943c6929f741a9e801d314261bf", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "CEPDL is a neuron in the worm C. elegans, of type Cephalic. The name stands for CEPhalic Sensory Neuron Dorsal Left. CEPDL is a Cephalic neurons, contain dopamine. The cell lineage of CEPDL is AB plaaaaappa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 207, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "310f83c7-41f0-49e0-bcae-c666ad413833": {"__data__": {"id_": "310f83c7-41f0-49e0-bcae-c666ad413833", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ae421dae-d63b-484a-932b-00c896d789aa", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "069634d078a1fc81de737cbe1469435913a704e4408f48bfed33e6e854861ee5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "CEPDR is a neuron in the worm C. elegans, of type Cephalic. The name stands for CEPhalic Sensory Neuron Dorsal Right. CEPDR is a Cephalic neurons, contain dopamine. The cell lineage of CEPDR is AB arpapaappa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 208, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9ff5a599-5f34-4476-994d-fcc091062b8c": {"__data__": {"id_": "9ff5a599-5f34-4476-994d-fcc091062b8c", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "aa4796b9-5afb-480f-82cb-1e8a61c34886", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "f5234cc4c3a7881202a70baf3fa1f9f95188115fa3228f61801a17d52a83d146", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "CEPVL is a neuron in the worm C. elegans, of type Cephalic. The name stands for CEPhalic Sensory Neuron Ventral Left. CEPVL is a Cephalic neurons, contain dopamine. The cell lineage of CEPVL is AB plpaappppa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 208, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b438fa7e-b73d-4e76-b31f-a31de8f4e8e6": {"__data__": {"id_": "b438fa7e-b73d-4e76-b31f-a31de8f4e8e6", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d83b82bf-8669-44d2-ae10-6538d238dc48", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "783be65aa3f3b21c5301b0269ec97a54fafb812e9f27aacfcfff65b4a1876751", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "CEPVR is a neuron in the worm C. elegans, of type Cephalic. The name stands for CEPhalic Sensory Neuron Ventral Right. CEPVR is a Cephalic neurons, contain dopamine. The cell lineage of CEPVR is AB prpaappppa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 209, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ea3101f2-ba73-4c90-b5c3-bb63f364e2a2": {"__data__": {"id_": "ea3101f2-ba73-4c90-b5c3-bb63f364e2a2", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "11ef509b-e704-4fe8-bdce-d3ecd3fa1946", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "d006192b516a77d91e949e3c4d0011ca86b6a63fdc38fbbc0ef7b31184608d0e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "DA1 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Dorsal A-type Motor Neuron 1. DA1 is a Ventral cord motor neurons, innervate dorsal muscles. The cell lineage of DA1 is AB prppapaap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 228, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "84f5f909-3c43-43ea-996e-e6bc313f62b9": {"__data__": {"id_": "84f5f909-3c43-43ea-996e-e6bc313f62b9", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9fbf532d-2f7a-44d0-a742-6f6b9fc62b92", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "79f42ba6110e62f6d6daf053bcb7d51533c29c956d6f5b8b70549b695f778622", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "DA2 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Dorsal A-type Motor Neuron 2. DA2 is a Ventral cord motor neurons, innervate dorsal muscles. The cell lineage of DA2 is AB plppapapa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 228, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ffde17e7-499d-473c-a94e-489713b85133": {"__data__": {"id_": "ffde17e7-499d-473c-a94e-489713b85133", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "70536e5d-694d-4319-a074-9e6d88cdaecd", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "1ecfdf03b0d9e609e6f9e44c50b3a030a314b5c377f5ed82515129fd89c78fb6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "DA3 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Dorsal A-type Motor Neuron 3. DA3 is a Ventral cord motor neurons, innervate dorsal muscles. The cell lineage of DA3 is AB prppapapa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 228, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ec781b72-aa4c-4e3b-be81-07bdebf1c9f1": {"__data__": {"id_": "ec781b72-aa4c-4e3b-be81-07bdebf1c9f1", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ed690edd-8c4a-46f0-9309-57758fef300e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "bab96bb974b021a79d61b536a554a1777851c7cfbccb03510aefcc8b1412aca2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "DA4 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Dorsal A-type Motor Neuron 4. DA4 is a Ventral cord motor neurons, innervate dorsal muscles. The cell lineage of DA4 is AB plppapapp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 228, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7286879d-9ec2-4e15-936c-d88c8548afd6": {"__data__": {"id_": "7286879d-9ec2-4e15-936c-d88c8548afd6", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e715bb23-0a73-4f44-a445-1a2342e9286e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "22bff10e38bfcfaf14569b0e203c15c1b1e54715034663babcce0880c099909b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "DA5 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Dorsal A-type Motor Neuron 5. DA5 is a Ventral cord motor neurons, innervate dorsal muscles. The cell lineage of DA5 is AB prppapapp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 228, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "67e385b1-601b-4154-8697-33899b421229": {"__data__": {"id_": "67e385b1-601b-4154-8697-33899b421229", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6dd6b917-7cd2-4c61-8b0c-b41039d5fc80", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "ee7ecbd95623e8278a47ae2335f013f16481faea9210b56ff545a88bb60853e7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "DA6 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Dorsal A-type Motor Neuron 6. DA6 is a Ventral cord motor neurons, innervate dorsal muscles. The cell lineage of DA6 is AB plpppaaap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 228, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0f707c5a-a4b8-4573-a72f-1b83173922cc": {"__data__": {"id_": "0f707c5a-a4b8-4573-a72f-1b83173922cc", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "334e8726-7a96-4937-8d5b-7d1487ae7f94", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "477342200c9a2a31345d5f9d576219638f4aa01e1d52a54cd93e843ff5cc63f0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "DA7 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Dorsal A-type Motor Neuron 7. DA7 is a Ventral cord motor neurons, innervate dorsal muscles. The cell lineage of DA7 is AB prpppaaap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 228, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "bca6c864-f017-4022-ac40-fdeff277a1f2": {"__data__": {"id_": "bca6c864-f017-4022-ac40-fdeff277a1f2", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8521ecfe-7bdc-473c-9c1f-518d7dd89c54", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "ce5dffa343fcf466bb0ab8a203d51ee3dde94e86913e31f63f3ebafe4f4da818", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "DA8 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Dorsal A-type Motor Neuron 8. DA8 is a Ventral cord motor neurons, innervate dorsal muscles. The cell lineage of DA8 is AB prpapappp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 228, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cd9ddf3c-759b-4ed9-a791-00829bfda150": {"__data__": {"id_": "cd9ddf3c-759b-4ed9-a791-00829bfda150", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "00e3079f-ee2f-4885-9ba4-dcb71c2b0436", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "a98949b4b1294be9692a3a884311bbd3a8e87fbe0cf3118c053b5896a5fe3ea7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "DA9 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Dorsal A-type Motor Neuron 9. DA9 is a Ventral cord motor neurons, innervate dorsal muscles. The cell lineage of DA9 is AB plpppaaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 228, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1f1c1e3c-f369-4249-9304-4e9812a59389": {"__data__": {"id_": "1f1c1e3c-f369-4249-9304-4e9812a59389", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "67d6309f-7d3a-4d2c-9f16-b84189917834", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "13a237a2b2685f8361a89260d41cc49fb4f22b0bb84137324db63df14202a9aa", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "DB1 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Dorsal B-type Motor Neuron 1. DB1 is a Ventral cord motor neurons, innervate dorsal muscles, reciprocal inhibitor (aka DB1/3). The cell lineage of DB1 is AB plpaaaapp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 262, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c882c910-ced3-4cb2-be02-96ee865f31d1": {"__data__": {"id_": "c882c910-ced3-4cb2-be02-96ee865f31d1", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0caade0c-6aad-478b-ae38-39a7014f2162", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "fde20241e62dbd4cfb40c95f5ef0b3e78431cab6fb8ec24696a1994ad410632b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "DB2 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Dorsal B-type Motor Neuron 2. DB2 is a Ventral cord motor neurons, innervate dorsal muscles, reciprocal inhibitor (aka DB3/1). The cell lineage of DB2 is AB arappappa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 262, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0f31b93c-153e-4d95-bd6e-533c3261b0a7": {"__data__": {"id_": "0f31b93c-153e-4d95-bd6e-533c3261b0a7", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "44df2560-f856-49c5-85b4-c50078530da1", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "a663a37b9a128ad833762f0ce6fb1928ab81e6c49b10e7efae89124d3923358f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "DB3 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Dorsal B-type Motor Neuron 3/1. DB3 is a Ventral cord motor neurons, innervate dorsal muscles, reciprocal inhibitor. The cell lineage of DB3 is AB prpaaaapp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 252, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ea0bdc15-d83a-4d42-8c28-ef299872cf29": {"__data__": {"id_": "ea0bdc15-d83a-4d42-8c28-ef299872cf29", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c7912642-637d-4a2c-b988-d6af098c984a", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "7ee407820c00c25de0e8faf07d00b988a813cd7746e56adeced2894b61b4471a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "DB4 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Dorsal B-type Motor Neuron 4. DB4 is a Ventral cord motor neurons, innervate dorsal muscles, reciprocal inhibitor. The cell lineage of DB4 is AB prpappapp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 250, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "83c7f158-a331-4c49-9b10-4d6749f1965a": {"__data__": {"id_": "83c7f158-a331-4c49-9b10-4d6749f1965a", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0900e51a-e4a0-46ba-8dd9-b6ac32bb2179", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "a7b080ddc4770a9647e398778a93276e409832a00b5429c7cd9722ad1e1300b0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "DB5 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Dorsal B-type Motor Neuron 5. DB5 is a Ventral cord motor neurons, innervate dorsal muscles, reciprocal inhibitor. The cell lineage of DB5 is AB plpapappp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 250, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "30f38ed4-9a84-4326-98d8-9881034bb72e": {"__data__": {"id_": "30f38ed4-9a84-4326-98d8-9881034bb72e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1c99f907-930e-4fbf-a9a5-b311f7ee75e0", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "b42d2120110cf1a77a208ffbd36dc5f6f3dca7c351a4f7adf00b75a46a0c647a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "DB6 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Dorsal B-type Motor Neuron 6. DB6 is a Ventral cord motor neurons, innervate dorsal muscles, reciprocal inhibitor. The cell lineage of DB6 is AB plppaappp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 250, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "096c0ba4-065e-40d7-b66a-3bd5d7fa9e7b": {"__data__": {"id_": "096c0ba4-065e-40d7-b66a-3bd5d7fa9e7b", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ca1312ec-ea6e-41cd-bf73-1b6a511db51a", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "372a27da4e2363dc65b29877961b7a1ae03dc606f18d758d7848d3dd80460f9b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "DB7 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Dorsal B-type Motor Neuron 7. DB7 is a Ventral cord motor neurons, innervate dorsal muscles, reciprocal inhibitor. The cell lineage of DB7 is AB prppaappp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 250, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "625a9a5e-3a30-45e0-bc37-435f2f10f10c": {"__data__": {"id_": "625a9a5e-3a30-45e0-bc37-435f2f10f10c", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ba431a8f-9918-4a3c-af98-830cff869bb2", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "300e81dc04dc663ccaaff79e6c47e5ff87b5b66ab6ac86416e8f4ea486400925", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "DD1 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Dorsal D-type Motor Neuron 1. DD1 is a Ventral cord motor neurons, reciprocal inhibitors, change synaptic pattern during L1. The cell lineage of DD1 is AB plppappap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 260, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d18e1639-c041-41b2-81df-89eba82f9ea7": {"__data__": {"id_": "d18e1639-c041-41b2-81df-89eba82f9ea7", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5eccb661-5196-4b07-a2a1-b1ca1ca9a1fd", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "d0545bb4a2dc5558cb90e4d792d0b14e60efb72ccf1c32d380ae83b1a9d58258", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "DD2 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Dorsal D-type Motor Neuron 2. DD2 is a Ventral cord motor neurons, reciprocal inhibitors, change synaptic pattern during L1. The cell lineage of DD2 is AB prppappap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 260, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e6251960-31ca-43c8-9783-6e8ff546c124": {"__data__": {"id_": "e6251960-31ca-43c8-9783-6e8ff546c124", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c9216726-5696-48e8-bcaa-3256d015fbd2", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "df8e8dd26f87a0b26d8ae1df145c2765c230bc522955577cd6382b6cc2d3a71b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "DD3 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Dorsal D-type Motor Neuron 3. DD3 is a Ventral cord motor neurons, reciprocal inhibitors, change synaptic pattern during L1. The cell lineage of DD3 is AB plppapppa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 260, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "044b49d3-5e7b-4b51-b120-446ad4d1363e": {"__data__": {"id_": "044b49d3-5e7b-4b51-b120-446ad4d1363e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0559903d-23a9-4ef8-8558-94ef5d1e92ae", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "6ad6f11181860a15c33263cf0e1b29275b85e5daa28cab0df7326f712be2b527", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "DD4 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Dorsal D-type Motor Neuron 4. DD4 is a Ventral cord motor neurons, reciprocal inhibitors, change synaptic pattern during L1. The cell lineage of DD4 is AB prppapppa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 260, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d12dc1c9-cc05-4905-94fa-f34b16d326c3": {"__data__": {"id_": "d12dc1c9-cc05-4905-94fa-f34b16d326c3", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "04386cd3-a74c-4591-bea2-917eaeba1869", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "6613ac83591f335e5af535adaa9deec7902d9e368cd8e09de4e754f210c2f21e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "DD5 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Dorsal D-type Motor Neuron 5. DD5 is a Ventral cord motor neurons, reciprocal inhibitors, change synaptic pattern during L1. The cell lineage of DD5 is AB plppapppp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 260, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0ff3ff63-7f53-4e0d-90d2-071dac366365": {"__data__": {"id_": "0ff3ff63-7f53-4e0d-90d2-071dac366365", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "28727e87-79ce-4adf-a45b-f2053700af55", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "c88deb381c267f57b822988a3e818be114bc2983df3438347516d75faad7114b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "DD6 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Dorsal D-type Motor Neuron 6. DD6 is a Ventral cord motor neurons, reciprocal inhibitors, change synaptic pattern during L1. The cell lineage of DD6 is AB prppapppp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 260, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ea55cff2-479d-4443-84f8-0666b5caecf0": {"__data__": {"id_": "ea55cff2-479d-4443-84f8-0666b5caecf0", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f4674e79-e52b-49ab-8220-556aa4eaad36", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "379c4af4f72934042a286ee3ee189bc0212aed0b64850f58a69012cf9fd0e37b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "DVA is a neuron in the worm C. elegans, of type Mechanosensory. The name stands for Dorsorectal Ganglion Ventral Process A. DVA is a Ring interneurons, cell bodies in dorsorectal ganglion. The cell lineage of DVA is AB prppppapp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 229, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "654ca78c-2bd2-40e0-a9af-6cfeb19229ec": {"__data__": {"id_": "654ca78c-2bd2-40e0-a9af-6cfeb19229ec", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "41b4d4c0-8b1f-4eae-8224-b45ea6b9a30b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "4f2d2a326473afd99cea8c2f9a1bb153bf70bb33fbdb47fc96d06902ea8292d8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "DVB is a neuron in the worm C. elegans, of type Layer 3 interneuron. The name stands for Dorsorectal Ganglion Ventral Process B. DVB is a An excitatory GABAergic motor neuron/interneuron located in dorso-rectal ganglion. Innervates rectal muscles. The cell lineage of DVB is K.p.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 279, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c7afedca-a075-4ed3-90ad-208f684bb39f": {"__data__": {"id_": "c7afedca-a075-4ed3-90ad-208f684bb39f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e9da8832-e2c0-4dae-b005-2f5c440dc6d0", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "670196a107cbe22c272811b1b7cd36c6597f882f05a8db8a4920a159264c1f7c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "DVC is a neuron in the worm C. elegans, of type Layer 2 interneuron. The name stands for Dorsorectal Ganglion Ventral Process C. DVC is a Ring interneurons, cell bodies in dorsorectal ganglion. The cell lineage of DVC is C aapaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 229, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "30b73e25-ee8f-437a-9593-22a85177238f": {"__data__": {"id_": "30b73e25-ee8f-437a-9593-22a85177238f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3b070af2-ec03-435c-b1b8-e737b58e8476", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "c47336bf044c3328d8dcb9b3280a60a15d6f76f38e1f98092087f6bdd9b549bd", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "FLPL is a neuron in the worm C. elegans, of type Mechanosensory. The name stands for FLaP-like Dendritic Ending Left. FLPL is a Neuron, ciliated ending in head, no supporting cells, associated with ILso. The cell lineage of FLPL is AB plapaaapad.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 246, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b7db967f-2f16-4612-a720-b17a04c341e0": {"__data__": {"id_": "b7db967f-2f16-4612-a720-b17a04c341e0", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1415ec2e-b631-43d3-843b-eafcd06fa1a5", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "86062d70157f323fa6f6c0b02252f102ce1c498f3777a1951fa6a962119cde9c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "FLPR is a neuron in the worm C. elegans, of type Mechanosensory. The name stands for FLaP-like Dendritic Ending Right. FLPR is a Neuron, ciliated ending in head, no supporting cells, associated with ILso. The cell lineage of FLPR is AB prapaaapad.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 247, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "73fd383e-3338-4487-bae9-2e3b3a0a45f1": {"__data__": {"id_": "73fd383e-3338-4487-bae9-2e3b3a0a45f1", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "aa5be5e8-69a2-4854-a4ca-68406297ea9d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "24ba67efb98cf5b87ba2273f730527c4cd43adb9098126278f8c9ab0fb22d479", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "HSNL is a neuron in the worm C. elegans, of type Hermaphrodite specific motor neuron. The name stands for Hermaphrodite-Specific Neuron Left. HSNL is a Hermaphrodite specific motor neurons (die in male embryo), innervate vulval muscles, serotonergic. The cell lineage of HSNL is AB plapppappa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 293, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "122e5c30-2eb2-4de2-b49c-fb3e2e73fdfc": {"__data__": {"id_": "122e5c30-2eb2-4de2-b49c-fb3e2e73fdfc", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "27aeef07-148a-4a74-b737-00cf605d9698", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "d46c97c05213d715559d5f655e951e98b02b689120faa4c30260c6350d0847d9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "HSNR is a neuron in the worm C. elegans, of type Hermaphrodite specific motor neuron. The name stands for Hermaphrodite-Specific Neuron Right. HSNR is a Hermaphrodite specific motor neurons (die in male embryo), innervate vulval muscles, serotonergic. The cell lineage of HSNR is AB prapppappa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 294, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d2546ec8-14c4-42bf-b6e7-4876d1b5a519": {"__data__": {"id_": "d2546ec8-14c4-42bf-b6e7-4876d1b5a519", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "71310cdc-406b-4781-946f-e6c65c429a79", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "46d99e30a088c62b36dde5402e012124ec313d0834ae596c6c52a144dcfc2da4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "I1L is a neuron in the worm C. elegans, of type Pharyngeal interneuron. The name stands for Interneuron 1 (pharynx) Left. I1L is a Pharyngeal interneurons: ant sensory, input from RIP. The cell lineage of I1L is AB alpapppaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 225, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d32b3a78-321f-44f7-8a8a-46ab5594cd90": {"__data__": {"id_": "d32b3a78-321f-44f7-8a8a-46ab5594cd90", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8c33862e-6c18-4138-979f-f5d2eae31a22", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "6b1531b5640b4c7c5cd05206c077a2b8fce60a15f937d75aa84b5bbc492eedcf", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "I1R is a neuron in the worm C. elegans, of type Pharyngeal interneuron. The name stands for Interneuron 1 (pharynx) Right. I1R is a Pharyngeal interneurons: ant sensory, input from RIP. The cell lineage of I1R is AB arapappaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 226, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a6f5afd9-f6bd-464a-8a6b-bfb0859858ac": {"__data__": {"id_": "a6f5afd9-f6bd-464a-8a6b-bfb0859858ac", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e07c0624-a2c3-40f8-861a-38e422ecbb86", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "6c70c6ae86ade215078b3e3d524830e3d592b6ed2d29fd0975ad84a94e5a02d4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "I2L is a neuron in the worm C. elegans, of type Pharyngeal interneuron. The name stands for Interneuron 2 (pharynx) Left. I2L is a Pharyngeal interneurons, ant sensory. The cell lineage of I2L is AB alpappaapa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 210, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "16643048-816e-4b28-b4f7-42a2378c1f04": {"__data__": {"id_": "16643048-816e-4b28-b4f7-42a2378c1f04", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "03d3db6d-0f28-40fc-85e8-728bda1e1b00", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "d7a134d0d47cc5ab9b743ecbda0983e97dc22b0789b05e90f37f7f8982127903", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "I2R is a neuron in the worm C. elegans, of type Pharyngeal interneuron. The name stands for Interneuron 2 (pharynx) Right. I2R is a Pharyngeal interneurons, ant sensory. The cell lineage of I2R is AB arapapaapa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 211, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4b4907bc-4f9f-444e-a1bb-ef07507fab24": {"__data__": {"id_": "4b4907bc-4f9f-444e-a1bb-ef07507fab24", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "920f7629-faf1-4218-9b5f-82264a17385a", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "229e0ae625af78ce9d551d15a32df1b38485d6bef9a184b2ce1e1f6b44356224", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "I3 is a neuron in the worm C. elegans, of type Pharyngeal interneuron. The name stands for Interneuron 3 (pharynx). I3 is a Pharyngeal interneuron, ant sensory. The cell lineage of I3 is MS aaaaapaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 199, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f3b64a50-7d29-4960-a599-f3b85189cf8e": {"__data__": {"id_": "f3b64a50-7d29-4960-a599-f3b85189cf8e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "08e5082a-c1f0-4718-a87b-18032d61c29c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "32c414820d8eb306b5bac8315d8d70fd92cb1f767e962e8f218f19c124ff8a26", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "I4 is a neuron in the worm C. elegans, of type Pharyngeal interneuron. The name stands for Interneuron 4 (pharynx). I4 is a Pharyngeal interneuron. The cell lineage of I4 is MS aaaapaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 185, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "38ae6373-d413-4160-bc5f-99c1c6e98f0c": {"__data__": {"id_": "38ae6373-d413-4160-bc5f-99c1c6e98f0c", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0596c9fb-c1ca-4e4c-9887-9a325038d380", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "e4ba925e8aea34c60490162c73298caa102397c00c54c763799543d020352eeb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "I5 is a neuron in the worm C. elegans, of type Pharyngeal interneuron. The name stands for Interneuron 5 (pharynx). I5 is a Pharyngeal interneuron, post sensory. The cell lineage of I5 is AB arapapapp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 201, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d66a19d0-7ef9-4115-afd8-8f20cd3a0102": {"__data__": {"id_": "d66a19d0-7ef9-4115-afd8-8f20cd3a0102", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0a4027a1-7000-4113-b209-23d295afe6f5", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "29f86fc3970d5839b7f5a08c1b9d69cbfacdb428ea2930e07d007528f64c72af", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "I6 is a neuron in the worm C. elegans, of type Pharyngeal interneuron. The name stands for Interneuron 6 (pharynx). I6 is a Pharyngeal interneuron, post sensory. The cell lineage of I6 is MS paaapaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 199, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4ce55c4f-6a4a-4997-85e2-55924ee32506": {"__data__": {"id_": "4ce55c4f-6a4a-4997-85e2-55924ee32506", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "73b3e241-18f9-49db-bb8a-690898bd6cfe", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "05b00ca2c642aa2305cf867ce53be64afeb385ff07fddbaeb2e3f70d32d21c05", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "IL1DL is a neuron in the worm C. elegans, of type Cephalic. The name stands for Inner Labial 1 Dorsal Left. IL1DL is a Inner labial neuron. The cell lineage of IL1DL is AB alapappaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 183, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0cb141ee-24f2-47b3-bcfd-4e73c4f4f7eb": {"__data__": {"id_": "0cb141ee-24f2-47b3-bcfd-4e73c4f4f7eb", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bd446263-bb5a-432c-b94e-29975657426e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "8deb121177863e964c7eb8acdb85ee39fde5da53093c803124184aa645b7e8a7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "IL1DR is a neuron in the worm C. elegans, of type Cephalic. The name stands for Inner Labial 1 Dorsal Right. IL1DR is a Inner labial neuron. The cell lineage of IL1DR is AB alappppaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 184, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "85dd685e-d27b-4439-959f-b540da2e3052": {"__data__": {"id_": "85dd685e-d27b-4439-959f-b540da2e3052", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d7075521-48ff-4bd3-ac53-64dc7e9e54fe", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "5360b1b37822bb06899c24719cbcd048d27e9f386434ff82f7a2aa3392ff73c8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "IL1L is a neuron in the worm C. elegans, of type Cephalic. The name stands for Inner Labial 1 Left. IL1L is a Inner labial neuron. The cell lineage of IL1L is AB alapaappaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 173, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b30141ab-76e3-4548-bd87-43a9cfcdda7e": {"__data__": {"id_": "b30141ab-76e3-4548-bd87-43a9cfcdda7e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "94ceb17e-3401-4752-8242-693fe253e1be", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "45c2768557b96c377187b836be7aa265329ef85b6fd7079e6c449a0c79de5bcc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "IL1R is a neuron in the worm C. elegans, of type Cephalic. The name stands for Inner Labial 1 Right. IL1R is a Inner labial neuron. The cell lineage of IL1R is AB alaappppaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 174, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "99944b00-f2a0-4c5d-a10c-bec6e423d274": {"__data__": {"id_": "99944b00-f2a0-4c5d-a10c-bec6e423d274", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "49b65acf-afd2-4ec9-acaa-310351d069d5", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "bb18aba984cf9242a9273937e241bcf888031333f3bcaab5754b65c093aa1a54", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "IL1VL is a neuron in the worm C. elegans, of type Cephalic. The name stands for Inner Labial 1 Ventral Left. IL1VL is a Inner labial neuron. The cell lineage of IL1VL is AB alppapppaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 184, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "96ac0f0b-94b4-40ee-bd29-228645e1e728": {"__data__": {"id_": "96ac0f0b-94b4-40ee-bd29-228645e1e728", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b73b12c2-5347-41bf-b893-5e3721f1c1ee", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "063b806057878dfc6661cdfd7141e79f68aef0558c9969de5bacd2eadc3857d9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "IL1VR is a neuron in the worm C. elegans, of type Cephalic. The name stands for Inner Labial 1 Ventral Right. IL1VR is a Inner labial neuron. The cell lineage of IL1VR is AB arapppppaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 185, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ab656b68-38bf-4779-8dfa-9d15c75a6bfa": {"__data__": {"id_": "ab656b68-38bf-4779-8dfa-9d15c75a6bfa", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "18800cf2-e535-4eaf-9b71-c20f40283fd5", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "645a3a6fcba25fbcaec425bc742dbab37cde6a390d0cf0883c296b006a6a6980", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "IL2DL is a neuron in the worm C. elegans, of type Cephalic. The name stands for Inner Labial 2 Dorsal Left. IL2DL is a Inner labial neuron. The cell lineage of IL2DL is AB alapappap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 182, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "911fa532-9be0-43b5-bf00-290d5df06db7": {"__data__": {"id_": "911fa532-9be0-43b5-bf00-290d5df06db7", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d92d6583-28ca-4f80-b6ad-5085d01b0e91", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "9f8df12f91531374fb465d56264d64539b20dce5b148e9fef2f35f3f6f80f22f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "IL2DR is a neuron in the worm C. elegans, of type Cephalic. The name stands for Inner Labial 2 Dorsal Right. IL2DR is a Inner labial neuron. The cell lineage of IL2DR is AB alappppap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 183, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "14784cef-56aa-4bcf-9029-6e2763b63551": {"__data__": {"id_": "14784cef-56aa-4bcf-9029-6e2763b63551", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2d5bafd6-a5d5-4dd6-89e4-f092155e2053", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "ce40fb9234f8b6381244ecab9ae1f83027b1f579bf60bb84ea954c21fa08ea39", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "IL2L is a neuron in the worm C. elegans, of type Cephalic. The name stands for Inner Labial 2 Left. IL2L is a Inner labial neuron. The cell lineage of IL2L is AB alapaappp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 172, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d55f2c11-c726-4efb-9109-95405e409635": {"__data__": {"id_": "d55f2c11-c726-4efb-9109-95405e409635", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "863bfb79-4eed-4388-a358-5b088628e9f2", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "65d8449e59380a518d5cb2927ace81ec764af0847b3ff9cbb15420a8f54a2d23", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "IL2R is a neuron in the worm C. elegans, of type Cephalic. The name stands for Inner Labial 2 Right. IL2R is a Inner labial neuron. The cell lineage of IL2R is AB alaappppp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 173, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "19d924f4-b78b-4316-850c-a45aa025c44a": {"__data__": {"id_": "19d924f4-b78b-4316-850c-a45aa025c44a", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0106f8b8-3aed-466b-8003-aa5f6195f70e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "fa2ff9a18f2a255b5acd6666265b6c86e1ff2f9c7f9109bc6068082e37a0a0d4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "IL2VL is a neuron in the worm C. elegans, of type Cephalic. The name stands for Inner Labial 2 Ventral Left. IL2VL is a Inner labial neuron. The cell lineage of IL2VL is AB alppapppp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 183, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "03884495-f7c5-490d-bac4-c02a3dd8d61e": {"__data__": {"id_": "03884495-f7c5-490d-bac4-c02a3dd8d61e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cdbaa0ca-5ef0-443a-bd83-4688d6892186", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "66219d0e051e8bdbc0d3abd7f6d53b177493dbbd63406734b438625b33d984ec", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "IL2VR is a neuron in the worm C. elegans, of type Cephalic. The name stands for Inner Labial 2 Ventral Right. IL2VR is a Inner labial neuron. The cell lineage of IL2VR is AB arapppppp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 184, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5f8f1909-b0ae-490c-bc1b-9865ad8c826c": {"__data__": {"id_": "5f8f1909-b0ae-490c-bc1b-9865ad8c826c", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "48a3cb97-f609-4a38-8599-422fa98c983f", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "2aca8c62286b8cb1c3047d6efeaecaba5ec5ecdcde6d84d6b8888d6e4981af75", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "LUAL is a neuron in the worm C. elegans, of type Layer 3 interneuron. The name stands for LUmbar Ganglion A Left. LUAL is a Interneuron, short process in post ventral cord. The cell lineage of LUAL is AB plpppaapap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 215, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "55c7ec6d-5186-4298-be28-77180392b6bc": {"__data__": {"id_": "55c7ec6d-5186-4298-be28-77180392b6bc", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "acebadec-e759-427e-9ba2-0ff636010755", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "b040abac2fa2714497e73047600c4b2c84c540c9259e069211fcb8d2f25b58e6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "LUAR is a neuron in the worm C. elegans, of type Layer 3 interneuron. The name stands for LUmbar Ganglion A Right. LUAR is a Interneuron, short process in post ventral cord. The cell lineage of LUAR is AB prpppaapap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 216, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c99a5620-16b0-4655-b2b5-516cbd4ffd8e": {"__data__": {"id_": "c99a5620-16b0-4655-b2b5-516cbd4ffd8e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "14f622ce-d1a1-43a5-bb7a-2af5f0005cd9", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "a121d6d45f7333b420bc109010500bf44aef090cb819407cbda9bbdd9ed8111a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "M1 is a neuron in the worm C. elegans, of type Pharyngeal motor neuron. The name stands for Motor Neuron 1 (pharynx). M1 is a Pharyngeal motorneuron. The cell lineage of M1 is MS paapaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 187, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "866cf9a7-0fb6-41ec-a453-88d5f8d81e2f": {"__data__": {"id_": "866cf9a7-0fb6-41ec-a453-88d5f8d81e2f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e7fc065f-b30a-4c47-93b9-8a5ed1f109dc", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "8478c37787eceae2fb468bcf8abd0aa5d150eec2a1d33c695d6cef3e86fe33d6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "M2L is a neuron in the worm C. elegans, of type Pharyngeal motor neuron. The name stands for Motor Neuron 2 (pharynx) Left. M2L is a Pharyngeal motorneurons. The cell lineage of M2L is AB araapappa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 198, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "728d862d-08d4-4466-8916-f5fa29b87d29": {"__data__": {"id_": "728d862d-08d4-4466-8916-f5fa29b87d29", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b331dac8-2062-41f5-82ae-187f02ce8d05", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "222f27231f55a9021b978c467238c26d5fe28663c1f4cc23d5a63c26c43c2cfa", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "M2R is a neuron in the worm C. elegans, of type Pharyngeal motor neuron. The name stands for Motor Neuron 2 (pharynx) Right. M2R is a Pharyngeal motorneurons. The cell lineage of M2R is AB araappppa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 199, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ed595aab-9cbf-4673-b8f8-31bbe7abdee0": {"__data__": {"id_": "ed595aab-9cbf-4673-b8f8-31bbe7abdee0", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "57cba1f5-9755-4620-8fa4-2fe999d890c8", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "9c29417b932bf744726cdd37bf61d9444d8e7c8c33386485bb8a93367403c235", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "M3L is a neuron in the worm C. elegans, of type Pharyngeal motor neuron. The name stands for Motor Neuron 3 (pharynx) Left. M3L is a Pharyngeal sensory-motorneurons. The cell lineage of M3L is AB araapappp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 206, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0a35b016-c91d-4610-adb5-4b3bbd871c4d": {"__data__": {"id_": "0a35b016-c91d-4610-adb5-4b3bbd871c4d", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "860eb76b-b11c-490d-8bd6-a3d1475cdf5b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "481ebd70d43ffce95aabf50ac9fb137b197eace403af53eb00be7db72afbad72", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "M3R is a neuron in the worm C. elegans, of type Pharyngeal motor neuron. The name stands for Motor Neuron 3 (pharynx) Right. M3R is a Pharyngeal sensory-motorneurons. The cell lineage of M3R is AB araappppp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 207, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "edadff22-d5e0-4c2e-bc8e-16769b7fbbbc": {"__data__": {"id_": "edadff22-d5e0-4c2e-bc8e-16769b7fbbbc", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ab2c25f9-c32e-4589-bb7e-91c8c30f6408", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "885beb7e337bf4cea51a397164689cee1d285f62f5df781e84087b7f67760709", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "M4 is a neuron in the worm C. elegans, of type Pharyngeal motor neuron. The name stands for Motor Neuron 4 (pharynx). M4 is a Pharyngeal motorneuron. The cell lineage of M4 is MS paaaaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 187, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a3c7915a-78ce-49a0-9bba-d954aa1a4526": {"__data__": {"id_": "a3c7915a-78ce-49a0-9bba-d954aa1a4526", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "accf87e9-0ddd-4e51-9690-ff4e4dbbc0aa", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "fe948ef0718510861456cbc5153720c41c90848e7fe723a5a4864245ffa23226", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "M5 is a neuron in the worm C. elegans, of type Pharyngeal motor neuron. The name stands for Motor Neuron 5 (pharynx). M5 is a Pharyngeal motorneuron. The cell lineage of M5 is MS paaapap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 187, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1d9d406c-acaf-4bbe-9863-ad001244e0ec": {"__data__": {"id_": "1d9d406c-acaf-4bbe-9863-ad001244e0ec", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cc4bd035-8890-4fa2-b6c1-3d3c6ad2d22f", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "d9defd20f00f2ded69c3d4e48b9927ca18fe50ac70d438a9937e5f9490ab2278", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "MCL is a neuron in the worm C. elegans, of type Pharyngeal polymodal neuron. The name stands for Marginal Cell Neuron (pharynx) Left. MCL is a Pharyngeal neurons that synapse onto marginal cells. The cell lineage of MCL is AB alpaaappp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 236, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f699003a-e429-4648-9c3b-76ec8896da90": {"__data__": {"id_": "f699003a-e429-4648-9c3b-76ec8896da90", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1947d58b-d74b-4994-8db9-78c9992aebc6", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "89aa90352f5731eb3f7fd411c6202715589f6f9d1338e4a00de66c0a10e51951", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "MCR is a neuron in the worm C. elegans, of type Pharyngeal polymodal neuron. The name stands for Marginal Cell Neuron (pharynx) Right. MCR is a Pharyngeal neurons that synapse onto marginal cells. The cell lineage of MCR is AB arapaappp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 237, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "07a21b87-1026-4eb4-8857-5412b1ba83fc": {"__data__": {"id_": "07a21b87-1026-4eb4-8857-5412b1ba83fc", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5453ba9e-9675-4f21-b39a-e6702e48acf8", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "adff74707e37af2bf4e894f5ec39d98ca038f425de14c4715ac5529b58eb3eb7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "MI is a neuron in the worm C. elegans, of type Pharyngeal polymodal neuron. The name stands for Motor/Interneuron (pharynx). MI is a Pharyngeal motor neuron/interneuron. The cell lineage of MI is AB araappaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 209, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d4e1394d-b2d7-4e88-96ab-20ca602f67c6": {"__data__": {"id_": "d4e1394d-b2d7-4e88-96ab-20ca602f67c6", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "38c63fb6-ed05-4932-bbda-6b85147c83bd", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "6da28ed4d32e789e377c16daef2e69ca07fd6082f2da2e32ed169cadbf3b4b7d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "NSML is a neuron in the worm C. elegans, of type Pharyngeal polymodal neuron. The name stands for NeuroSecretory Motor Neuron (pharynx) Left. NSML is a Pharyngeal neurosecretory motorneuron, contain serotonin. The cell lineage of NSML is AB araapapaav.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 252, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "11e0c69f-c672-4895-a6de-4ba6a05bf3b6": {"__data__": {"id_": "11e0c69f-c672-4895-a6de-4ba6a05bf3b6", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c227bc94-85ff-47f8-acf5-5b137d38dd29", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "21d439deb64e0106ca6603a9411154d0e6cd48dddfa50924a0c3bfad683c509b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "NSMR is a neuron in the worm C. elegans, of type Pharyngeal polymodal neuron. The name stands for NeuroSecretory Motor Neuron (pharynx) Right. NSMR is a Pharyngeal neurosecretory motorneuron, contain serotonin. The cell lineage of NSMR is AB araapppaav.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 253, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d5062f0d-e219-4052-a2fb-6eac6952465c": {"__data__": {"id_": "d5062f0d-e219-4052-a2fb-6eac6952465c", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "804aa735-3ff3-402f-9116-14a77bfb551f", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "76cb865aae8f6453cbf1bbc369be0f5584e23315ba2ef55e785797dfbf9d9ae4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "OLLL is a neuron in the worm C. elegans, of type Cephalic. The name stands for Outer Labial Lateral Dendrite Left. OLLL is a Lateral outer labial neurons. The cell lineage of OLLL is AB alppppapaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 197, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9b0bc2db-22f5-44f4-b7d3-9e7695f7b3e2": {"__data__": {"id_": "9b0bc2db-22f5-44f4-b7d3-9e7695f7b3e2", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e90d2b44-f4a7-4a66-adef-57ff0f3447c4", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "c579e5d5af8c3c4ad068d118883ce19a09294d989a74a4cae31e60a3df545905", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "OLLR is a neuron in the worm C. elegans, of type Cephalic. The name stands for Outer Labial Lateral Dendrite Right. OLLR is a Lateral outer labial neurons. The cell lineage of OLLR is AB praaapapaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 198, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8b88e0a6-52ab-4384-9400-87534d55b969": {"__data__": {"id_": "8b88e0a6-52ab-4384-9400-87534d55b969", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e3bec9dd-73e5-41ec-a520-391c9258bc94", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "d3162fab54a9d1ea1ca729d0b85436ed596af02c8a6a67175df0cd47ef015c44", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "OLQDL is a neuron in the worm C. elegans, of type Cephalic. The name stands for Outer Labial Quadrant Dendrite Dorsal Left. OLQDL is a Quadrant outer labial neuron. The cell lineage of OLQDL is AB alapapapaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 208, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b32d78c9-e31e-4cda-a6d2-7ac5351288b6": {"__data__": {"id_": "b32d78c9-e31e-4cda-a6d2-7ac5351288b6", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c62a5dc2-bedd-45c0-ba18-d041dc64b042", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "7ea40e04ff512bff470a12f431b171fe9e806ddb4f7d9b0fd19d827846164afd", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "OLQDR is a neuron in the worm C. elegans, of type Cephalic. The name stands for Outer Labial Quadrant Dendrite Dorsal Right. OLQDR is a Quadrant outer labial neuron. The cell lineage of OLQDR is AB alapppapaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 209, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "330110e1-7acf-4935-b249-012ec6ce8b71": {"__data__": {"id_": "330110e1-7acf-4935-b249-012ec6ce8b71", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "38cc3f59-5ac1-4b52-a0d1-31cb0bf2796a", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "afb951ba80899836f93cf6d7e682f11b5d26bbd84a266ede914d948448854f2c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "OLQVL is a neuron in the worm C. elegans, of type Cephalic. The name stands for Outer Labial Quadrant Dendrite Ventral Left. OLQVL is a Quadrant outer labial neuron. The cell lineage of OLQVL is AB plpaaappaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 209, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c41cd221-36f1-491e-91c4-6fa0b1e1c6ea": {"__data__": {"id_": "c41cd221-36f1-491e-91c4-6fa0b1e1c6ea", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7dff1693-0769-4862-8dc4-491e269e14e8", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "6a7a9b016eb57a90ea9a5d840eca555479a4b8b1a8e76447d531549c20d6762d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "OLQVR is a neuron in the worm C. elegans, of type Cephalic. The name stands for Outer Labial Quadrant Dendrite Ventral Right. OLQVR is a Quadrant outer labial neuron. The cell lineage of OLQVR is AB prpaaappaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 210, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "480fff62-7894-4f08-952c-acbc3a9f9208": {"__data__": {"id_": "480fff62-7894-4f08-952c-acbc3a9f9208", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "38ee42de-3244-4805-a1ac-8dd8c4cb5cf9", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "89624fe07fcdc27f017127afd254e7b7956cbd05036085a97b7335d2f5c37071", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PDA is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Preanal Cell Body Dorsal Axon A. PDA is a Motor neuron, process in dorsal cord, same as Y cell in hermaphrodite, Y.a in male. The cell lineage of PDA is AB prpppaaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 261, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f061670f-4532-4285-9083-ab0b1b78b326": {"__data__": {"id_": "f061670f-4532-4285-9083-ab0b1b78b326", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "75735d3a-e57f-45e6-8041-76792042c1b6", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "8ea942824cbca73a36c62ad8fdac1ce0c7784b8c24257efa75054cefa3cb5718", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PDB is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Preanal Cell Body Dorsal Axon B. PDB is a Motor neuron, process in dorsal cord, cell body in pre-anal ganglion. The cell lineage of PDB is P12.apa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 242, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "49bfa2ea-003a-4222-9794-c38ef3b76083": {"__data__": {"id_": "49bfa2ea-003a-4222-9794-c38ef3b76083", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bce2cf9e-7437-455e-aaa1-9f9bc8d6a4b9", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "d9b24a1a0c7bdf2508d8c355d1aa3e8132952574ab098e5cfaaacaca1058313d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PDEL is a neuron in the worm C. elegans, of type Mechanosensory. The name stands for Posterior DEirid Left. PDEL is a Neuron, dopaminergic of postderid sensillum. The cell lineage of PDEL is V5L.paaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 200, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0508e72a-10f8-4725-873f-24e1ff36a708": {"__data__": {"id_": "0508e72a-10f8-4725-873f-24e1ff36a708", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f92f5d3d-d71f-49fa-bff0-70ce407107e4", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "79e1dca6158769209dde11c91c4786b267b0b0729166def8af6c802b66650b92", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PDER is a neuron in the worm C. elegans, of type Mechanosensory. The name stands for Posterior DEirid Right. PDER is a Neuron, dopaminergic of postderid sensillum. The cell lineage of PDER is V5R.paaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 201, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4d55c15d-fbac-4e76-b9e6-a2990c76205e": {"__data__": {"id_": "4d55c15d-fbac-4e76-b9e6-a2990c76205e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "10c6ed39-e323-4833-a2c4-d34367303587", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "4c0b92b46c80d89e0b3f95e7bd84040dcb393096aace64bd1764ff14e2d7d0dd", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PHAL is a neuron in the worm C. elegans, of type Phasmid. The name stands for PHasmid Neuron A Left. PHAL is a Phasmid neurons, chemosensory. The cell lineage of PHAL is AB plpppaapp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 183, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cca24a0f-7ad4-403a-b878-d78505a500d4": {"__data__": {"id_": "cca24a0f-7ad4-403a-b878-d78505a500d4", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6c47278d-c260-442e-aed8-9758c7ea85b0", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "2ad47a7bedec87964189eae1b665cca27b0bc5313e47c18a2175a8702a8b8a0b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PHAR is a neuron in the worm C. elegans, of type Phasmid. The name stands for PHasmid Neuron A Right. PHAR is a Phasmid neurons, chemosensory. The cell lineage of PHAR is AB prpppaapp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 184, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "22145f67-eb25-472a-bac0-b38bc93f6669": {"__data__": {"id_": "22145f67-eb25-472a-bac0-b38bc93f6669", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ca4e578c-e6d8-4dfc-bba5-d8abe199b997", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "d96bc5f5d0e4031471c9baa1843028e614bcdb9bfe90b812fd4f0b56012be553", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PHBL is a neuron in the worm C. elegans, of type Phasmid. The name stands for PHasmid Neuron B Left. PHBL is a Phasmid neurons, chemosensory. The cell lineage of PHBL is AB plapppappp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 184, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c90cadfc-c735-4951-9bc5-9162d25ee53d": {"__data__": {"id_": "c90cadfc-c735-4951-9bc5-9162d25ee53d", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a68d6094-40b8-4935-85f9-fbec0dbb4220", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "ecbcb8bc15a5d93a2e7359f82472c5331734f7baec1c4dd615645e7960fd03a5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PHBR is a neuron in the worm C. elegans, of type Phasmid. The name stands for PHasmid Neuron B Right. PHBR is a Phasmid neurons, chemosensory. The cell lineage of PHBR is AB prapppappp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 185, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "faa293b7-0705-471d-a4e9-c16eabe4c6bc": {"__data__": {"id_": "faa293b7-0705-471d-a4e9-c16eabe4c6bc", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d30c0e5c-0d94-4ef9-9840-1075e0c8ede5", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "9533727e27a29ee890405722112784fd4969463b3ba033c5107a0c1023675c9a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PHCL is a neuron in the worm C. elegans, of type Phasmid. The name stands for PHasmid Neuron C Left. PHCL is a Neuron, striated rootlet in male, possibly sensory in tail spike. The cell lineage of PHCL is TL.pppaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 214, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f3f21350-de0d-4c3c-a8f3-93fd452ba2e8": {"__data__": {"id_": "f3f21350-de0d-4c3c-a8f3-93fd452ba2e8", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "915f0720-5c03-431e-acfd-5f75464d455e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "c14a53e2e1a8750a896b13ab6eaaba351e41d24c39af05e44af73b4b71b3ce7a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PHCR is a neuron in the worm C. elegans, of type Phasmid. The name stands for PHasmid Neuron C Right. PHCR is a Neuron, striated rootlet in male, possibly sensory in tail spike. The cell lineage of PHCR is TR.pppaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 215, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d7a4fcae-5ad5-415d-9b99-36fc4de950ad": {"__data__": {"id_": "d7a4fcae-5ad5-415d-9b99-36fc4de950ad", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9b10634d-1d08-4768-af5c-bb2ccda0167d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "4064c85a96b54c447acd21efb75d33daf5b4cc23c65da37c399a6fb434c1406f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PLML is a neuron in the worm C. elegans, of type Mechanosensory. The name stands for Posterior Lateral Microtubule Neuron Left. PLML is a Posterior lateral microtubule cells, touch receptor neurons. The cell lineage of PLML is AB plapappppaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 242, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "acfa9cba-7906-4bc0-b9a8-d0f6f7a90090": {"__data__": {"id_": "acfa9cba-7906-4bc0-b9a8-d0f6f7a90090", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b6a6efe3-6519-4e97-9985-3c616a19e985", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "fa3344b88f5a097b7f3721f82cc1eed7f07b77104a50093009153daff4548152", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PLMR is a neuron in the worm C. elegans, of type Mechanosensory. The name stands for Posterior Lateral Microtubule Neuron Right. PLMR is a Posterior lateral microtubule cells, touch receptor neurons. The cell lineage of PLMR is AB prapappppaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 243, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2ae0a897-05f3-426f-abcb-95f013a0b79e": {"__data__": {"id_": "2ae0a897-05f3-426f-abcb-95f013a0b79e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "36ac9ef3-3725-4db3-b28c-4adddd8c8b2b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "0e5d0e6227e7b982413e5644ee6ebe58698ec17ffe2d7e4864e19a678f5b2496", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PLNL is a neuron in the worm C. elegans, of type Touch. The name stands for Posterior Lateral N Left. PLNL is a Interneuron, associated with PLM. The cell lineage of PLNL is TL.pppap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 183, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c3800c02-22ad-4ce7-ab38-8d61bfcc11cd": {"__data__": {"id_": "c3800c02-22ad-4ce7-ab38-8d61bfcc11cd", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6eb9cfd6-e87b-4f01-b255-889f3b857773", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "10a08d8d5d4167d2edfbbc8bec9d7ec4048cc1ad12253613952bd64bfbc56fc4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PLNR is a neuron in the worm C. elegans, of type Touch. The name stands for Posterior Lateral N Right. PLNR is a Interneuron, associated with PLM. The cell lineage of PLNR is TR.pppap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 184, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "654b8a04-fe34-4a6a-9673-904ce73635c0": {"__data__": {"id_": "654b8a04-fe34-4a6a-9673-904ce73635c0", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2e7fb96a-5ede-426e-b38b-e71f033e9965", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "a3f06bd9b6aa6ae6a24d2c6a92db3ce005abe8640c99620b36719084c523461b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PQR is a neuron in the worm C. elegans, of type Touch. The name stands for Posterior Q-cell Derived Receptor. PQR is a Neuron, basal body, not part of a sensillum, projects into preanal ganglion. The cell lineage of PQR is QL.ap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 229, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "eadad077-f835-4a74-8c9b-a83690fe3a65": {"__data__": {"id_": "eadad077-f835-4a74-8c9b-a83690fe3a65", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b987e64c-a80f-492b-9662-8bf7e824ade1", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "21fea20018b7b1e01419747907e8b6b7f931d36a2ab948e042c428caea4ce075", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PVCL is a neuron in the worm C. elegans, of type Layer 1 interneuron. The name stands for Posterior Ventral Process C Left. PVCL is a Ventral cord interneuron, cell body in lumbar ganglion, synapses onto VB and DB motor neurons, formerly called delta. The cell lineage of PVCL is AB plpppaapaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 294, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3e3a7f4c-c2da-4db6-9e6d-04be511c70cb": {"__data__": {"id_": "3e3a7f4c-c2da-4db6-9e6d-04be511c70cb", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2a542152-f0da-4c6b-a42c-3d9ff26d637f", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "dd300edebe9431b3a401485f3db9d00226a5500213d6925e15a81e593d467053", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PVCR is a neuron in the worm C. elegans, of type Layer 1 interneuron. The name stands for Posterior Ventral Process C Right. PVCR is a Ventral cord interneuron, cell body in lumbar ganglion, synapses onto VB and DB motor neurons, formerly called delta. The cell lineage of PVCR is AB prpppaapaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 295, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "305f5f33-dcc9-4fcc-b4c2-d35ff9727f96": {"__data__": {"id_": "305f5f33-dcc9-4fcc-b4c2-d35ff9727f96", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c264a7fc-d588-4810-b254-70f48b85d703", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "14cb69a2280b2107317a31c9bcbcef48f3d5e8866c78fb4ba9b33da0856fb1b2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PVDL is a neuron in the worm C. elegans, of type Mechanosensory. The name stands for Posterior Ventral Process D Left. PVDL is a Neuron, lateral process adjacent to excretory canal. The cell lineage of PVDL is V5L.paapa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 220, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "21d878b6-f132-4538-b38c-a211b4bcc691": {"__data__": {"id_": "21d878b6-f132-4538-b38c-a211b4bcc691", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "74e68bee-b9e4-4a6b-bb34-336984da1f9f", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "d9ec1091b066be13bec80f199460aecde9cbbc3adfa4450580fef14325613a5e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PVDR is a neuron in the worm C. elegans, of type Mechanosensory. The name stands for Posterior Ventral Process D Right. PVDR is a Neuron, lateral process adjacent to excretory canal. The cell lineage of PVDR is V5R.paapa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 221, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "440a6a2d-775a-4e10-ac3c-7c6c29f38831": {"__data__": {"id_": "440a6a2d-775a-4e10-ac3c-7c6c29f38831", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1f99f7a0-4866-41e3-bd64-be649b9e8b28", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "aefe780755d7d3127c902b1e7b572efdb0170ba7d18b9fecf431606d85fa8134", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PVM is a neuron in the worm C. elegans, of type Mechanosensory. The name stands for Posterior Ventral Microtubule Neuron. PVM is a Posterior ventral microtubule cell, touch receptor. The cell lineage of PVM is QL.paa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 217, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "859361bd-dddb-4303-94e2-f70b90045873": {"__data__": {"id_": "859361bd-dddb-4303-94e2-f70b90045873", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b41afca4-5d60-4a57-b198-0d139119a2fc", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "da3cbca7d2a9218a6da2f7c0f7e492d1b99d0feaca9efde8ae121ab7e0ed944a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PVNL is a neuron in the worm C. elegans, of type Layer 3 interneuron. The name stands for Posterior Ventral Process N Left. PVNL is a Interneuron/motor neuron, post. vent. cord, few synapses. The cell lineage of PVNL is TL.appp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 228, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "47dc89db-5264-4527-a884-acbacfb3d34c": {"__data__": {"id_": "47dc89db-5264-4527-a884-acbacfb3d34c", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b082f769-aba6-4f34-9a6b-d3d597b60ca3", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "4dc8f3a414b4774e2ba1e45a554d1bac40bae1da8429127e5d8f3dc491c662fa", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PVNR is a neuron in the worm C. elegans, of type Layer 3 interneuron. The name stands for Posterior Ventral Process N Right. PVNR is a Interneuron/motor neuron, post. vent. cord, few synapses. The cell lineage of PVNR is TR.appp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 229, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "de684761-18dd-4e8b-85b6-6553f763450b": {"__data__": {"id_": "de684761-18dd-4e8b-85b6-6553f763450b", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a0e96c43-003e-49ac-97e6-c42977c5f9b8", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "9575f6037b823c481658f41a120c0bc621ae4873a7c247276e06edb13313a730", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PVPL is a neuron in the worm C. elegans, of type Layer 3 interneuron. The name stands for Posterior Ventral Process P Left. PVPL is a Interneuron, cell body in preanal ganglion, projects along ventral cord to nerve ring. The cell lineage of PVPL is AB plppppaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 262, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0ea7bf0f-a8b8-4103-9433-2e9a7eece893": {"__data__": {"id_": "0ea7bf0f-a8b8-4103-9433-2e9a7eece893", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2c3bef81-891e-4cb2-980e-80de3894722d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "366d6bd41bec51310193b5d892a1a69cda467c6f4ff7d049bc5c224d5c1052ef", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PVPR is a neuron in the worm C. elegans, of type Layer 3 interneuron. The name stands for Posterior Ventral Process P Right. PVPR is a Interneuron, cell body in preanal ganglion, projects along ventral cord to nerve ring. The cell lineage of PVPR is AB prppppaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 263, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "dfaf8de4-f8ea-4ace-be4a-ebcc4c58024e": {"__data__": {"id_": "dfaf8de4-f8ea-4ace-be4a-ebcc4c58024e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6fab0b4f-e10f-4989-b8c6-ed059b6da200", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "78861d7f6eb8e068fa6d90b590f74d42f787e76debd8f0d65db3e41af57ce23c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PVQL is a neuron in the worm C. elegans, of type Layer 3 interneuron. The name stands for Posterior Ventral Process Q Left. PVQL is a Interneuron, projects along ventral cord to ring. The cell lineage of PVQL is AB plapppaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 225, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "07208557-16e6-4c81-bced-f337df3a6cb7": {"__data__": {"id_": "07208557-16e6-4c81-bced-f337df3a6cb7", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4fe5cd84-263b-4091-aebf-e6cbd3a8ed2d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "5aeafb85812cc6132fbd41c011a7d89d4feb49463e8b45022d62f833e341873d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PVQR is a neuron in the worm C. elegans, of type Layer 3 interneuron. The name stands for Posterior Ventral Process Q Right. PVQR is a Interneuron, projects along ventral cord to ring. The cell lineage of PVQR is AB prapppaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 226, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "eab516d8-a803-4782-89e8-cc4d81ed6d3b": {"__data__": {"id_": "eab516d8-a803-4782-89e8-cc4d81ed6d3b", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2e0fc789-5dc1-4a25-b489-477b1a6b5b38", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "38c43c692aa751421cac5804ca56849cd3576511165d72353e76b9cf2f16aca7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PVR is a neuron in the worm C. elegans, of type Layer 3 interneuron. The name stands for Posterior Ventral Process R. PVR is a Interneuron, projects along ventral cord to ring. The cell lineage of PVR is C aappa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 212, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ac5ac077-accd-4ffd-8515-9d6ff6eea1ab": {"__data__": {"id_": "ac5ac077-accd-4ffd-8515-9d6ff6eea1ab", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3b3042b0-3e2d-41ef-a92e-1f711ccc2b39", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "ef19ba225e05dcf4fc9d728b68132d3d86bf47232d7461cf6636640ae911c33b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PVT is a neuron in the worm C. elegans, of type Layer 2 interneuron. The name stands for Posterior Ventral Process T. PVT is a Interneuron, projects along ventral cord to ring. The cell lineage of PVT is AB plpappppa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 217, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "174bd899-f15c-4e59-9c77-e66f61fa9599": {"__data__": {"id_": "174bd899-f15c-4e59-9c77-e66f61fa9599", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "35ef4ab7-7443-4c61-8de3-546c8337abff", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "b80d126fa2617ecc97840d60895c199ba095cb63ece2f6cb32e576ca8fc91341", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PVWL is a neuron in the worm C. elegans, of type Layer 2 interneuron. The name stands for Posterior Ventral Process W Left. PVWL is a Interneuron, posterior ventral cord, few synapses. The cell lineage of PVWL is TL.ppa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 220, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "762d2806-81a2-415a-bf9c-c7ff64cd947b": {"__data__": {"id_": "762d2806-81a2-415a-bf9c-c7ff64cd947b", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "383e081e-0c6c-487e-8054-2636a7aebbb6", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "99fee864be7bcb245599f08df3cb517645c5c72772a928e3bf189517d4bbc0b7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PVWR is a neuron in the worm C. elegans, of type Layer 2 interneuron. The name stands for Posterior Ventral Process W Right. PVWR is a Interneuron, posterior ventral cord, few synapses. The cell lineage of PVWR is TR.ppa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 221, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "699ece38-e07f-4999-968f-543b3bb8ba02": {"__data__": {"id_": "699ece38-e07f-4999-968f-543b3bb8ba02", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "21617229-e6c4-4eb5-aec4-ff621a3704a1", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "4f28e315f7a933a02b7d561038378f7b381da6d797056e9c2d178041e4732d3c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RIAL is a neuron in the worm C. elegans, of type Layer 1 interneuron. The name stands for Ring Interneuron A Left. RIAL is a Ring interneuron, many synapses. The cell lineage of RIAL is AB alapaapaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 199, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e11cbd68-4217-4389-a826-ca13fc52ed42": {"__data__": {"id_": "e11cbd68-4217-4389-a826-ca13fc52ed42", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "835669ea-f88a-4ba1-bb16-2d86ea740693", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "cd4cfc3b7adb40bfdb8d215270167d75636841f1ed0a8ca05432f3e2966eccef", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RIAR is a neuron in the worm C. elegans, of type Layer 1 interneuron. The name stands for Ring Interneuron A Right. RIAR is a Ring interneuron, many synapses. The cell lineage of RIAR is AB alaapppaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 200, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5926eda3-c1cb-48fb-bba6-99e89d1fd627": {"__data__": {"id_": "5926eda3-c1cb-48fb-bba6-99e89d1fd627", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3d31e412-24dd-42c4-aaa1-a9dec7fe6157", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "dfb585b2d4ba03dc52cf84bd0ba23fad08dbd4e186ba2a8c5d247a8f9cc4d7c9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RIBL is a neuron in the worm C. elegans, of type Layer 2 interneuron. The name stands for Ring Interneuron B Left. RIBL is a Ring interneuron. The cell lineage of RIBL is AB plpaappap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 184, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fb09f291-1e3b-4cfb-adf0-4179d4935ce7": {"__data__": {"id_": "fb09f291-1e3b-4cfb-adf0-4179d4935ce7", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e2de29e3-b869-4e6c-bc5a-97f9a49e1832", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "13aec0889e93260359e29e0b0e7409e3a60027dca88bbf22fa99dcb058f8ee42", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RIBR is a neuron in the worm C. elegans, of type Layer 2 interneuron. The name stands for Ring Interneuron B Right. RIBR is a Ring interneuron. The cell lineage of RIBR is AB prpaappap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 185, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0edb7b1d-7904-4874-ac99-38e3d6ffc549": {"__data__": {"id_": "0edb7b1d-7904-4874-ac99-38e3d6ffc549", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3739f76d-689e-4d43-9ecb-4d93910c0f4a", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "e6b7a5d6426f65b1984b90d39736467a498357a466d937cca65dd7f6dfd5dde0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RICL is a neuron in the worm C. elegans, of type Layer 2 interneuron. The name stands for Ring Interneuron C Left. RICL is a Ring interneuron. The cell lineage of RICL is AB plppaaaapp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 185, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "bae4f484-7582-405e-b934-e3562d2f95c1": {"__data__": {"id_": "bae4f484-7582-405e-b934-e3562d2f95c1", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "355e81de-21c6-483d-847c-30913d0a2225", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "27cb762961397f3e5f56071c0c1c4621919d1455ee791614000021d7b1399368", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RICR is a neuron in the worm C. elegans, of type Layer 2 interneuron. The name stands for Ring Interneuron C Right. RICR is a Ring interneuron. The cell lineage of RICR is AB prppaaaapp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 186, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "be69d464-228a-41d3-ab4b-f860860b49ff": {"__data__": {"id_": "be69d464-228a-41d3-ab4b-f860860b49ff", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9adbaadc-9000-49e8-9f58-63d24f69f272", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "eefd50745da0c0c071c950749143f7007c2facf76f42b93d4acd52758074fffa", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RID is a neuron in the worm C. elegans, of type Layer 1 interneuron. The name stands for Ring Interneuron D. RID is a Ring interneuron, projects along dorsal cord. The cell lineage of RID is AB alappaapa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 204, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "52094266-0b8d-4013-9061-ce47bec4e7d6": {"__data__": {"id_": "52094266-0b8d-4013-9061-ce47bec4e7d6", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b4a59499-89c1-470b-8bd5-26dfbadd7951", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "a2379a6d744d7fc261078b2dd653c71ea37d6093329b0e46fd26134e1bdb45e4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RIFL is a neuron in the worm C. elegans, of type Layer 3 interneuron. The name stands for Ring Interneuron F Left. RIFL is a Ring interneuron. The cell lineage of RIFL is AB plppapaaap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 185, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5003ffac-251c-4f50-b64a-4aaab2121f76": {"__data__": {"id_": "5003ffac-251c-4f50-b64a-4aaab2121f76", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ab5c8ffd-7323-4308-9d28-4bdb72056a6b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "a85b64a157619c92f5758a88e8613400c3b060935b6c0574e9772717e014a684", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RIFR is a neuron in the worm C. elegans, of type Layer 3 interneuron. The name stands for Ring Interneuron F Right. RIFR is a Ring interneuron. The cell lineage of RIFR is AB prppapaaap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 186, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "626cd7f6-dc95-46aa-b91c-9479a4d08bab": {"__data__": {"id_": "626cd7f6-dc95-46aa-b91c-9479a4d08bab", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "dc48ed5f-7eca-4044-a82c-0636f16c7edb", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "60774e45ba78d2efe56275ebb7ea32b7b6ac6762cbb30965fb11d91b33e4c84e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RIGL is a neuron in the worm C. elegans, of type Layer 2 interneuron. The name stands for Ring Interneuron G Left. RIGL is a Ring interneuron. The cell lineage of RIGL is AB plppappaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 184, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e879bd29-b801-4887-a55a-7584ed28e790": {"__data__": {"id_": "e879bd29-b801-4887-a55a-7584ed28e790", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "64df93c6-42f2-4417-b285-4344461019a7", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "5c65382cf8d14ace7f5b50338f63e80dde70274eff14bf98fd78389d9e1e627a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RIGR is a neuron in the worm C. elegans, of type Layer 2 interneuron. The name stands for Ring Interneuron G Right. RIGR is a Ring interneuron. The cell lineage of RIGR is AB prppappaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 185, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7958d4b8-01f2-4ca9-be5e-314363623d3b": {"__data__": {"id_": "7958d4b8-01f2-4ca9-be5e-314363623d3b", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "29e0213b-476d-410c-941f-70343a9370ff", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "e37719601922f9e2151989be6e92b949a9223e22737933e64e1554314d265498", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RIH is a neuron in the worm C. elegans, of type Category 4 interneuron. The name stands for Ring Interneuron H. RIH is a Ring interneuron. The cell lineage of RIH is AB prpappaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 179, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f98a1ab5-5dca-4966-9569-9cfdcb7185ec": {"__data__": {"id_": "f98a1ab5-5dca-4966-9569-9cfdcb7185ec", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1ed51c67-146a-471b-8cc2-a7b9700e9103", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "b09980e8d8c3466f8d3e5ba58454dc957489d9615d4b9876757b8c716bb264b5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RIML is a neuron in the worm C. elegans, of type Layer 1 interneuron; motorneuron in White et al., 1986. The name stands for Ring Interneuron M Left. RIML is a Ring motor neuron. The cell lineage of RIML is AB plppaapap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 220, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "88d1b885-4902-4ff8-bf5e-a733ff0a00b6": {"__data__": {"id_": "88d1b885-4902-4ff8-bf5e-a733ff0a00b6", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "09a40ff8-7322-4557-9181-5f9c031f845e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "c59b350daf77eda9d405ed7d7797ba86f29e9d75fd3f7879b9860fa1660d07f2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RIMR is a neuron in the worm C. elegans, of type Layer 1 interneuron; motorneuron in White et al., 1986. The name stands for Ring Interneuron M Right. RIMR is a Ring motor neuron. The cell lineage of RIMR is AB prppaapap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 221, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f774f6a0-5c46-490b-a5f8-19fa1ee0baca": {"__data__": {"id_": "f774f6a0-5c46-490b-a5f8-19fa1ee0baca", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5879ba78-54e2-41ab-8477-380d40df2dd2", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "a776abde5fe3176ae34f9004f037f48560959290b3d6433b363d8379afda1717", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RIPL is a neuron in the worm C. elegans, of type Linker to pharynx. The name stands for Ring Interneuron P Left. RIPL is a Ring/pharynx interneuron, only direct connection between pharynx and ring. The cell lineage of RIPL is AB alpapaaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 239, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c79f313b-e54c-4586-a955-5234751f96c0": {"__data__": {"id_": "c79f313b-e54c-4586-a955-5234751f96c0", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7c9dd1cb-6cc2-4521-97d1-516a1c513d8b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "a90d9cd226af783d9e6e3c177d0e161fed5ef987ec5dd71f757f61798dce4553", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RIPR is a neuron in the worm C. elegans, of type Linker to pharynx. The name stands for Ring Interneuron P Right. RIPR is a Ring/pharynx interneuron, only direct connection between pharynx and ring. The cell lineage of RIPR is AB arappaaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 240, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7a226ab0-be62-4ad1-a4a4-e013552b14fd": {"__data__": {"id_": "7a226ab0-be62-4ad1-a4a4-e013552b14fd", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "77f6a4cb-5b51-459f-bcc4-c5b52918a40e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "57013567b0462f7b899af2ea0e5a8a12b16e0fb8f8e1f9f89610127e8ddef421", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RIR is a neuron in the worm C. elegans, of type Category 4 interneuron. The name stands for Ring Interneuron R. RIR is a Ring interneuron. The cell lineage of RIR is AB prpapppaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 179, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b82227e5-1ff3-4dd7-b51c-76d24b329b65": {"__data__": {"id_": "b82227e5-1ff3-4dd7-b51c-76d24b329b65", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "18d9aa55-6812-4464-bd60-70642aa356cb", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "179e09a17ec4d5dd1d9da3a82a766c220a0dd0333ea2e63cc3df5cf3f4d62a4e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RIS is a neuron in the worm C. elegans, of type Layer 3 interneuron. The name stands for Ring Interneuron S. RIS is a Ring interneuron. The cell lineage of RIS is AB prpappapa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 176, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7b8122ff-461e-4166-800f-0329b65ebb36": {"__data__": {"id_": "7b8122ff-461e-4166-800f-0329b65ebb36", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9338744f-f065-4d7d-91ed-d00169237ddf", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "f57b8e911d49b4f4f60df33c0198220efd014750fbc40f949d98f83aa0dc0072", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RIVL is a neuron in the worm C. elegans, of type Head motor neuron. The name stands for Ring Interneuron V Left. RIVL is a Ring interneuron. The cell lineage of RIVL is AB plpaapaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 182, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "71cf9f9e-35a0-48f3-b7af-741bae8dfea2": {"__data__": {"id_": "71cf9f9e-35a0-48f3-b7af-741bae8dfea2", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "80196f1f-f4c8-4b69-8f65-cecb9fb46ad1", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "d1ac9038b60dc24e9fb0cf312c381b3065a93c8d5d4b7aa03f7e65d5ffcc6051", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RIVR is a neuron in the worm C. elegans, of type Head motor neuron. The name stands for Ring Interneuron V Right. RIVR is a Ring interneuron. The cell lineage of RIVR is AB prpaapaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 183, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "71493189-9078-4caa-a9c9-49c7935ebfb9": {"__data__": {"id_": "71493189-9078-4caa-a9c9-49c7935ebfb9", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "74204a16-c8b6-4047-8d2a-a5bf34bcd342", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "30a5a96efab4a452cc82b0dd5d3ae5f45255fce6075064bb7bc89229a30a936a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RMDDL is a neuron in the worm C. elegans, of type Head motor neuron. The name stands for Ring Motor Neuron D Dorsal Left. RMDDL is a Ring motor neuron/interneuron, many synapses. The cell lineage of RMDDL is AB alpapapaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 221, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c3e3671c-b221-4f03-bfd5-4b599e9397da": {"__data__": {"id_": "c3e3671c-b221-4f03-bfd5-4b599e9397da", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4722b282-8cdb-4805-b182-f9d80c70b574", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "ede12d96d154b92c829a2279c2aa9faa26b816689b68366077cbb9f942ce2f21", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RMDDR is a neuron in the worm C. elegans, of type Head motor neuron. The name stands for Ring Motor Neuron D Dorsal Right. RMDDR is a Ring motor neuron/interneuron, many synapses. The cell lineage of RMDDR is AB arappapaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 222, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9c8cb4d2-97df-4271-a619-9d1f94b2cc04": {"__data__": {"id_": "9c8cb4d2-97df-4271-a619-9d1f94b2cc04", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1e70778f-691b-45ec-98c8-04fff55ddd4d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "463e6c0989b4e42b31cebd232d7783f54c395a962ca82c67c8f273e76848c1df", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RMDL is a neuron in the worm C. elegans, of type Head motor neuron. The name stands for Ring Motor Neuron D Left. RMDL is a Ring motor neuron/interneuron, many synapses. The cell lineage of RMDL is AB alpppapad.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 211, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f2e98a2c-fb47-4cdf-bcb1-b4a57ff3c3a5": {"__data__": {"id_": "f2e98a2c-fb47-4cdf-bcb1-b4a57ff3c3a5", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "54a60896-f544-43bd-935d-9e89869907e5", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "6f0e2751b0e8820f15d4e3ab43127945f6a072a376d55c02ba0efb4bbcad3d46", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RMDR is a neuron in the worm C. elegans, of type Head motor neuron. The name stands for Ring Motor Neuron D Right. RMDR is a Ring motor neuron/interneuron, many synapses. The cell lineage of RMDR is AB praaaapad.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 212, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6c086521-5e2c-41e5-9b41-0cd73e8e60fc": {"__data__": {"id_": "6c086521-5e2c-41e5-9b41-0cd73e8e60fc", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e260edef-1112-4d1d-88b2-f85df77ee39f", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "f0f0365374aa9a8773c6b8434a98a2311e40e1e96860db7f030e55df6090eb7d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RMDVL is a neuron in the worm C. elegans, of type Head motor neuron. The name stands for Ring Motor Neuron D Ventral Left. RMDVL is a Ring motor neuron/interneuron, many synapses. The cell lineage of RMDVL is AB alppapaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 222, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d6fd6ddd-6b62-44b1-8974-98274ae793f0": {"__data__": {"id_": "d6fd6ddd-6b62-44b1-8974-98274ae793f0", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4b7b9110-f366-4fe6-87b5-8d2ab324f0e0", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "378cf9d8da8a0c447ac2c90e6ffe10cc7409a1ff1ced75229a54e5e45472f2c5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RMDVR is a neuron in the worm C. elegans, of type Head motor neuron. The name stands for Ring Motor Neuron D Ventral Right. RMDVR is a Ring motor neuron/interneuron, many synapses. The cell lineage of RMDVR is AB arapppaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 223, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "83ff3425-bec4-4ac0-800c-b27120479705": {"__data__": {"id_": "83ff3425-bec4-4ac0-800c-b27120479705", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d35917f0-3c49-4c60-8119-c3f75d985d57", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "dbc7bf0cfd187dd7e0f5fe5ec5cf7a5d2f8af9d85802af8147176ab24c152187", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RMED is a neuron in the worm C. elegans, of type Head motor neuron. The name stands for Ring Motor Neuron E Dorsal. RMED is a Ring motor neuron. The cell lineage of RMED is AB alapppaap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 186, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d3598f54-3edf-4b18-bd26-a63c1b0d72fb": {"__data__": {"id_": "d3598f54-3edf-4b18-bd26-a63c1b0d72fb", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "778ccf91-9840-44a4-8469-7ee300d5ad22", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "601bff1a7a21cfabcba18ec16950b30f334761f357d33ae835adf06e8a7cdd40", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RMEL is a neuron in the worm C. elegans, of type Head motor neuron. The name stands for Ring Motor Neuron E Left. RMEL is a Ring motor neuron. The cell lineage of RMEL is AB alaaaarlp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 184, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4d7a2a5a-2064-4af0-8a8b-b0719b4e3cd8": {"__data__": {"id_": "4d7a2a5a-2064-4af0-8a8b-b0719b4e3cd8", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "17dcfbe2-a735-45f6-9eb1-2e0f463159ee", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "e9529c2dd06b4e56037359c4a5036f5f3ddda6babcdb13c228698341e1fce7df", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RMER is a neuron in the worm C. elegans, of type Head motor neuron. The name stands for Ring Motor Neuron E Right. RMER is a Ring motor neuron. The cell lineage of RMER is AB alaaaarrp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 185, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "533ec63c-2c3d-4698-8503-89a4e00c963e": {"__data__": {"id_": "533ec63c-2c3d-4698-8503-89a4e00c963e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "73689fd9-0a6f-499c-bc3c-eb76d02323fa", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "37cdee5815c8e69d8d734940447b9b7cfdb329507b776ed7b80ba8f131fad896", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RMEV is a neuron in the worm C. elegans, of type Head motor neuron. The name stands for Ring Motor Neuron E Ventral. RMEV is a Ring motor neuron. The cell lineage of RMEV is AB plpappaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 187, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "24b68841-2a9d-4b68-8597-03efdc48b891": {"__data__": {"id_": "24b68841-2a9d-4b68-8597-03efdc48b891", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "80ad0ae9-c3ce-4422-99fe-1a62be8843b8", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "9d3031c3e191fdcc984b1184d0801df979a466424e66aa13d7d2e0ffe6f8e66d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RMFL is a neuron in the worm C. elegans, of type Layer 2 interneuron. The name stands for Ring Motor Neuron F Left. RMFL is a Ring motor neuron/interneuron. The cell lineage of RMFL is G2.al.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 191, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1aeb222c-bdec-41c5-9007-1b3a5671edf6": {"__data__": {"id_": "1aeb222c-bdec-41c5-9007-1b3a5671edf6", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "03d70f5b-f60c-4c77-9c68-edf676ed2f32", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "8d9604cd45c7c731cca96b76559bed7118b67f861f25876f80b325bdf5fee8e5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RMFR is a neuron in the worm C. elegans, of type Layer 2 interneuron. The name stands for Ring Motor Neuron F Right. RMFR is a Ring motor neuron/interneuron. The cell lineage of RMFR is G2.ar.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 192, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "dea14f6e-52ba-4f66-bf60-63c428c04bf9": {"__data__": {"id_": "dea14f6e-52ba-4f66-bf60-63c428c04bf9", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0a348af4-ba2b-4fc1-991a-cebf707eb95f", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "22d0cadb9d60b2bb4eb27d2eae1466ac5e8cf6e70d1f5e9f7776ac5d65aecce2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RMGL is a neuron in the worm C. elegans, of type Layer 2 interneuron. The name stands for Ring Motor Neuron G Left. RMGL is a Ring interneuron. The cell lineage of RMGL is AB plapaaapp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 185, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6ba69637-6d82-4769-b885-a1dd382f9d2b": {"__data__": {"id_": "6ba69637-6d82-4769-b885-a1dd382f9d2b", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fa54ec7c-9de5-496d-99a4-292b785215c2", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "ea004f51870b1f4a4790f658084f76d3215c73ff02292edeb4a6deb905d331ec", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RMGR is a neuron in the worm C. elegans, of type Layer 2 interneuron. The name stands for Ring Motor Neuron G Right. RMGR is a Ring interneuron. The cell lineage of RMGR is AB prapaaapp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 186, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "de4f4e7f-761a-4d65-8ef3-ed910dc2b6e1": {"__data__": {"id_": "de4f4e7f-761a-4d65-8ef3-ed910dc2b6e1", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "05ecc329-da5f-4c85-85b1-095296fdeb8e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "2c353fc8bf9e8ef847c8490c2812aa42a550a626776a175790f3d673e1fb4432", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RMHL is a neuron in the worm C. elegans, of type Head motor neuron. The name stands for Ring Motor Neuron H Left. RMHL is a Ring motor neuron/interneuron. The cell lineage of RMHL is G1.l.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 188, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "02a22214-c780-4043-90f3-b7e9758e133e": {"__data__": {"id_": "02a22214-c780-4043-90f3-b7e9758e133e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c16efe78-debe-46fe-be47-1ac53af3e44c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "40e98642eecbef6509f70e34e543fc673ae01cc855d4da92a48d4576b5224728", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RMHR is a neuron in the worm C. elegans, of type Head motor neuron. The name stands for Ring Motor Neuron H Right. RMHR is a Ring motor neuron/interneuron. The cell lineage of RMHR is G1.r.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 189, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e019d0fb-9a5d-43ba-a2b3-2f7ca5ec7859": {"__data__": {"id_": "e019d0fb-9a5d-43ba-a2b3-2f7ca5ec7859", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d7819d02-d40c-40b9-b2c4-2ba0d8c0befc", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "a4eeacf9688d4d5720361f8308eb19c56ea0f5cbe7841a1783b1176c5b308a98", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "SAADL is a neuron in the worm C. elegans, of type Layer 2 interneuron. The name stands for Sublateral Anterior A Dorsal Left. SAADL is a Ring interneuron, anteriorly projecting process that runs sublaterally. The cell lineage of SAADL is AB alppapapa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 251, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "efbef363-1b95-41c9-b715-60008286d836": {"__data__": {"id_": "efbef363-1b95-41c9-b715-60008286d836", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f2b9d7c0-ac8c-44ab-808a-3c932f9d85a6", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "a8d41185b96360dedc12aa9ca2f8ff5b4111d44f4a87a499cc7c7ea400f1423f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "SAADR is a neuron in the worm C. elegans, of type Layer 2 interneuron. The name stands for Sublateral Anterior A Dorsal Right. SAADR is a Ring interneuron, anteriorly projecting process that runs sublaterally. The cell lineage of SAADR is AB arapppapa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 252, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8704aa29-42a0-4de2-83ea-58343fa44aaf": {"__data__": {"id_": "8704aa29-42a0-4de2-83ea-58343fa44aaf", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "62abaf2b-39a9-4763-a381-18d109b7721f", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "58e57ed1eb646a2665b12e154f88c9cbddea12845a7c58556b857fccad41dbac", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "SAAVL is a neuron in the worm C. elegans, of type Layer 2 interneuron. The name stands for Sublateral Anterior A Ventral Left. SAAVL is a Ring interneuron, anteriorly projecting process that runs sublaterally. The cell lineage of SAAVL is AB plpaaaaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 252, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "63acf247-b829-4adc-9888-2ff5233bbea5": {"__data__": {"id_": "63acf247-b829-4adc-9888-2ff5233bbea5", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3301a301-ad05-498a-a005-063921b8b020", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "8d11ca5fda6286b4c9a9f19d7e52818b4ac47e2fe2c65895daf287e2c0e14214", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "SAAVR is a neuron in the worm C. elegans, of type Layer 2 interneuron. The name stands for Sublateral Anterior A Ventral Right. SAAVR is a Ring interneuron, anteriorly projecting process that runs sublaterally. The cell lineage of SAAVR is AB prpaaaaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 253, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c7a31809-e112-43eb-aeaa-a3fdc8de563e": {"__data__": {"id_": "c7a31809-e112-43eb-aeaa-a3fdc8de563e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6fc6b9f4-492f-4ba8-8a8a-d8600ffeb736", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "cc617ab27c8a3029fe9a2f65401fe52a8cb69e81ce591279ce0d4a3d3a49e046", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "SABD is a neuron in the worm C. elegans, of type Sublateral motor neuron; interneuron in White et al., 1986. The name stands for Sublateral Anterior B Dorsal. SABD is a Ring interneuron, anteriorly projecting process that runs sublaterally, synapses to anterior body muscles in L1. The cell lineage of SABD is AB plppapaap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 323, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "805fd866-1cff-4ddd-bd0c-c34e87aa20a9": {"__data__": {"id_": "805fd866-1cff-4ddd-bd0c-c34e87aa20a9", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fc2211b2-a364-4c69-9108-b88b1c6e1e5c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "8a71d06e9f632d6f71a0a43b97fbb37358dec9fe4ba0e043fc6e7a57fd79fe19", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "SABVL is a neuron in the worm C. elegans, of type Sublateral motor neuron; interneuron in White et al., 1986. The name stands for Sublateral Anterior B Ventral Left. SABVL is a Ring interneuron, anteriorly projecting process that runs sublaterally, synapses to anterior body muscles in L1. The cell lineage of SABVL is AB plppapaaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 333, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "231439d1-7194-4afc-be49-0dcb235f82bb": {"__data__": {"id_": "231439d1-7194-4afc-be49-0dcb235f82bb", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9cefeeab-f922-497e-95a1-0d7f31dad729", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "171089f6bd9edc78eb9482a5f022263b1b932caa04fd7d57cd6ff36daa195c63", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "SABVR is a neuron in the worm C. elegans, of type Sublateral motor neuron; interneuron in White et al., 1986. The name stands for Sublateral Anterior B Ventral Right. SABVR is a Ring interneuron, anteriorly projecting process that runs sublaterally, synapses to anterior body muscles in L1. The cell lineage of SABVR is AB prppapaaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 334, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e9a44c94-9493-4c2b-ae31-a7837aa35849": {"__data__": {"id_": "e9a44c94-9493-4c2b-ae31-a7837aa35849", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f8f401ca-ee18-4e74-9cde-a70538ab9e3f", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "d503b0532013441bd00df52631b71eb3e5640c5fdefe5b8f370b8aed5d40049d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "SDQL is a neuron in the worm C. elegans, of type Touch. The name stands for Sublateral Dorsal Q-cell Derived Left. SDQL is a Post. lateral interneuron, process projects into ring. The cell lineage of SDQL is QL.pap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 215, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fa0047ec-e803-4358-9428-82f16a927a8e": {"__data__": {"id_": "fa0047ec-e803-4358-9428-82f16a927a8e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "18fe2ebd-f2be-4f81-b6a6-2854b1445c77", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "d4ed9e734fa7e271d27584bdd44d53272f46a363b2dac5c976d644c86b0db63b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "SDQR is a neuron in the worm C. elegans, of type Touch. The name stands for Sublateral Dorsal Q-cell Derived Right. SDQR is a Ant. lateral interneuron, process projects into ring. The cell lineage of SDQR is QR.pap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 215, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c18fd6f9-3b2a-4cee-845c-cf6f39a8c191": {"__data__": {"id_": "c18fd6f9-3b2a-4cee-845c-cf6f39a8c191", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "627e8a80-1434-41ca-8884-94f0398089bf", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "fec4ab1c2a5d7a59c088f3b0f6b3fe5af07b0273c708e3d2331c93c2e8cbca16", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "SIADL is a neuron in the worm C. elegans, of type Sublateral motor neuron; interneuron in White et al., 1986. The name stands for Sublateral Interneuron A Dorsal Left. SIADL is a Receive a few synapses in the ring, have posteriorly directed processes that run sublaterally. The cell lineage of SIADL is AB plpapaapa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 316, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7854d59f-4eea-42ed-910a-37ac0f03f427": {"__data__": {"id_": "7854d59f-4eea-42ed-910a-37ac0f03f427", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1f3e429d-53fa-4559-80f2-01a1188503ed", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "24a374db0cf3578f6236ec123798cbfe253f4c202241b88c901c7ed349c51b24", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "SIADR is a neuron in the worm C. elegans, of type Sublateral motor neuron; interneuron in White et al., 1986. The name stands for Sublateral Interneuron A Dorsal Right. SIADR is a Receive a few synapses in the ring, have posteriorly directed processes that run sublaterally. The cell lineage of SIADR is AB prpapaapa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 317, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d8d52728-9d17-4309-b019-44e0f1fd2e2a": {"__data__": {"id_": "d8d52728-9d17-4309-b019-44e0f1fd2e2a", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cb2029e7-a52c-4412-907d-26a17567ca99", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "5756a48391f32863444ec58c6a03beb34dbca2994f07cec62f0fe5c73e713c80", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "SIAVL is a neuron in the worm C. elegans, of type Sublateral motor neuron; interneuron in White et al., 1986. The name stands for Sublateral Interneuron A Ventral Left. SIAVL is a Receive a few synapses in the ring, have posteriorly directed processes that run sublaterally. The cell lineage of SIAVL is AB plpapappa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 317, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a3328e08-4ec6-4c8f-b1c1-539923e07e18": {"__data__": {"id_": "a3328e08-4ec6-4c8f-b1c1-539923e07e18", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "562da3ea-044c-476b-bfba-bf9cdd077b27", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "1c343bae8af3c13a8b1d38c074807f12d08742c91042e9450904e56965cb4b0b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "SIAVR is a neuron in the worm C. elegans, of type Sublateral motor neuron; interneuron in White et al., 1986. The name stands for Sublateral Interneuron A Ventral Right. SIAVR is a Receive a few synapses in the ring, have posteriorly directed processes that run sublaterally. The cell lineage of SIAVR is AB prpapappa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 318, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f880948e-7246-408b-8081-9e204e7b79cc": {"__data__": {"id_": "f880948e-7246-408b-8081-9e204e7b79cc", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b9559e93-b01c-45d1-a412-e6b9777fc710", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "974b586a12f33c86ceda7da9ce5f63fe6ba5d877f76d56de5ed2b5f73a80dc66", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "SIBDL is a neuron in the worm C. elegans, of type Sublateral motor neuron; interneuron in White et al., 1986. The name stands for Sublateral Interneuron B Dorsal Left. SIBDL is a Similar to SIA. The cell lineage of SIBDL is AB plppaaaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 237, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "87b9fdd4-6469-4582-87bc-81a3b1597402": {"__data__": {"id_": "87b9fdd4-6469-4582-87bc-81a3b1597402", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "041d486a-48f2-47cb-a9ff-e7c79c8ee34f", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "74b6495f1f42b81b19fea609e58b52d5b66ecb22824289a6c05b1fe5d87f7ca6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "SIBDR is a neuron in the worm C. elegans, of type Sublateral motor neuron; interneuron in White et al., 1986. The name stands for Sublateral Interneuron B Dorsal Right. SIBDR is a Similar to SIA. The cell lineage of SIBDR is AB prppaaaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 238, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "bd9ced55-ce82-42fa-a709-fddde61f3398": {"__data__": {"id_": "bd9ced55-ce82-42fa-a709-fddde61f3398", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "42f6cef3-3e36-4341-9d04-9512bbf0af4b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "5650bdfef0e711eefdff01450de7a6cb7183384c515ae5848bc12cff613b7950", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "SIBVL is a neuron in the worm C. elegans, of type Sublateral motor neuron; interneuron in White et al., 1986. The name stands for Sublateral Interneuron B Ventral Left. SIBVL is a Similar to SIA. The cell lineage of SIBVL is AB plpapaapp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 238, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a9b3aacf-8ad4-4f55-b944-374f4193462f": {"__data__": {"id_": "a9b3aacf-8ad4-4f55-b944-374f4193462f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f0d06475-3f4e-4545-ac90-de470b86c09d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "ea7033e6dd2a50ba1aa132317b75a961721d66321844edb19d96c4b1b285644d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "SIBVR is a neuron in the worm C. elegans, of type Sublateral motor neuron; interneuron in White et al., 1986. The name stands for Sublateral Interneuron B Ventral Right. SIBVR is a Similar to SIA. The cell lineage of SIBVR is AB prpapaapp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 239, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b681a426-6485-46db-9a82-0d1c184fc6dc": {"__data__": {"id_": "b681a426-6485-46db-9a82-0d1c184fc6dc", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "252d5c36-dab0-4678-ba9f-2c3b2efebd53", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "5389c3cf226ff451f20206bf5d61cbbffcd7aabf159b7c2606fd412eedccc11e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "SMBDL is a neuron in the worm C. elegans, of type Sublateral motor neuron. The name stands for Sublateral Motor Neuron B Dorsal Left. SMBDL is a Ring motor neuron/interneuron, has a posteriorly directed process that runs sublaterally. The cell lineage of SMBDL is AB alpapapapp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 278, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b4037bda-34bc-4bdf-8d35-bf6a867044eb": {"__data__": {"id_": "b4037bda-34bc-4bdf-8d35-bf6a867044eb", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7d01f08f-cdd9-4c31-bf34-aa0ac107d663", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "a02120dbdd376ae6d1676202d553a18ca6a54be70067a12da5c5660684d234a1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "SMBDR is a neuron in the worm C. elegans, of type Sublateral motor neuron. The name stands for Sublateral Motor Neuron B Dorsal Right. SMBDR is a Ring motor neuron/interneuron, has a posteriorly directed process that runs sublaterally. The cell lineage of SMBDR is AB arappapapp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 279, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1f546860-4108-4cde-a989-6a8fc0b8222e": {"__data__": {"id_": "1f546860-4108-4cde-a989-6a8fc0b8222e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "41d776db-99d6-4c7a-83ac-e63aa59d4740", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "a8d1e13e9854f463136e8ec461676ad3d1a67929db7799b73e368daf83911b2f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "SMBVL is a neuron in the worm C. elegans, of type Sublateral motor neuron. The name stands for Sublateral Motor Neuron B Ventral Left. SMBVL is a Ring motor neuron/interneuron, has a posteriorly directed process that runs sublaterally. The cell lineage of SMBVL is AB alpapappp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 278, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "910923e1-3a3b-49a9-9937-9da294716c33": {"__data__": {"id_": "910923e1-3a3b-49a9-9937-9da294716c33", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "256584c7-aa94-4b3c-8dba-49a1ad936f67", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "db1a7c799d9c3951cb940dc4474875e9aee8796780024206933d82192302d81d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "SMBVR is a neuron in the worm C. elegans, of type Sublateral motor neuron. The name stands for Sublateral Motor Neuron B Ventral Right. SMBVR is a Ring motor neuron/interneuron, has a posteriorly directed process that runs sublaterally. The cell lineage of SMBVR is AB arappappp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 279, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "992196d0-6053-4e41-886a-11145901fbe3": {"__data__": {"id_": "992196d0-6053-4e41-886a-11145901fbe3", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ce1a9d3b-1c1f-40e5-b277-6e5caa2b6b07", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "dd5d6e859a59b8f3c9ce12352abc2a50a862976bc06a1bf032381759ef547428", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "SMDDL is a neuron in the worm C. elegans, of type Sublateral motor neuron. The name stands for Sublateral Motor Neuron D Dorsal Left. SMDDL is a Ring motor neuron/interneuron, has a posteriorly directed process that runs sublaterally. The cell lineage of SMDDL is AB plpapaaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 277, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ba84625f-1aec-4505-80b0-424348833e06": {"__data__": {"id_": "ba84625f-1aec-4505-80b0-424348833e06", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "defd7226-78bf-4c13-87e7-854f72666d32", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "6dbc8b290f8cbc703fc2e917874da46cc2930ac442c16b64b43e02a66376075d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "SMDDR is a neuron in the worm C. elegans, of type Sublateral motor neuron. The name stands for Sublateral Motor Neuron D Dorsal Right. SMDDR is a Ring motor neuron/interneuron, has a posteriorly directed process that runs sublaterally. The cell lineage of SMDDR is AB prpapaaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 278, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "088e5c86-4ca1-4de5-a7f9-3bab05714a2e": {"__data__": {"id_": "088e5c86-4ca1-4de5-a7f9-3bab05714a2e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d060837a-411c-47c2-8ce9-428f46cff036", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "367b29cf78500c17c79b8899335455a81694f4cc5a018fb081dde087986dbff4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "SMDVL is a neuron in the worm C. elegans, of type Sublateral motor neuron. The name stands for Sublateral Motor Neuron D Ventral Left. SMDVL is a Ring motor neuron/interneuron, has a posteriorly directed process that runs sublaterally. The cell lineage of SMDVL is AB alppappaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 278, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "22aad5a1-973f-4cfb-8b23-84d54a52e352": {"__data__": {"id_": "22aad5a1-973f-4cfb-8b23-84d54a52e352", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "153f5e7d-3979-42b9-9615-5d3210c7162d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "a8a448c05f816946a298b1fe077106fc9c6fd9d4dd65eebd71a1fbe944d4db3e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "SMDVR is a neuron in the worm C. elegans, of type Sublateral motor neuron. The name stands for Sublateral Motor Neuron D Ventral Right. SMDVR is a Ring motor neuron/interneuron, has a posteriorly directed process that runs sublaterally. The cell lineage of SMDVR is AB arappppaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 279, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "854941d6-c2d9-4eb7-bec3-a7026342ce73": {"__data__": {"id_": "854941d6-c2d9-4eb7-bec3-a7026342ce73", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "dbaabef1-edac-43d6-aacb-4fa09db4113a", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "83e75272e4e64273b86ff05c98f6a3bbc66d54effb252e3dd38c76cf478216a7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "URADL is a neuron in the worm C. elegans, of type Head motor neuron. The name stands for Unknown Receptor, not Ciliated A Dorsal Left. URADL is a Ring motor neuron. The cell lineage of URADL is AB plaaaaaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 207, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "55fb9ec3-7755-476c-b953-2a383a64c47e": {"__data__": {"id_": "55fb9ec3-7755-476c-b953-2a383a64c47e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ee474b2c-df94-4ef8-9acc-83168f36d316", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "e5fa94e0c5cca3f344deb49c9eaa75b74d91c9ed6b27a3fdd21ce3c680066096", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "URADR is a neuron in the worm C. elegans, of type Head motor neuron. The name stands for Unknown Receptor, not Ciliated A Dorsal Right. URADR is a Ring motor neuron. The cell lineage of URADR is AB arpapaaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 208, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4ab8a200-f5eb-429d-9543-c1f9f11b0acc": {"__data__": {"id_": "4ab8a200-f5eb-429d-9543-c1f9f11b0acc", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8155a073-0f36-4a52-b982-d22552414591", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "4659d6c2b7aa3cdd87309187849d50cf7f02c2fcf6e3789988a099f01afb612a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "URAVL is a neuron in the worm C. elegans, of type Head motor neuron. The name stands for Unknown Receptor, not Ciliated A Ventral Left. URAVL is a Ring motor neuron. The cell lineage of URAVL is AB plpaaapaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 208, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "917035c9-5f42-4a31-8458-88fd318d42ed": {"__data__": {"id_": "917035c9-5f42-4a31-8458-88fd318d42ed", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "42c83624-81a1-4cf1-9638-520488ddb0b5", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "47fc355430c2be02256027f8c99bba7a325bcb64ecb25ffcfd739ea49190a76e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "URAVR is a neuron in the worm C. elegans, of type Head motor neuron. The name stands for Unknown Receptor, not Ciliated A Ventral Right. URAVR is a Ring motor neuron. The cell lineage of URAVR is AB prpaaapaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 209, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fbe1e2e3-b68e-4410-b564-1b4b9c506c7e": {"__data__": {"id_": "fbe1e2e3-b68e-4410-b564-1b4b9c506c7e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f89b950c-277b-4d0b-bc0d-77f4800a853e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "2bfca127fa3a373995197d192418d21604cd56307fd5990e2e88d23816ec4765", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "URBL is a neuron in the worm C. elegans, of type Category 4 interneuron. The name stands for Unknown Receptor, not Ciliated B Left. URBL is a Neuron, presynaptic in ring, ending in head. The cell lineage of URBL is AB plaapaapa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 228, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f5875a01-5481-4766-bd63-20e66fde668e": {"__data__": {"id_": "f5875a01-5481-4766-bd63-20e66fde668e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "577d4cbb-d892-4b08-a36b-a59d88a1c25c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "ef0d0a63750e27bb23f5d05a6f73983bfde92e264b7cc71f757b8fee173df67e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "URBR is a neuron in the worm C. elegans, of type Category 4 interneuron. The name stands for Unknown Receptor, not Ciliated B Right. URBR is a Neuron, presynaptic in ring, ending in head. The cell lineage of URBR is AB praapaapa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 229, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6eee07e2-e52c-4985-b8ae-a97b698ded9a": {"__data__": {"id_": "6eee07e2-e52c-4985-b8ae-a97b698ded9a", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f894b6bb-9ce8-4f1b-9b6f-89bfc8345180", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "4445693afcf8b67926c1a2616191ae91758d600625b869b64b51e499a164e051", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "URXL is a neuron in the worm C. elegans, of type O2, CO2, social signals, touch. The name stands for Unknown Receptor, not Ciliated X Left. URXL is a Ring interneuron. The cell lineage of URXL is AB plaaaaappp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 210, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a38ee18e-d5fc-4d8f-8b9f-ec317e9f924a": {"__data__": {"id_": "a38ee18e-d5fc-4d8f-8b9f-ec317e9f924a", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "efb90d5c-2b41-49d5-a522-44233e76bfa2", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "81c02c06887a220d77cc335d546c9fc527f78bc60804a90a3cbe079aa7f6dd4b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "URXR is a neuron in the worm C. elegans, of type O2, CO2, social signals, touch. The name stands for Unknown Receptor, not Ciliated X Right. URXR is a Ring interneuron. The cell lineage of URXR is AB arpapaappp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 211, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "75afbdc3-835a-475e-87d1-533cecf436f7": {"__data__": {"id_": "75afbdc3-835a-475e-87d1-533cecf436f7", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7e91beef-abf7-4779-959c-1e58e0390f86", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "e07f3e28f2f5df74710d1709ca457cb6082027a59090720f26e140245020dd77", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "URYDL is a neuron in the worm C. elegans, of type Cephalic. The name stands for Unknown Receptor, not Ciliated Y Dorsal Left. URYDL is a Neuron, presynaptic in ring, ending in head. The cell lineage of URYDL is AB alapapapp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 224, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "dfbfaf30-cf02-49fc-95dc-50b4d14e94d8": {"__data__": {"id_": "dfbfaf30-cf02-49fc-95dc-50b4d14e94d8", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "733642b0-0c6d-4164-b25a-b9bb73676282", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "f5ae7693d5143cb302be10f68833b86b675bfd72d35939ad0b4f5e5a81e647c8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "URYDR is a neuron in the worm C. elegans, of type Cephalic. The name stands for Unknown Receptor, not Ciliated Y Dorsal Right. URYDR is a Neuron, presynaptic in ring, ending in head. The cell lineage of URYDR is AB alapppapp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 225, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d72ad6af-4177-4bc3-b74c-8bf1f7b7f936": {"__data__": {"id_": "d72ad6af-4177-4bc3-b74c-8bf1f7b7f936", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "560b90c4-0b40-4584-a146-857f648e55e4", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "4c6425c2f2ce9142950ce6b379722689b8acf8899242d9024506b4b24a937f47", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "URYVL is a neuron in the worm C. elegans, of type Cephalic. The name stands for Unknown Receptor, not Ciliated Y Ventral Left. URYVL is a Neuron, presynaptic in ring, ending in head. The cell lineage of URYVL is AB plpaaappp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 225, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "05e00cdd-1f3b-493a-aad5-d8933b1f9b49": {"__data__": {"id_": "05e00cdd-1f3b-493a-aad5-d8933b1f9b49", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "badfa21d-d239-4d62-86be-543210e9cfb6", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "8d1a1b01d0545e6c710d45ca7e3dfa82d238851a9629df69f74956c21eeecd08", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "URYVR is a neuron in the worm C. elegans, of type Cephalic. The name stands for Unknown Receptor, not Ciliated Y Ventral Right. URYVR is a Neuron, presynaptic in ring, ending in head. The cell lineage of URYVR is AB prpaaappp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 226, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "af982a09-e391-4d95-9e88-dc0c8898e29d": {"__data__": {"id_": "af982a09-e391-4d95-9e88-dc0c8898e29d", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0ad27bc6-9a44-4e37-a4c8-93ccf2978586", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "68dee62dc439197847d772a6fd21ecf3f5a568eaeb81e32ef1735d8f5a97c0f0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "VA1 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Ventral A-type Motor Neuron 1. VA1 is a Ventral cord motor neuron, innervates vent. body muscles. The cell lineage of VA1 is W.pa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 225, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "52b09bb2-d1a3-4bfa-a80c-6d359de121f9": {"__data__": {"id_": "52b09bb2-d1a3-4bfa-a80c-6d359de121f9", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c2a6cc00-96a0-4188-83c6-abddc7e384d0", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "afc9971546c80d63b2af4482661a6fe3bb7dc4f49bfdc330392f62badca01b51", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "VA10 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Ventral A-type Motor Neuron 10. VA10 is a Ventral cord motor neuron, innervates vent. body muscles. The cell lineage of VA10 is P10.aaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 233, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3fd72ef9-d120-4180-be14-143b935c253d": {"__data__": {"id_": "3fd72ef9-d120-4180-be14-143b935c253d", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0df2a05a-476c-4165-b64e-d01c048d767b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "0a859ccbb89abe6318c762b636605144136dddb32b92d58790f7e5c29faf3959", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "VA11 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Ventral A-type Motor Neuron 11. VA11 is a Ventral cord motor neuron, innervates vent. body muscles. The cell lineage of VA11 is P11.aaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 233, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9b16d2d3-788a-482f-87c0-cb97e3f7128a": {"__data__": {"id_": "9b16d2d3-788a-482f-87c0-cb97e3f7128a", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fe35256b-e5b6-4b16-88e3-7fe80a70391e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "4df20e9f650ea7a8fde5525ce1944ec1ae394fde0e7db3077841241fa417d369", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "VA12 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Ventral A-type Motor Neuron 12. VA12 is a Ventral cord motor neuron, innervates vent. body muscles, but also interneuron in preanal ganglion. The cell lineage of VA12 is P12.aaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 275, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0a48c829-9731-4642-ba08-04967f7499a1": {"__data__": {"id_": "0a48c829-9731-4642-ba08-04967f7499a1", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e1e3c657-7506-478a-a3fd-9ade1d7e02ac", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "76b494e977f72601a4a850d359cc6c4feb1c07bb5e3ddc8368242795850676e7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "VA2 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Ventral A-type Motor Neuron 2. VA2 is a Ventral cord motor neuron, innervates vent. body muscles. The cell lineage of VA2 is P2.aaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 228, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cc494cf4-0702-46fb-a7a4-770513d8811e": {"__data__": {"id_": "cc494cf4-0702-46fb-a7a4-770513d8811e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ea62afa0-0cc9-4380-a1fd-d30ec12cbb9a", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "ccb21f5dcc02b55f5aa6c235d75a392c811ea91b7de525097cefb2061766ce13", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "VA3 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Ventral A-type Motor Neuron 3. VA3 is a Ventral cord motor neuron, innervates vent. body muscles. The cell lineage of VA3 is P3.aaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 228, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "40a75e29-a227-4791-b38e-20a6eeeff25a": {"__data__": {"id_": "40a75e29-a227-4791-b38e-20a6eeeff25a", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a9a5e851-ae3d-4c50-8b41-1f0f5a8935c1", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "a8ca1ccd21ba7b1e0f538165e3d977d85caafc3cda6684abf62d81b4de96b227", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "VA4 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Ventral A-type Motor Neuron 4. VA4 is a Ventral cord motor neuron, innervates vent. body muscles. The cell lineage of VA4 is P4.aaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 228, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4416da9a-22f5-43bc-8685-48fb0c2062d8": {"__data__": {"id_": "4416da9a-22f5-43bc-8685-48fb0c2062d8", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "624bd351-2d81-46e4-bc9a-2f3868c03d76", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "7649e26675a50bb6578adc108f86359c482609540ed71776cde401e7ba9cb1c3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "VA5 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Ventral A-type Motor Neuron 5. VA5 is a Ventral cord motor neuron, innervates vent. body muscles. The cell lineage of VA5 is P5.aaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 228, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "33c07e7b-00d4-4941-aab9-a3abb7fb4f68": {"__data__": {"id_": "33c07e7b-00d4-4941-aab9-a3abb7fb4f68", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8e19e169-911b-4ffd-9650-f62c8fbe26f0", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "7c96a8fd27a91f022b05d7538784ef53bd4d1236a9db948736177b10d0e3414c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "VA6 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Ventral A-type Motor Neuron 6. VA6 is a Ventral cord motor neuron, innervates vent. body muscles. The cell lineage of VA6 is P6.aaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 228, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9b37c72b-12ad-4b31-b886-bf453db87656": {"__data__": {"id_": "9b37c72b-12ad-4b31-b886-bf453db87656", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e90543de-2eed-4aa2-ab6a-89bc1a1fe2df", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "d184efc62da36bcfef036e45797f97e1b8e0d5ebabb98128a7e29e393eb9c669", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "VA7 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Ventral A-type Motor Neuron 7. VA7 is a Ventral cord motor neuron, innervates vent. body muscles. The cell lineage of VA7 is P7.aaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 228, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a20afff2-297f-44ed-8a01-a4252191cd48": {"__data__": {"id_": "a20afff2-297f-44ed-8a01-a4252191cd48", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "15fb48ea-966a-4419-9d48-19c78cf88ff9", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "103d0c46a6062a92aa5bcd9e2310deaef3cc400bd81f472cd1d92829d897d8e3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "VA8 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Ventral A-type Motor Neuron 8. VA8 is a Ventral cord motor neuron, innervates vent. body muscles. The cell lineage of VA8 is P8.aaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 228, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f64bea3a-9d43-478c-a8e5-1f802f1fe024": {"__data__": {"id_": "f64bea3a-9d43-478c-a8e5-1f802f1fe024", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "23d83f4f-ab26-4b99-890b-c15a1fddadbe", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "c8aef6d015048ed203614f10d0f22ee819dca4bb909670d3dca13efd1c0278df", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "VA9 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Ventral A-type Motor Neuron 9. VA9 is a Ventral cord motor neuron, innervates vent. body muscles. The cell lineage of VA9 is P9.aaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 228, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d519ddd6-bbdd-453b-9095-a3c2b4fad8c7": {"__data__": {"id_": "d519ddd6-bbdd-453b-9095-a3c2b4fad8c7", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fc434669-edda-4c8e-9381-c1d117768add", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "bd3cbd84dc7abeb46c1f2234e18eb59062914ec2f8f6086ba997af495b90b4b5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "VB1 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Ventral B-type Motor Neuron 1. VB1 is a Ventral cord motor neuron, innervates vent. body muscles, also interneuron in ring. 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The name stands for Ventral C-type Motor Neuron 6. VC6 is a Hermaphrodite specific ventral cord motor neuron innervates vulval muscles and ventral body muscles. The cell lineage of VC6 is P8.aap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 280, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "bb301731-7df1-4c09-b248-f10dd9138aa2": {"__data__": {"id_": "bb301731-7df1-4c09-b248-f10dd9138aa2", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a601e497-ef6c-4ef5-99cd-44d08ab75ed2", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "495ad681425e130f4bbdcefc1182d2fd0d3c2f56f8d2191bf9603d50ca186106", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "VD1 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Ventral D-type Motor Neuron 1. VD1 is a Ventral cord motor neuron, innervates vent body muscles, reciprocal inhibitor. The cell lineage of VD1 is W.pp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 246, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "82ebfaeb-f028-43a5-9158-5bdd2908ac14": {"__data__": {"id_": "82ebfaeb-f028-43a5-9158-5bdd2908ac14", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bd734743-9fde-4e6f-9ae1-2d1b159c540b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "0f052af3cd7085089a8ad10c76eee1939ec03ffd2e303f1328725f5fb8ea42ee", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "VD10 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Ventral D-type Motor Neuron 10. VD10 is a Ventral cord motor neuron, innervates vent body muscles, reciprocal inhibitor. The cell lineage of VD10 is P9.app.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 252, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "699211a9-b31e-46d8-9ff0-53d04da0b4f4": {"__data__": {"id_": "699211a9-b31e-46d8-9ff0-53d04da0b4f4", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a53e89a0-64ee-4840-a357-c9709652ed26", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "f8410ff514ac2858bd0e684a859fbe5de0b7cd58d80673f28774bbebd28efc72", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "VD11 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Ventral D-type Motor Neuron 11. VD11 is a Ventral cord motor neuron, innervates vent body muscles, reciprocal inhibitor. The cell lineage of VD11 is P10.app.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 253, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f514687b-d427-4d3e-979d-4a8e8e92d8bd": {"__data__": {"id_": "f514687b-d427-4d3e-979d-4a8e8e92d8bd", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3b74984e-4c39-4425-8114-6975464333eb", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "4235103ef3901c50035f369fa7297ab4c5bcfd4b78ed1757f9b7282b89fabcbb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "VD12 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Ventral D-type Motor Neuron 12. VD12 is a Ventral cord motor neuron, innervates vent body muscles, reciprocal inhibitor. The cell lineage of VD12 is P11.app.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 253, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c24d4df3-d73d-4c5c-85b3-e0c3bb0d88e8": {"__data__": {"id_": "c24d4df3-d73d-4c5c-85b3-e0c3bb0d88e8", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "28e331bf-9119-4ff6-b9a2-98458a12b783", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "e8e04982de118d9c16ef1d78d76984abca9d6d780ed28e7f4848cd6e42715cd4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "VD13 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Ventral D-type Motor Neuron 13. VD13 is a Ventral cord motor neuron, innervates vent body muscles, reciprocal inhibitor. The cell lineage of VD13 is P12.app.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 253, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ad8d94ef-1b3a-476e-a31a-e630cace77ca": {"__data__": {"id_": "ad8d94ef-1b3a-476e-a31a-e630cace77ca", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2a5c9a81-fb8b-4ed3-8774-10e2e83bcf0a", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "a0409a3741cca38c1a6a97b9ef019ed1c90abdcdaf943b1ecc2af7cb58a8201a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "VD2 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Ventral D-type Motor Neuron 2. VD2 is a Ventral cord motor neuron, innervates vent body muscles, reciprocal inhibitor. The cell lineage of VD2 is P1.app.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 248, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d2ac0244-4b11-427f-8a96-87a9b24a9898": {"__data__": {"id_": "d2ac0244-4b11-427f-8a96-87a9b24a9898", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "dc7a2584-43d9-4087-bcba-5a17d2430178", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "7350a7eb612d226b0dc5c41e43c508abf336e04ae07352456150ffbf2b7d405f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "VD3 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Ventral D-type Motor Neuron 3. VD3 is a Ventral cord motor neuron, innervates vent body muscles, reciprocal inhibitor. The cell lineage of VD3 is P2.app.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 248, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "16875a17-1f45-49f8-b4de-3a49706ef65e": {"__data__": {"id_": "16875a17-1f45-49f8-b4de-3a49706ef65e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f22e61a5-f9d1-46ea-8098-faf29286ee0c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "bbca7fd4a9c88f7b5e2d05912404cb9d5b6a41a0a267cf97fa6e3c8ee9d49708", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "VD4 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Ventral D-type Motor Neuron 4. VD4 is a Ventral cord motor neuron, innervates vent body muscles, reciprocal inhibitor. The cell lineage of VD4 is P3.app.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 248, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "84f4defa-2fe9-4e64-b0ef-f6f1eeb7527b": {"__data__": {"id_": "84f4defa-2fe9-4e64-b0ef-f6f1eeb7527b", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "94a621e2-50fd-40e6-8f08-28a89e303874", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "c18d5e054e15292db7bc0f7c6cda493cf6ec7881431b0b199386794f66598fdf", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "VD5 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Ventral D-type Motor Neuron 5. VD5 is a Ventral cord motor neuron, innervates vent body muscles, reciprocal inhibitor. The cell lineage of VD5 is P4.app.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 248, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "eab62618-85f6-4042-ace1-9583d0058f52": {"__data__": {"id_": "eab62618-85f6-4042-ace1-9583d0058f52", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "299242a1-7797-4f8f-b123-7c17020cb41f", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "252aa97236461cf3daa56c4ddf0951cbc27170971696684906177e690a5568bd", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "VD6 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Ventral D-type Motor Neuron 6. VD6 is a Ventral cord motor neuron, innervates vent body muscles, reciprocal inhibitor. The cell lineage of VD6 is P5.app.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 248, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "93d91590-59cd-40e8-b84f-b822534ec307": {"__data__": {"id_": "93d91590-59cd-40e8-b84f-b822534ec307", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d9856c1a-3716-48b4-aa03-b05ef3edd6e9", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "e8c8ce098426d967ade076e3c0777c64f7ecfc42b70e18f354adbd5f9ed6ed1e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "VD7 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Ventral D-type Motor Neuron 7. VD7 is a Ventral cord motor neuron, innervates vent body muscles, reciprocal inhibitor. The cell lineage of VD7 is P6.app.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 248, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "aeb06081-a523-42d8-a795-05e7c0b11d42": {"__data__": {"id_": "aeb06081-a523-42d8-a795-05e7c0b11d42", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3f3fde79-2fbe-4007-b4c8-180dc56f1a7c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "cefd22997391ce24f09a1dbec2bd67d0c4809c2882140f2b9e8e4b8fd868d8bc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "VD8 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Ventral D-type Motor Neuron 8. VD8 is a Ventralcord motor neuron, innervates vent body muscles, reciprocal inhibitor. The cell lineage of VD8 is P7.app.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 247, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "87446da2-8881-4ed0-bce2-eb9c8a9fc076": {"__data__": {"id_": "87446da2-8881-4ed0-bce2-eb9c8a9fc076", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d8ea7b60-73dc-4239-993d-c7f56a7af58b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "31d800dc0dc973bd450f312db9a0cbfb186f71870592968436ebac56859b7559", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "VD9 is a neuron in the worm C. elegans, of type Ventral cord motor neuron. The name stands for Ventral D-type Motor Neuron 9. VD9 is a Ventral cord motor neuron, innervates vent body muscles, reciprocal inhibitor. The cell lineage of VD9 is P8.app.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 248, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "363b4e9c-c8fa-4ce9-9ff0-3995d03df9a1": {"__data__": {"id_": "363b4e9c-c8fa-4ce9-9ff0-3995d03df9a1", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c20961bc-c405-4b55-8e9a-d80a64bee309", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "28b32a15dfdc5827458263adbf40f745558ec6ddbd6da6a667f9338f9bc967f4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "MCML is a neuron in the worm C. elegans, of type Male head interneuron. The name stands for Mystery Cell of the Male Left. MCML is a Male specific interneuron. The cell lineage of MCML is AmsoL.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 194, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e73ea75c-7016-409b-8713-79c8e1b9718c": {"__data__": {"id_": "e73ea75c-7016-409b-8713-79c8e1b9718c", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "187042f5-81b3-4eec-b623-41f0a20d04e2", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "fbbce4df006b0f21b28bc70b8356ff6fc4b9043ba3476e79d420e84c485951ba", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "MCMR is a neuron in the worm C. elegans, of type Male head interneuron. The name stands for Mystery Cell of the Male Right. MCMR is a Male specific interneuron. The cell lineage of MCMR is AmsoR.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 195, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c292fbd3-2fa6-4d84-8087-6dbc1491934b": {"__data__": {"id_": "c292fbd3-2fa6-4d84-8087-6dbc1491934b", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5b560cf6-6e42-4d1f-9d0f-78e34aab9500", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "33db81388ce299f00a701b9227eb1b8d2fe07eb3b861b9aa04832e1320769172", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PVV is a neuron in the worm C. elegans, of type Male interneuron. The name stands for Posterior Ventral Process V. PVV is a Male specific motor neuron, pre-anal ganglion. The cell lineage of PVV is P11.paaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 207, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b6354a18-ad3f-471f-8b87-aff2ae49d5a8": {"__data__": {"id_": "b6354a18-ad3f-471f-8b87-aff2ae49d5a8", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b75ab8e3-ca7e-456e-99d9-cdaa2ab40ad1", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "d16d9413db88ea4e777d54e5ef89b4e3e5f65f27ba18af61c4e069872af4eeea", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PVX is a neuron in the worm C. elegans, of type Male interneuron. The name stands for Posterior Ventral Process X. PVX is a Male specific interneuron, cell body in pre-anal ganglion, postsynaptic in ring and ventral cord. The cell lineage of PVX is P12.aap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 257, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "674f987f-7e7d-4fd1-b6b2-e8cfc92e547d": {"__data__": {"id_": "674f987f-7e7d-4fd1-b6b2-e8cfc92e547d", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9612eb6d-8b5d-477b-8fbd-c57c1672db45", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "0cef5e79a4c34f40ed5fd7be25cd02fc508a2f48f399b1dd07a377a7b368e8ca", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PVY is a neuron in the worm C. elegans, of type Male interneuron. The name stands for Posterior Ventral Process Y. PVY is a Male specific interneuron, cell body in pre-anal ganglion. The cell lineage of PVY is P11.paap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 219, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fa73b98c-802e-4979-a377-5e5c0c4b2311": {"__data__": {"id_": "fa73b98c-802e-4979-a377-5e5c0c4b2311", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8e4b3b99-3300-4efb-a118-1909c929f57c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "8c56140eef7ae66211d26d0f0a67f95cc6c91deae766ff947bb55564aa59f201", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PVZ is a neuron in the worm C. elegans, of type Male interneuron. The name stands for Posterior Ventral Process Z. PVZ is a Male specific motor neuron, cell body in pre-anal ganglion. The cell lineage of PVZ is P10.ppppa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 221, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0965a4b1-81dc-4294-8599-342c7e6a89ee": {"__data__": {"id_": "0965a4b1-81dc-4294-8599-342c7e6a89ee", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2a729412-3a06-4dad-862e-b456b9353cb6", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "84a585b404cbf8ad49a973bb559283c6e7a341f008c39a292d5441161df06a36", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "DVE is a neuron in the worm C. elegans, of type Male interneuron. The name stands for Dorsorectal Ventral Process E. DVE is a Male specific interneuron, cell body in dorsorectal ganglion. The cell lineage of DVE is B.ppap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 222, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e3a3eef1-0f66-4cdd-b020-a041999b8aa7": {"__data__": {"id_": "e3a3eef1-0f66-4cdd-b020-a041999b8aa7", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "48d3de4b-aa5d-45b9-88e8-52f2465d364e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "91db6cb24aac2639558975f2a70afff9bbf00e71a22eba040015a7706d79a3b4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "DVF is a neuron in the worm C. elegans, of type Male interneuron. The name stands for Dorsorectal Ventral Process F. DVF is a Male specific interneuron, cell body in dorsorectal ganglion. The cell lineage of DVF is B.ppppa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 223, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a1aaf9a1-2123-44a9-b54a-6b6517080917": {"__data__": {"id_": "a1aaf9a1-2123-44a9-b54a-6b6517080917", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2a727c6a-5726-4d8a-acb3-16175a7f8212", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "cf62521b773a00f843b8915633c7156294a4f249cee2e202162900ae3bbb02aa", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "DX1 is a neuron in the worm C. elegans, of type Male interneuron. The cell lineage of DX1 is Male interneuron.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 110, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9fd07e13-d2f0-4fcb-85f4-08c2f7f650bd": {"__data__": {"id_": "9fd07e13-d2f0-4fcb-85f4-08c2f7f650bd", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9de24e33-b045-4049-94e3-2ddd7a1d75ba", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "a9a0d84e507d0e26fe02b61fb26814e750e4804c5ae6e05a371cab50809f6901", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "DX2 is a neuron in the worm C. elegans, of type Male interneuron. The cell lineage of DX2 is Male interneuron.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 110, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8ce698a0-7b37-44ab-bee2-3d7564dbbd41": {"__data__": {"id_": "8ce698a0-7b37-44ab-bee2-3d7564dbbd41", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3c303231-0153-458c-924b-599886d57964", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "69e32b3c37dc16410943ddbcbecf8a162f705699d297cbc83a58b5695f42049f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "DX3 is a neuron in the worm C. elegans, of type Male interneuron. The cell lineage of DX3 is Male interneuron.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 110, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4cd6e06f-3f73-4c60-a9c7-bd3b2ef51c81": {"__data__": {"id_": "4cd6e06f-3f73-4c60-a9c7-bd3b2ef51c81", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b9fcbc85-67fb-4462-82ef-9e9ac60810c3", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "3b1d4757ffbc5561dd793a574e9589a65ecbb9e3fab48a7e25d5dfc4fc04a329", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "EF1 is a neuron in the worm C. elegans, of type Male interneuron. The cell lineage of EF1 is Male interneuron.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 110, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0373c937-8e68-4e36-9957-b66340ef01cc": {"__data__": {"id_": "0373c937-8e68-4e36-9957-b66340ef01cc", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e552eff6-9f91-4c28-976b-88ec5555b0ce", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "2db7d1a88ba2e8b776987471c66ff4f0b9ede52337d28f2c05e3b8c673ccd5d7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "EF2 is a neuron in the worm C. elegans, of type Male interneuron. The cell lineage of EF2 is Male interneuron.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 110, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4864e50b-2e0c-470e-b35b-9d88dfbefacc": {"__data__": {"id_": "4864e50b-2e0c-470e-b35b-9d88dfbefacc", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "448dd345-d604-401e-ac96-2701aa349a64", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "56bd1ea363f34c738bba9963e4563a34f97c58b3a7bfa9372713014982e0e868", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "EF3 is a neuron in the worm C. elegans, of type Male interneuron. The cell lineage of EF3 is Male interneuron.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 110, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9e53d4a9-40f2-4d53-b1dc-701940ec3390": {"__data__": {"id_": "9e53d4a9-40f2-4d53-b1dc-701940ec3390", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "03aaba1a-ce65-45c6-9bbd-499583096f25", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "94132006556ddd5b5b24d9c21c990ac2e5dc6e522132f1393b70824936d731f2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PDC is a neuron in the worm C. elegans, of type Male interneuron. The name stands for Preanal Cell with Dorsal Process C. PDC is a Male specific interneuron, pre-anal ganglion. The cell lineage of PDC is P11.papa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 213, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c722f474-64f1-4c7d-8ca0-a96fc7fd150e": {"__data__": {"id_": "c722f474-64f1-4c7d-8ca0-a96fc7fd150e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9d2d7eb5-4886-4ec1-b158-ffd7cd982250", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "92527241c8a722334a385f9c6f372f71705a3e4ba93d2cd37c7c855c178b7a41", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PGA is a neuron in the worm C. elegans, of type Male interneuron. The name stands for Preanal Ganglion Cell A. PGA is a Male specific interneuron, pre-anal ganglion. The cell lineage of PGA is P11.papp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 202, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "bc4e2eb6-b5da-4737-9f72-42eae6ac8aef": {"__data__": {"id_": "bc4e2eb6-b5da-4737-9f72-42eae6ac8aef", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "15e1e769-7235-4793-9662-79a6cd638925", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "330990f76c85af7896db231b5b5620703a95a7d9c7a7a4d59f29131ab37c74f1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "CA01 is a neuron in the worm C. elegans, of type Male interneuron. The name stands for C-type Neuron, Anterior Daughter after Division 1. CA01 is a Male specific cells, ventral cord, not constructed. The cell lineage of CA01 is P3.aapa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 236, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "abd91342-cd31-4aed-942d-b2dccf3be362": {"__data__": {"id_": "abd91342-cd31-4aed-942d-b2dccf3be362", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0f9eddbd-7b82-4138-a3d2-ac72c719d610", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "dddaeaf3dad1f6068cb55800a595fe3c7d47dc4b19f0148e6fe79e45f2536d02", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "CA02 is a neuron in the worm C. elegans, of type Male interneuron. The name stands for C-type Neuron, Anterior Daughter after Division 2. CA02 is a Male specific cells, ventral cord, not constructed. The cell lineage of CA02 is P4.aapa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 236, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5b8c20a6-4d49-4e38-a816-ce2ddedd7431": {"__data__": {"id_": "5b8c20a6-4d49-4e38-a816-ce2ddedd7431", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d126b747-6c46-4e38-b922-d7a9db8c2c3b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "b013ed67d2e5baec251b81e27e206d04d147ab37a83b92b1bd979df78eb47fc9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "CA03 is a neuron in the worm C. elegans, of type Male interneuron. The name stands for C-type Neuron, Anterior Daughter after Division 3. CA03 is a Male specific cells, ventral cord, not constructed. The cell lineage of CA03 is P5.aapa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 236, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "17c02660-d782-4361-a5cc-b6c141fef5ae": {"__data__": {"id_": "17c02660-d782-4361-a5cc-b6c141fef5ae", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "164c3ed3-418b-4375-9bde-ee6d21bf37bb", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "bd436e3743e9cb342b4017cb5b219b33343a38a61fab423008f0d3f73dd83086", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "CA04 is a neuron in the worm C. elegans, of type Male interneuron. The name stands for C-type Neuron, Anterior Daughter after Division 4. CA04 is a Male specific neuron, ventral cord, innervates dorsal muscles. The cell lineage of CA04 is P6.aapa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 247, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "17ca32c9-d8eb-4ee0-aada-37bac9a01156": {"__data__": {"id_": "17ca32c9-d8eb-4ee0-aada-37bac9a01156", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b853d266-3f82-4b1a-b7cf-e973262a50d4", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "ea728aa51caadded6825d7fb5c702c427cda4930153f0649f1737b7b1ca51be7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "CA05 is a neuron in the worm C. elegans, of type Male interneuron. The name stands for C-type Neuron, Anterior Daughter after Division 5. CA05 is a Male specific neuron, ventral cord, innervates dorsal muscles. The cell lineage of CA05 is P7.aapa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 247, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8db44d49-3e11-405f-9695-762f85881e31": {"__data__": {"id_": "8db44d49-3e11-405f-9695-762f85881e31", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f2c9da62-4ca1-4002-b1ea-b34715992058", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "b472acacbb5f12354e5e2b8dbdf35d2d9abb5cde3742c0651b69087214b61232", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "CA06 is a neuron in the worm C. elegans, of type Male interneuron. The name stands for C-type Neuron, Anterior Daughter after Division 6. CA06 is a Male specific neuron, ventral cord, innervates dorsal muscles. The cell lineage of CA06 is P8.aapa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 247, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6abc9972-157e-4ccc-aa22-a2a6eedbe287": {"__data__": {"id_": "6abc9972-157e-4ccc-aa22-a2a6eedbe287", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c5316da1-4e9a-4b8b-affd-60d429a4ec41", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "a23707917c9c8e01d1ae1cd4bf97c843c74120ebce2382419cc04f74e4216965", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "CA07 is a neuron in the worm C. elegans, of type Male interneuron. The name stands for C-type Neuron, Anterior Daughter after Division 7. CA07 is a Male specific neuron, ventral cord, innervates dorsal muscles. The cell lineage of CA07 is P9.aapa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 247, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2cd2ac7c-67fa-4ae9-99ae-65519f3ae7cf": {"__data__": {"id_": "2cd2ac7c-67fa-4ae9-99ae-65519f3ae7cf", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "91868445-ab34-4dca-bceb-f81b5d7df027", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "99948fc7cbff9b5d90786cbeff8fba1afb60672a91b12812764cf6f01da4694a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "CA08 is a neuron in the worm C. elegans, of type Male interneuron. The name stands for C-type Neuron, Anterior Daughter after Division 8. CA08 is a Male specific cell, ventral cord, neuron-like but lacks synapses. The cell lineage of CA08 is P10.aapa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 251, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "de193fcb-1281-435f-b6c9-e388ff6c6225": {"__data__": {"id_": "de193fcb-1281-435f-b6c9-e388ff6c6225", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3cd3ec05-1354-4b28-b9d6-055eec890419", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "cabe916c2bc2e35906e7a9062518435b15925baeb7231866e7c4f7548ca0b4c4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "CA09 is a neuron in the worm C. elegans, of type Male interneuron. The name stands for C-type Neuron, Anterior Daughter after Division 9. CA09 is a Male specific cell, ventral cord, neuron-like but lacks synapses. The cell lineage of CA09 is P11.aapa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 251, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0ccb6743-90a8-45a2-82c2-23ae50646126": {"__data__": {"id_": "0ccb6743-90a8-45a2-82c2-23ae50646126", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5853f5f2-3c20-45b2-a76b-deb2f92abd4b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "3e1ff251a65596ae1737ec0af7d2bc353e9fdbfc8e5c25db2dee0c961cb16f18", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "CP01 is a neuron in the worm C. elegans, of type Male interneuron. The name stands for C-type Neuron, Posterior Daughter after Division 1. CP01 is a Male specific neuron in ventral cord. The cell lineage of CP01 is P3.aapp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 223, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cddb08a3-d3a1-4043-b193-8a5a29d6eb84": {"__data__": {"id_": "cddb08a3-d3a1-4043-b193-8a5a29d6eb84", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5d3d8de6-6e8e-4dbe-850a-88248d5655ad", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "fe88acd347ea9606e02914c9d6e26d1bd3af33b01d8c362904b145c8e578c308", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "CP02 is a neuron in the worm C. elegans, of type Male interneuron. The name stands for C-type Neuron, Posterior Daughter after Division 2. CP02 is a Male specific neuron in ventral cord. The cell lineage of CP02 is P4.aapp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 223, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "184367f2-6a7e-4bbb-babd-3a8105fc6d54": {"__data__": {"id_": "184367f2-6a7e-4bbb-babd-3a8105fc6d54", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "75b9108f-669c-4c8b-b3cf-753f00e0720a", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "a0c5d33b91fdfb869c68f15baa080cf3b6079dc21bf32124f0e8f3e60f6d6cb7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "CP03 is a neuron in the worm C. elegans, of type Male interneuron. The name stands for C-type Neuron, Posterior Daughter after Division 3. CP03 is a Male specific neuron in ventral cord. The cell lineage of CP03 is P5.aapp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 223, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c3977607-c12a-434f-88dc-ca699199336c": {"__data__": {"id_": "c3977607-c12a-434f-88dc-ca699199336c", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "97d5bb22-69e0-45e7-b0e7-c3f7f7af3b3c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "0a363053d50ff7fcc231427c78b4ed93151b5d50724b96b189d775bdf527f4df", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "CP04 is a neuron in the worm C. elegans, of type Male interneuron. The name stands for C-type Neuron, Posterior Daughter after Division 4. CP04 is a Male specific motor neuron in ventral cord. The cell lineage of CP04 is P6.aapp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 229, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d7317dc5-d90c-4eea-a306-00457ec5f720": {"__data__": {"id_": "d7317dc5-d90c-4eea-a306-00457ec5f720", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e0e6e6eb-73ad-441c-b3ee-9dcede102fa2", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "23d41a86b5cbeb7a38683b007c9ecbdc56e6ef76f2347135bb90619391bb6f8d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "CP05 is a neuron in the worm C. elegans, of type Male interneuron. The name stands for C-type Neuron, Posterior Daughter after Division 5. CP05 is a Male specific motor neuron in ventral cord. The cell lineage of CP05 is P7.aapp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 229, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "eb8ce981-9a0b-47e1-badb-bbdcc2221c85": {"__data__": {"id_": "eb8ce981-9a0b-47e1-badb-bbdcc2221c85", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cd94c671-240d-4507-800c-e071f7f7e12c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "7df1f72aaefa1f202ada3637d21e33f7baeddbe957f01bdf573752e2fe2bba43", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "CP06 is a neuron in the worm C. elegans, of type Male interneuron. The name stands for C-type Neuron, Posterior Daughter after Division 6. CP06 is a Male specific motor neuron in ventral cord. The cell lineage of CP06 is P8.aapp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 229, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "08d2fefd-a687-4c6d-9490-d2a2f3f5213e": {"__data__": {"id_": "08d2fefd-a687-4c6d-9490-d2a2f3f5213e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1d7e2698-8b0a-4d7a-b09e-97b83f3f2eec", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "94d4f0c915a003a092ba8e2773e51ebd3535a4ead01cc2a09161f134cce7418c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "CP07 is a neuron in the worm C. elegans, of type Male interneuron. The name stands for C-type Neuron, Posterior Daughter after Division 7. CP07 is a Male specific motor neuron in ventral cord. The cell lineage of CP07 is P9.aapp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 229, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a5acdbcb-e681-4259-abe0-b87ac363da68": {"__data__": {"id_": "a5acdbcb-e681-4259-abe0-b87ac363da68", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cdbfd566-893d-4b73-a3e5-e8f62660742b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "49945ebf05d5f6aab1510171f2ebee31a30076f714ee61f113b12e4b4115294b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "CP08 is a neuron in the worm C. elegans, of type Male interneuron. The name stands for C-type Neuron, Posterior Daughter after Division 8. CP08 is a Male specific interneuron, projects into preanal ganglion. The cell lineage of CP08 is P10.aapp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 245, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1014ac12-6f81-4244-882c-a59b75595a98": {"__data__": {"id_": "1014ac12-6f81-4244-882c-a59b75595a98", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "156a1d7f-e056-4a2a-b5b1-a58eac518210", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "869d2117066d5e006ea583aaed52dce8e59b3f17a3631cc297adc392a3eb639c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "CP09 is a neuron in the worm C. elegans, of type Male interneuron. The name stands for C-type Neuron, Posterior Daughter after Division 9. CP09 is a Male specific interneuron, projects into preanal ganglion. The cell lineage of CP09 is P11.aapp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 245, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "edf58fe6-f6f7-4af7-8d64-0d1a1beefab3": {"__data__": {"id_": "edf58fe6-f6f7-4af7-8d64-0d1a1beefab3", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "117929b6-8a79-4ec3-a399-0a5752fd7e21", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "0ce86968480a204e7791c554f340d5f33a232cc744c258237293bf69683b51dd", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "CEMDL is a neuron in the worm C. elegans, of type Male head sensory neuron. The name stands for CEphalic Male Sensory Neuron Dorsal Left. CEMDL is a Male specific cephalic neurons (programmed cell death in hermaphrodite embryo) open to outside, possible function in male chemotaxis toward hermaphrodite. The cell lineage of CEMDL is AB plaaaaaap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 346, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f92b0609-da97-4cc1-ba81-d49005c1f873": {"__data__": {"id_": "f92b0609-da97-4cc1-ba81-d49005c1f873", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "778396d0-b56a-445f-91a2-61810e54305f", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "9cee645ad4e9be3c00282069ad7bb90158efa471ed5b33bb8dc84bf1ccc2efa2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "CEMDR is a neuron in the worm C. elegans, of type Male head sensory neuron. The name stands for CEphalic Male Sensory Neuron Dorsal Right. CEMDR is a Male specific cephalic neurons (programmed cell death in hermaphrodite embryo) open to outside, possible function in male chemotaxis toward hermaphrodite. The cell lineage of CEMDR is AB arpapaaap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 347, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "04a26f36-e2f1-4d33-89f9-a8f057f099f4": {"__data__": {"id_": "04a26f36-e2f1-4d33-89f9-a8f057f099f4", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b8adf9fe-c624-423f-b0d0-7b0b23ff739f", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "ae9de323fb48998383c17c5f0e9dd52513589a765f5a59adc611f0f7e532c17b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "CEMVL is a neuron in the worm C. elegans, of type Male head sensory neuron. The name stands for CEphalic Male Sensory Neuron Ventral Left. CEMVL is a Male specific cephalic neurons (programmed cell death in hermaphrodite embryo) open to outside, possible function in male chemotaxis toward hermaphrodite. The cell lineage of CEMVL is AB plpaapapp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 347, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "60db0a3f-3c48-4e57-9bd1-e12295435322": {"__data__": {"id_": "60db0a3f-3c48-4e57-9bd1-e12295435322", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "14e08061-c311-4666-9596-90f73dd7d1e0", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "cf8986e34401cff1ad01bd8f014ef58b1ec248bdbab58cc87609ea4b3235c33b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "CEMVR is a neuron in the worm C. elegans, of type Male head sensory neuron. The name stands for CEphalic Male Sensory Neuron Ventral Right. CEMVR is a Male specific cephalic neurons (programmed cell death in hermaphrodite embryo) open to outside, possible function in male chemotaxis toward hermaphrodite. The cell lineage of CEMVR is AB prpaapapp.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 348, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8dd4d5a9-8040-4de0-bf1b-376e667bdad1": {"__data__": {"id_": "8dd4d5a9-8040-4de0-bf1b-376e667bdad1", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fa24be77-df7a-4880-aab6-87544fbcf6c7", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "c6b1baa839797beb58ee8e0ee31338517235f95eba434517c9f2c04f132c5cd9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "R1AL is a neuron in the worm C. elegans, of type Male sensory neuron. The name stands for Ray 1 Neuron A Left. R1AL is a Male sensory rays, neuron, striated rootlet, cell body in left lumbar ganglion. The cell lineage of R1AL is V5L.pppppaaa, (R1.aaaL).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 253, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6c4d4912-d206-4c6f-9c3a-591b885eabc7": {"__data__": {"id_": "6c4d4912-d206-4c6f-9c3a-591b885eabc7", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fb4380f9-e5d3-4971-94ac-df038efeea5d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "edf3f555e1ac1b7696514b73c3786d025fe46407d1c8542dfe8a94af8a814ed9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "R1AR is a neuron in the worm C. elegans, of type Male sensory neuron. The name stands for Ray 1 Neuron A Right. R1AR is a Male sensory rays, neuron, striated rootlet, cell body in right lumbar ganglion. 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The name stands for Ray 1 Neuron B Left. R1BL is a Male sensory rays, neuron, darkly staining tip, open to outside, cell body in left lumbar ganglion. 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The name stands for Ray 1 Neuron B Right. R1BR is a Male sensory rays, neuron, darkly staining tip, open to outside, cell body in right lumbar ganglion. 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The name stands for Ray 2 Neuron B Left. R2BL is a Male sensory rays, neuron, darkly staining tip, open to outside,cell body in left lumbar ganglion. 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The name stands for Ray 2 Neuron B Right. R2BR is a Male sensory rays, neuron, darkly staining tip, open to outside, cell body in right lumbar ganglion. 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The name stands for Ray 3 Neuron A Left. R3AL is a Male sensory rays, neuron, striated rootlet, cell body in left lumbar ganglion. 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The name stands for Ray 3 Neuron A Right. R3AR is a Male sensory rays, neuron, striated rootlet, cell body in right lumbar ganglion. 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The name stands for Ray 3 Neuron B Left. R3BL is a Male sensory rays, neuron, darkly staining tip, open to outside, cell body in left lumbar ganglion. 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The name stands for Ray 3 Neuron B Right. R3BR is a Male sensory rays, neuron, darkly staining tip, open to outside, cell body in right lumbar ganglion. 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The name stands for Ray 4 Neuron A Left. R4AL is a Male sensory rays, neuron, striated rootlet, cell body in left lumbar ganglion. 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The name stands for Ray 4 Neuron A Right. R4AR is a Male sensory rays, neuron, striated rootlet, cell body in right lumbar ganglion. 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The name stands for Ray 4 Neuron B Left. R4BL is a Male sensory rays, neuron, darkly staining tip, open to outside, cell body in left lumbar ganglion. 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The name stands for Ray 4 Neuron B Right. R4BR is a Male sensory rays, neuron, darkly staining tip, open to outside, cell body in right lumbar ganglion. 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The name stands for Ray 5 Neuron A Left. R5AL is a Male sensory rays, neuron, striated rootlet, cell body in left lumbar ganglion. 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The name stands for Ray 5 Neuron A Right. R5AR is a Male sensory rays, neuron, striated rootlet, cell body in right lumbar ganglion. 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The name stands for Ray 5 Neuron B Left. R5BL is a Male sensory rays, neuron, darkly staining tip, open to outside, cell body in left lumbar ganglion. 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The name stands for Ray 5 Neuron B Right. R5BR is a Male sensory rays, neuron, darkly staining tip, open to outside, cell body in right lumbar ganglion. 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The name stands for Ray 6 Neuron A Left. R6AL is a Male sensory rays, neuron, striated rootlet, cell body in left lumbar ganglion. 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The name stands for Ray 6 Neuron A Right. R6AR is a Male sensory rays, neuron, striated rootlet, cell body in right lumbar ganglion. 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The name stands for Ray 6 Neuron B Left. R6BL is a Male sensory rays, neuron, not darkly staining nor open to outside, cell body in left lumbar ganglion. 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The name stands for Ray 6 Neuron B Right. R6BR is a Male sensory rays, neuron, not darkly staining nor open to outside, cell body in right lumbar ganglion. 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The name stands for Ray 7 Neuron A Left. R7AL is a Male sensory rays, neuron, striated rootlet, cell body in left lumbar ganglion. 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The name stands for Ray 7 Neuron A Right. R7AR is a Male sensory rays, neuron, striated rootlet, cell body in right lumbar ganglion. 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The name stands for Ray 7 Neuron B Left. R7BL is a Male sensory rays, neuron, darkly staining tip, open to outside, cell body in left lumbar ganglion. 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The name stands for Ray 7 Neuron B Right. R7BR is a Male sensory rays, neuron, darkly staining tip, open to outside, cell body in right lumbar ganglion. 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The name stands for Ray 8 Neuron A Left. R8AL is a Male sensory rays, neuron, striated rootlet, cell body in left lumbar ganglion. 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The name stands for Ray 8 Neuron A Right. R8AR is a Male sensory rays, neuron, striated rootlet, cell body in right lumbar ganglion. 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The name stands for Ray 8 Neuron B Left. R8BL is a Male sensory rays, neuron, darkly staining tip, open to outside, cell body in left lumbar ganglion. 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The name stands for Ray 8 Neuron B Right. R8BR is a Male sensory rays, neuron, darkly staining tip, open to outside, cell body in right lumbar ganglion. 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The name stands for Ray 9 Neuron A Left. R9AL is a Male sensory rays, neuron, striated rootlet, cell body in left lumbar ganglion. 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The name stands for Ray 9 Neuron A Right. R9AR is a Male sensory rays, neuron, striated rootlet, cell body in right lumbar ganglion. The cell lineage of R9AR is TR.appapaaa, (R9.aaaR).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 254, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "97e943ad-5b6e-4b0b-9409-e51871a522c2": {"__data__": {"id_": "97e943ad-5b6e-4b0b-9409-e51871a522c2", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6f3e04f5-bb97-4a67-b9f4-1b1bb62deb1a", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "886e8fe20a55be0713fbbd80c96ec3dbfe76296b89c2b9c74d04d310a981897d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "R9BL is a neuron in the worm C. elegans, of type Male sensory neuron. The name stands for Ray 9 Neuron B Left. R9BL is a Male sensory rays, neuron, darkly staining tip, open to outside, cell body in left lumbar ganglion. The cell lineage of R9BL is TL.appapapa, (R9.apaL).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 272, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ab631344-4a9b-4f54-a6cb-e058d3b034a2": {"__data__": {"id_": "ab631344-4a9b-4f54-a6cb-e058d3b034a2", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2994c190-5a94-4243-b9aa-ee5b71c08bdb", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "710b77f0ea29a23abe4f9ea4e8bb4d05a17bde26db2396bdbfa8bb8e1f7207c6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "R9BR is a neuron in the worm C. elegans, of type Male sensory neuron. The name stands for Ray 9 Neuron B Right. R9BR is a Male sensory rays, neuron, darkly staining tip, open to outside, cell body in right lumbar ganglion. The cell lineage of R9BR is TR.appapapa, (R9.apaR).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 274, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6bd0910a-5d05-4fd7-a470-e05427b864a1": {"__data__": {"id_": "6bd0910a-5d05-4fd7-a470-e05427b864a1", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ff0e864e-a4e6-4078-a074-b2fec4088b8b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "c72d6d959e6cc1651b0ccab7c10c7b36f07a460433faf309b312dcb3e8555bcb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PHDL is a neuron in the worm C. elegans, of type Male sensory neuron. The name stands for PHasmid Neuron D Left. PHDL is a Male specific sensory neuron. The cell lineage of PHDL is TL.paa (PHsoL).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 196, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4319d5f7-30cb-4f91-a430-5f2773bf8935": {"__data__": {"id_": "4319d5f7-30cb-4f91-a430-5f2773bf8935", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "71fc883e-7ae5-4434-8eca-b8147f1ed2fd", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "2fecd7647a9adb082894563a1129ceba2f525d3138aabd10b72a60499d5da6fe", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PHDR is a neuron in the worm C. elegans, of type Male sensory neuron. The name stands for PHasmid Neuron D Right. PHDR is a Male specific sensory neuron. The cell lineage of PHDR is TR.paa (PHsoR).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 197, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3027a1e2-cd2a-4824-86ab-b9a050184fc9": {"__data__": {"id_": "3027a1e2-cd2a-4824-86ab-b9a050184fc9", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "99f87289-ecac-472c-8f79-fcd6b86858d6", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "655c673d2841d44a2e9d12a4b81b1b2bbf705c2daea1280410fe3052614864ae", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "HOA is a neuron in the worm C. elegans, of type Male sensory neuron. The name stands for HOok Neuron A. HOA is a Male specific neuron, sensory ending in male hook sensillum, cell body in pre-anal ganglion. The cell lineage of HOA is P10.pppa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 242, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e0c57102-9f5b-468a-ae4b-de7bbab51c93": {"__data__": {"id_": "e0c57102-9f5b-468a-ae4b-de7bbab51c93", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "dcb949b5-a40c-4f95-9ee2-7c97fc006639", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "77f44ca47308f90e790f3c970c0ac711ddea0908557ec654a480baee743a3927", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "HOB is a neuron in the worm C. elegans, of type Male sensory neuron. The name stands for HOok Neuron B. HOB is a Male specific neuron, sensory ending in male hook sensillum, cell body in pre-anal ganglion. The cell lineage of HOB is P10.ppap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 242, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7900ee19-e1b1-49df-8ada-c6f6b80d69fa": {"__data__": {"id_": "7900ee19-e1b1-49df-8ada-c6f6b80d69fa", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a00e52d2-627a-4c4a-ac19-54b39bdb755c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "962b82096b96988e9c6b87fd0cd779f05ca13a43d038e458808158f5909fd1e8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PCAL is a neuron in the worm C. elegans, of type Male sensory neuron. The name stands for PostCloacal Sensilla Neuron A Left. PCAL is a Male specific sensory-motor neuron, sensory ending in male postcloacal sensilla, cell body in left cloacal ganglion. The cell lineage of PCAL is Y.plppd.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 289, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "73f10ed1-1d9b-471e-807e-279fcefa54f3": {"__data__": {"id_": "73f10ed1-1d9b-471e-807e-279fcefa54f3", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "40781c21-b6f3-4d26-a5fb-2c85bd1d1640", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "cd30d3d284fc9d437c87038cd0a9f8940b20ae001a58aa5741f50ccf2f17517d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PCAR is a neuron in the worm C. elegans, of type Male sensory neuron. The name stands for PostCloacal Sensilla Neuron A Right. PCAR is a Male specific sensory-motor neuron, sensory ending in male postcloacal sensilla, cell body in right cloacal ganglion. The cell lineage of PCAR is Y.prppd.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 291, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b6dabd13-6d5e-40a3-b214-e248e22f8542": {"__data__": {"id_": "b6dabd13-6d5e-40a3-b214-e248e22f8542", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "97fc2247-e607-426f-945e-10944359d34c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "530718723d7c13c6090fec2134f584edbd851c0f38cd6b23ee1aade9b55270a0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PCBL is a neuron in the worm C. elegans, of type Male sensory neuron. The name stands for PostCloacal Sensilla Neuron B Left. PCBL is a Male specific sensory-motor neuron, sensory ending in male postcloacal sensilla, cell body in left cloacal ganglion. The cell lineage of PCBL is Y.plpa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 288, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6ce38f85-8bfc-4360-8aef-01586513b868": {"__data__": {"id_": "6ce38f85-8bfc-4360-8aef-01586513b868", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "77040b59-fff1-4066-aabb-6fd0e4e0bc80", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "1c2781242057ef58e62677489b668a48df45f30cd7d772c325dd781e99468050", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PCBR is a neuron in the worm C. elegans, of type Male sensory neuron. The name stands for PostCloacal Sensilla Neuron B Right. PCBR is a Male specific sensory-motor neuron, sensory ending in male postcloacal sensilla, cell body in right cloacal ganglion. The cell lineage of PCBR is Y.prpa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 290, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "bf06cb2f-869b-472d-b296-d0951e672164": {"__data__": {"id_": "bf06cb2f-869b-472d-b296-d0951e672164", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b5ef9f6c-4b09-4af1-a12a-e290d15ca7fb", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "0fc5cf53534dc44243052210efaf24f7e15f66ee4717c7a6d9f466b3901552b7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PCCL is a neuron in the worm C. elegans, of type Male sensory neuron. The name stands for PostCloacal Sensilla Neuron C Left. PCCL is a Male specific sensory-motor neuron, sensory ending in male postcloacal sensilla, cell body in left cloacal ganglion. The cell lineage of PCCL is B.arpaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 290, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cb9ca193-aac9-4419-9e39-e471dfbe2eeb": {"__data__": {"id_": "cb9ca193-aac9-4419-9e39-e471dfbe2eeb", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "73661f14-aa37-48db-8845-b9035af4d454", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "bbfd2fc77f67647617c034b798b5cd861ea3ea397c89a3e3ec1abacf353b1504", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PCCR is a neuron in the worm C. elegans, of type Male sensory neuron. The name stands for PostCloacal Sensilla Neuron C Right. PCCR is a Male specific sensory-motor neuron, sensory ending in male postcloacal sensilla, cell body in right cloacal ganglion. The cell lineage of PCCR is B.alpaaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 292, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fba52a42-94cd-4d45-850f-082614c88ad3": {"__data__": {"id_": "fba52a42-94cd-4d45-850f-082614c88ad3", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8e3f2539-5c3a-43b4-be5f-898f7a2736a5", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "684db301b5d4e5348e5bcb6ec7b4d76b3f98008d0d3fb1096631fa5ba1231a24", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "SPCL is a neuron in the worm C. elegans, of type Male sensory neuron. The name stands for SPicule Neuron C Left. SPCL is a Male specific sensory/motor neuron, innervates spicule protractor muscle, cell body in left cloacal ganglion. The cell lineage of SPCL is B.alpaap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 270, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4437d4bf-c0f0-4660-9a44-7679ee51305f": {"__data__": {"id_": "4437d4bf-c0f0-4660-9a44-7679ee51305f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7b5bab26-77ba-4949-890a-6fa7cf5864a3", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "2f6e3d3d8deb7f0aefe7975d730a2c393590e91c2e92e8da6f297d6749648442", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "SPCR is a neuron in the worm C. elegans, of type Male sensory neuron. The name stands for SPicule Neuron C Right. SPCR is a Male specific sensory/motor neuron, innervates spicule protractor muscle, cell body in right cloacal ganglion. The cell lineage of SPCR is B.arpaap.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 272, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d316b788-fb2e-4b4a-be12-54e8bad8595a": {"__data__": {"id_": "d316b788-fb2e-4b4a-be12-54e8bad8595a", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f743b786-c997-47a5-a4f2-9428bb74dca8", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "ceebf45bce296d47347f5a2397c0245f9082030a68a5751b741f4793ac08de6f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "SPDL is a neuron in the worm C. elegans, of type Male sensory neuron. The name stands for SPicule Neuron D Left. SPDL is a Male specific sensory neuron of male copulatory spicules, ciliated, open to outside at tip of spicule, cell body in left cloacal ganglion. The cell lineage of SPDL is B.alpapaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 300, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0fcb3052-3c2a-4577-8750-24b9629cd29f": {"__data__": {"id_": "0fcb3052-3c2a-4577-8750-24b9629cd29f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "74aae302-5837-4263-aae9-855b145fc9a0", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "2e95bd965d78809f4ce6b618f9a68380d22460d46a8205af55b61eb9c53a47b8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "SPDR is a neuron in the worm C. elegans, of type Male sensory neuron. The name stands for SPicule Neuron D Right. SPDR is a Male specific sensory neuron of male copulatory spicules, ciliated, open to outside at tip of spicule, cell body in right cloacal ganglion. The cell lineage of SPDR is B.arpapaa.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 302, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7f4460c4-79ab-4f1e-870d-33c0a3d6e3b2": {"__data__": {"id_": "7f4460c4-79ab-4f1e-870d-33c0a3d6e3b2", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2db1fc92-c513-454d-a790-41e97a03a67a", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "9cf0e7f641c1538b15fbf4ba5dc771fb84e2c69ae092664a1bc1920fdf6b2039", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "SPVL is a neuron in the worm C. elegans, of type Male sensory neuron. 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The cell lineage of R9shR is Male ray structural cell.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 130, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6b3f9e1c-c2d8-4525-9f7f-500f13cfdcc3": {"__data__": {"id_": "6b3f9e1c-c2d8-4525-9f7f-500f13cfdcc3", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c2b34c59-ff98-4a32-b326-b7f613228df6", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "0457cc354c4cc3a51fa00844ed0a9fb84d14550ca874a5e8bafbaf715b73bb72", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "proctodeum is a neuron in the worm C. elegans, of type Proctodeum (male specific). The cell lineage of proctodeum is Proctodeum (male specific).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 144, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3a226a66-8498-43dd-983d-b729f6355c20": {"__data__": {"id_": "3a226a66-8498-43dd-983d-b729f6355c20", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "75d73a55-dfaf-417c-9ff4-9428b7bc1ede", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [BasicCellInfo, Section Summary information](https://wormatlas.org/neurons/Individual%20Neurons/Neuronframeset.html)"}, "hash": "aa2ae67fb73e86061bab783916cc708da8161a3720111965ed9dbcd3aa2f914e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "gonad is a neuron in the worm C. elegans, of type Gonad (male specific). The cell lineage of gonad is Gonad (male specific).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 124, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b50a163a-b596-426b-a1f4-8d3ddacb45f3": {"__data__": {"id_": "b50a163a-b596-426b-a1f4-8d3ddacb45f3", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Seam cells, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/seam cells/Seamframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e17fca36-8244-47d9-b83e-a36289ad3721", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Seam cells, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/seam cells/Seamframeset.html)"}, "hash": "05bead6ba0616f2ea1d780cce8138f1b7e038a86ab60d220ce19b72549e1baa6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In the adult animal, seam cells are arranged as longitudinal rows of 16 cells on the left and right sides of the body, and they are embedded in the cylindrical hyp 7 syncytium (SeamFIG 1). These cells are also sometimes referred to as lateral hypodermal cells, because they share some functions with the major hypodermis, including secreting cuticle and generating the contractile force during elongation of the embryo. Each seam cell is smoothly tapered in shape. At the cell body, the seam completely interrupts the hypodermis, whereas at its narrow end points, hypodermis runs behind it, covering the seam on the medial side (SeamFIG 2). Seam cells are linked to the hypodermis by small adherens junctions along their apical borders and by small gap junctions on their lateral membranes (SeamFIG 2) (see also Gap Junctions). In a newly hatched animal, there are ten seam cells on each side of the animal (H1-H2, V1-V6 and T). All seam cells, except for H0, divide in a stem-cell-like pattern before each molt. Between the L2 and L4 stages, most seam-cell divisions generate an anterior daughter cell that fuses with hyp 7 and a posterior daughter cell that continues to divide until the last molt between L4 and adult stages (see HypFIG 1). At this final molt, the seam cells exit the cell cycle, differential terminally and fuse to make one longitudinal syncytium (Sulston and Horvitz, 1977; Singh and Sulston, 1976).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1421, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "44b3e0ad-fbdc-4881-a82a-bb2e6c44a768": {"__data__": {"id_": "44b3e0ad-fbdc-4881-a82a-bb2e6c44a768", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Seam cells, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/seam cells/Seamframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e38932d5-ab90-479a-a602-421c129a9c74", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Seam cells, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/seam cells/Seamframeset.html)"}, "hash": "dcca377e52bcc13e7182652b970678854a7ba6af22f31e0c5fb8e865614f48bd", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Similar to the hypodermal cells, seam cells are required for the formation of stage-specific cuticles through synthesis of various collagen proteins (Thein et al., 2003). They also produce alae, a set of raised cuticular ridges that extend longitudinally along the two sides of the animal over the seam cells (SeamFIG 3). Cuticular alae are produced only for the L1 stage, dauer larvae, and adults (DCutFIG 2). There is no alae production in L2, L3 and L4 stages. The adult alae are commonly used as an indicator of hypodermal seam cell terminal differentiation. It has been suggested that longitudinal alae are formed over seam cells during the elongation phase of the embryo by circumferential contraction of the seam cells and seam-specific cuticle  (Singh and Sulston, 1978; Sulston et al., 1983). Alae are formed in cuticle over seam cells as a result of the difference in placement of the circular actin filament bundles within these cells, compared to the ventral and dorsal hypodermal cells (Costa et al., 1997, see Cuticle). Seam cells shrink in cell volume during the formation of the dauer stage, leading to diametric shrinkage of the body and formation of alae (DCutFIG 2 & 3, see Dauer Cuticle) (Singh and Sulston, 1978; Melendez et al., 2003).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1257, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fb91482e-a2e1-4607-950f-3399c7d3f7df": {"__data__": {"id_": "fb91482e-a2e1-4607-950f-3399c7d3f7df", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Seam cells, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/seam cells/Seamframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "711a0e8b-d5bf-42fc-b0ab-d6b3d75f4840", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Seam cells, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/seam cells/Seamframeset.html)"}, "hash": "a6e976dcf1053d4e3dcccc009c25edb872c49b477b745f7def51e194a8bd41ae", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Seam-cell divisions also generate neurons and glia of specific sensilla. During L1, H2.aa becomes an anterior deirid socket (ADEso) cell. During the L2 stage, one of the granddaughters of the V5 cell, V5pa, becomes a neuroblast that produces the posterior deirid sensillum (PDE neuron, PDE sheath cell and PDE socket cell). Seam-cell lineages also give rise to some neurons of lumbar ganglia (PVW and PVN), tail spike neurons (PHC), and support cells of the phasmids (Phso1, Phso2) (Sulston and Horvitz, 1977). In males, V5pp and V6 generate daughters that form sensory rays instead of making alae (Waring and Kenyon, 1990; Hunter et al., 1999; see also Epithelial System of the Male \u00e2\u0080\u0093 Seam and Tail Hypodermis). Tail seam cells on each side (right and left T cells) function as the sockets of the phasmid sensilla in the L1 larva. The opening of the sensillum on each side is sealed by a process that extends from the cell and connects to the sheath cell and hypodermis via adherens junctions (White, 1988). The T-cell lineage ultimately gives rise to phasmid socket cells during later stages of development.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1111, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2c77dec4-8a29-4a22-8352-b03124074e34": {"__data__": {"id_": "2c77dec4-8a29-4a22-8352-b03124074e34", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Seam cells, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/seam cells/Seamframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "69a4559a-0f28-4666-875e-bd9a192986d9", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Seam cells, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/seam cells/Seamframeset.html)"}, "hash": "2e305c4336672b6517755d57b7b59f75cf08c8d0039ab64784f7c9fd5f25cd5c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In animals that have mutations in heterochronic genes, such as lin (lineage abnormal) and some let (lethal) genes, the normal progression of seam cell fate is disrupted (Ambros and Horvitz, 1984; Slack and Ruvkun; 1997; Ambros, 2000). These animals generate seam cells that inappropriately display cell fate patterns of earlier or later stages, resulting in precocious or retarded seam phenotypes (Liu et al., 1995; Abrahante et al., 1998).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 440, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "334b90bc-5b87-477a-9794-5873e3ce93ae": {"__data__": {"id_": "334b90bc-5b87-477a-9794-5873e3ce93ae", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Seam cells, Section 2) Embryonic Development of the Seam Cells](https://www.wormatlas.org/hermaphrodite/seam cells/Seamframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "22e1c516-7936-4835-9563-104774ae528a", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Seam cells, Section 2) Embryonic Development of the Seam Cells](https://www.wormatlas.org/hermaphrodite/seam cells/Seamframeset.html)"}, "hash": "c487bd2a4a22fb3eff24467cc37ac0b9db323f9a8e401c9f1d4fbfeb99e6d7f4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Eighteen of the 20 seam cells of the newly hatched larva are produced around 230-250 minutes after first cell division in the embryo. The mothers of the two V5 cells divide only slightly before hatching to produce V5L/R and QL/R, which give rise to posterior lateral ganglia on each side, post-embryonically. All of the embryonically generated seam cells except H0 are blast cells that undergo further divisions (SeamFIG 4) (Sulston et al., 1983). All derive from the AB lineage and AB.arp by itself gives rise to 12 of them (seven on the right and five on the  left).\u00a0 The characteristic alae seen in L1 appear just before hatching.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 633, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "db65a696-b599-4c69-b00f-fe3cf0ff58bf": {"__data__": {"id_": "db65a696-b599-4c69-b00f-fe3cf0ff58bf", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Seam cells, Section 2) Embryonic Development of the Seam Cells](https://www.wormatlas.org/hermaphrodite/seam cells/Seamframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c9a696f2-94a8-48c8-8801-7cc826115338", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Seam cells, Section 2) Embryonic Development of the Seam Cells](https://www.wormatlas.org/hermaphrodite/seam cells/Seamframeset.html)"}, "hash": "1a673d469f3cd0963a246565853714434b08c7836507f985a7d0ffbaa5fbca74", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Similar to ventral and dorsal hypodermal cells, embryonic seam cells transiently acquire circumferentially oriented actin bundles at the beginning of elongation of the embryo. They are suggested to actively drive hypodermal elongation, whereas dorsal and ventral hypodermal cells change shape passively (SeamFIG 4) (Ding et al., 2004).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 335, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "94edb9b7-3838-46d8-a096-7a478a0be8a9": {"__data__": {"id_": "94edb9b7-3838-46d8-a096-7a478a0be8a9", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Seam cells, Section 3) Post-embryonic Development of Seam Cells](https://www.wormatlas.org/hermaphrodite/seam cells/Seamframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c1be47a0-ca03-4baa-a072-ff041cb72a36", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Seam cells, Section 3) Post-embryonic Development of Seam Cells](https://www.wormatlas.org/hermaphrodite/seam cells/Seamframeset.html)"}, "hash": "85c11dfe29fc8d6ab9e7965d3140e47904ba0f98c7528299e321089812f85a18", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "At hatching, a row of 10 seam cells on each side of the animal are embedded in hyp 7 and are in close contact with the ventral epithelial (P) cells (SeamFIG 4). The seam cells posterior to H0 round up and divide about 5 hours after hatching. The earliest division is seen in V5, whereas H1 and H2 divide 2.5 and 2 hours later, respectively, than the other seam cells (Podbilewicz and White, 1994; Shemer and Podbilewicz, 2000). Around the middle of the L1 stage, the anterior daughters of V2-V6 extend cytoplasmic processes toward the ventral midline, disrupting the adherens junctions between P cells and isolating left-right P-cell pairs from their neighbors (see HypFIG 6B). About 3 hours after birth, the anterior daughters of V1-V6 and T cells, the posterior daughter of H1 (H1p) and H2ap fuse with hyp 7. The posterior daughters of H2, V1-V6, the anterior daughter of H1, and T.ap become the new seam blast cells and extend long thin processes in both longitudinal directions over their presyncytial sisters. These processes establish contact with each other about 8 hours after hatching (see HypFIG 9A) (Austin and Kenyon, 1994).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1136, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2cc0e285-1b58-4de2-a63c-b5cc162dae5b": {"__data__": {"id_": "2cc0e285-1b58-4de2-a63c-b5cc162dae5b", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Seam cells, Section 3) Post-embryonic Development of Seam Cells](https://www.wormatlas.org/hermaphrodite/seam cells/Seamframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2b732f13-6145-4030-b333-9ec63e7dd1fd", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Seam cells, Section 3) Post-embryonic Development of Seam Cells](https://www.wormatlas.org/hermaphrodite/seam cells/Seamframeset.html)"}, "hash": "b8209ae1f0e08d5c153769646c30ded9c84e3a5b17be0124b16ee8b59b7ee49f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The seam cells undergo a stem-cell division again at the beginning of the L2, L3 and L4 larval stages, before molting, repeating the pattern of rounding up, cell division, hypodermal fusion, and reestablishment of contact between seam daughters (SeamFIG 4). This cell\u00e2\u0080\u0093cell contact between seam neighbors has been shown to provide signals for establishment of certain cell fates of seam daughters such as the ray/alae switch in males and post-deirid production in both sexes (Waring et al., 1992). Signaling between V5 and its anterior and posterior neighbors has been shown to be critical for V5 to produce posterior deirid cells (Austin and Kenyon, 1994). About the middle of the L4 stage (around 41 hours after hatching) and after the fusion of 13 anterior daughter cells with hyp 7, 16 seam cells on each side terminally differentiate and fuse with one another (SeamFIG 4). These fusions are the last somatic cell fusions seen in C. elegans.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 946, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9e697135-fa58-4f1b-8323-1f8f8f2bc9a6": {"__data__": {"id_": "9e697135-fa58-4f1b-8323-1f8f8f2bc9a6", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Seam cells, Section 4) List of Seam Cells](https://www.wormatlas.org/hermaphrodite/seam cells/Seamframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a0a74a4f-5e04-4e18-b0c0-1160e7f4c730", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Seam cells, Section 4) List of Seam Cells](https://www.wormatlas.org/hermaphrodite/seam cells/Seamframeset.html)"}, "hash": "ce55c02a4841142e7b895bf851d252ee0dd463fc7f33c897ef02f6a2cd53ae36", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "1. Left side seam cells", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 23, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "156e694e-4e52-4b81-94af-6cf6c9ff06d2": {"__data__": {"id_": "156e694e-4e52-4b81-94af-6cf6c9ff06d2", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Seam cells, Section 1.) Left side seam cells](https://www.wormatlas.org/hermaphrodite/seam cells/Seamframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "854bf12a-c1a2-4c73-a893-301a4f71ed02", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Seam cells, Section 1.) Left side seam cells](https://www.wormatlas.org/hermaphrodite/seam cells/Seamframeset.html)"}, "hash": "45845357fead8842eb2e0cdecaf1981bf564571b675bdde7127aac3dde181ed5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Embryonic (L side) seam cells (do not form a syncytium):\n\nH0L\n\nH1L (postembryonic blast cell)\n\nH2L (postembryonic blast cell)\n\nV1L (postembryonic blast cell)\n\nV2L (postembryonic blast cell)\n\nV3L (postembryonic blast cell)\n\nV4L (postembryonic blast cell)\n\nV5L (postembryonic blast cell)\n\nV6L (postembryonic blast cell)\n\nTL (postembryonic blast cell; functions as phasmid socket in L1)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 383, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "44af14c8-05be-44fc-a910-70dc4826443f": {"__data__": {"id_": "44af14c8-05be-44fc-a910-70dc4826443f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Seam cells, Section 1.) Left side seam cells](https://www.wormatlas.org/hermaphrodite/seam cells/Seamframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "57f6349c-70de-4e49-bcba-f53ca29fdba6", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Seam cells, Section 1.) Left side seam cells](https://www.wormatlas.org/hermaphrodite/seam cells/Seamframeset.html)"}, "hash": "bedb4e22af5c87ee022cf6887025d0d8c092590777ba2c7deafc2ef77b252fda", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Adult (L side ) seam cells (these cells fuse at L4 to make one row of syncytium):\n\nH0L\n\nH1L.aa\n\nH1L.appp\n\nH2L.pppp\n\nV1L.pappp\n\nV1L.ppppp\n\nV2L.pappp\n\nV2L.ppppp\n\nV3L.pappp\n\nV3L.ppppp\n\nV4L.pappp\n\nV4L.ppppp\n\nV5L.ppppp (terminally differentiated as seam only in hermaphrodite; blast cell in male)\n\nV6L.pappp (terminally differentiated as seam only in hermaphrodite; blast cell in male)\n\nV6L.ppppp (terminally differentiated as seam only in hermaphrodite; blast cell in male)\n\nTL.appa (terminally differentiated as seam only in hermaphrodite; blast cell in male)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 556, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c0aa7aaf-e4a7-4e8e-ab70-00426590245d": {"__data__": {"id_": "c0aa7aaf-e4a7-4e8e-ab70-00426590245d", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Seam cells, Section 1.) Left side seam cells](https://www.wormatlas.org/hermaphrodite/seam cells/Seamframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e59cbf4e-b8fe-45bd-bc81-166013ed354a", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Seam cells, Section 1.) Left side seam cells](https://www.wormatlas.org/hermaphrodite/seam cells/Seamframeset.html)"}, "hash": "6fca9d286e40d87c82b9b6de1ac30c7730ee18251365bba30f1dd2f37e82311b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Alternate fate seam cells (L side) in adult male: \n\nV5L.pppapp fuses with the main seam syncytium\n\nV5L.pppppp set cells (male tail seam; does not fuse with main seam and does not make alae)\n\nV6L.papapp set cells (male tail seam; does not fuse with main seam and does not make alae)\n\nV6L.papppp set cells (male tail seam; does not fuse with main seam and does not make alae)\n\nV6L.pppapp set cells (male tail seam; does not fuse with main seam and does not make alae)\n\nV6L.pppppp set cells (male tail seam; does not fuse with main seam and does not make alae)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 557, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "97af0d51-3d3b-4b32-b51e-cf5ce550b173": {"__data__": {"id_": "97af0d51-3d3b-4b32-b51e-cf5ce550b173", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Seam cells, Section 1.) Left side seam cells](https://www.wormatlas.org/hermaphrodite/seam cells/Seamframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b23c8cfd-7b6b-484f-bab4-4a0353f11bcb", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Seam cells, Section 1.) Left side seam cells](https://www.wormatlas.org/hermaphrodite/seam cells/Seamframeset.html)"}, "hash": "d66ebd4018ee689d5d95bb52f6bb69351eff465b881c70b831a005a05f297f21", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "2. Right side seam cells", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 24, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "32332f33-9d92-4279-b388-4d4e470907f7": {"__data__": {"id_": "32332f33-9d92-4279-b388-4d4e470907f7", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Seam cells, Section 2.) Right side seam cells](https://www.wormatlas.org/hermaphrodite/seam cells/Seamframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7d408992-289d-40d4-8b03-b3d113185beb", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Seam cells, Section 2.) Right side seam cells](https://www.wormatlas.org/hermaphrodite/seam cells/Seamframeset.html)"}, "hash": "ee1f1fc15c6e1504f685a8e06df46ff007ba243743e8f7c5a73f4f407116e64a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Embryonic (R side) seam cells (do not form a syncytium):\n\nH0R\n\nH1R (postembryonic blast cell)\n\nH2R (postembryonic blast cell)\n\nV1R (postembryonic blast cell)\n\nV2R (postembryonic blast cell)\n\nV3R (postembryonic blast cell)\n\nV4R (postembryonic blast cell)\n\nV5R (postembryonic blast cell)\n\nV6R (postembryonic blast cell)\n\nTR (postembryonic blast cell; functions as phasmid socket in L1)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 383, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6e2882e7-9a7d-496e-9a6d-639240915448": {"__data__": {"id_": "6e2882e7-9a7d-496e-9a6d-639240915448", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Seam cells, Section 2.) Right side seam cells](https://www.wormatlas.org/hermaphrodite/seam cells/Seamframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d251b4be-beef-459b-ace2-0fbba49a75e0", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Seam cells, Section 2.) Right side seam cells](https://www.wormatlas.org/hermaphrodite/seam cells/Seamframeset.html)"}, "hash": "a6606616626a9263feb9e390996197bb2cb0b5d7063a9f593c70f20969f9d5da", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Adult (R side ) seam cells (these cells fuse at L4 to make one row of syncytium):\n\nH0R\n\nH1R.aa\n\nH1R.appp\n\nH2R.pppp\n\nV1R.pappp\n\nV1R.ppppp\n\nV2R.pappp\n\nV2R.ppppp\n\nV3R.pappp\n\nV3R.ppppp\n\nV4R.pappp\n\nV4R.ppppp\n\nV5R.ppppp (terminally differentiated as seam only in hermaphrodite; blast cell in male)\n\nV6R.pappp (terminally differentiated as seam only in hermaphrodite; blast cell in male)\n\nV6R.ppppp (terminally differentiated as seam only in hermaphrodite; blast cell in male)\n\nTR.appa (terminally differentiated as seam only in hermaphrodite; blast cell in male)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 556, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9589deeb-650e-4aa4-80d9-c8defc9ad24b": {"__data__": {"id_": "9589deeb-650e-4aa4-80d9-c8defc9ad24b", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Seam cells, Section 2.) Right side seam cells](https://www.wormatlas.org/hermaphrodite/seam cells/Seamframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "db28762a-564a-4b04-b426-2716acf90bcd", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Seam cells, Section 2.) Right side seam cells](https://www.wormatlas.org/hermaphrodite/seam cells/Seamframeset.html)"}, "hash": "a2b29c57aa04e974d0355e7cbef05706665c2d233f63c0a3b36a616c5a81fb19", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Alternate fate seam cells (R side) in adult male: \n\nV5R.pppapp fuses with the main seam syncytium\n\nV5R.pppppp set cells (male tail seam; does not fuse with main seam and does not make alae)\n\nV6R.papapp set cells (male tail seam; does not fuse with main seam and does not make alae)\n\nV6R.papppp set cells (male tail seam; does not fuse with main seam and does not make alae)\n\nV6R.pppapp set cells (male tail seam; does not fuse with main seam and does not make alae)\n\nV6R.pppppp set cells (male tail seam; does not fuse with main seam and does not make alae)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 557, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7fbddc0f-f521-4ee3-a451-2b7f01bd2b84": {"__data__": {"id_": "7fbddc0f-f521-4ee3-a451-2b7f01bd2b84", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4e1bd6e1-80ae-4b02-a528-a2d902535719", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "84e7d16684da829ea83f8b3d9e0a712f51ddb1be51e731583242a4bf6f815169", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The adult C. elegans hermaphrodite has 302 neurons that belong to two distinct and independent nervous systems: a large somatic nervous system (282 neurons) and a small pharyngeal nervous system (20 neurons). These systems communicate through a single pair of RIP interneurons (NeuroFIG 1) (Ward et al., 1975; Sulston and Horvitz, 1977; Sulston et al., 1983; White et al., 1986). (For a discussion of the pharyngeal nervous system, see Alimentary System - Pharynx ) The two nervous systems differ in their topologies. In the somatic nervous system, the neurons and their processes are generally positioned between the hypodermis and the body wall muscle and share a basal lamina with the hypodermis that isolates them from the muscles (NeuroFIG 2). In contrast, the pharyngeal neurons lie directly among the pharyngeal muscles and are not separated from their muscle targets by a basal lamina. The neurons in the hermaphrodite have been assigned to 118 distinct classes according to their topology and synaptic connection patterns (White et al., 1986). Cell bodies of most neurons are clustered in ganglia in the head or tail (NeuroFIG 1). C. elegans has 56 neuronal support cells (including the GLR cells; see Muscle System - GLR Cells), which are associated only with the somatic nervous system. The neurons communicate through approximately 6400 chemical synapses, 900 gap junctions, and 1500 neuromuscular junctions (NMJs). Among individual animals, the location of chemical synapses is about 75% reproducible (Durbin, 1987). Every C. elegans neuron name consists of either two or three uppercase letters indicating class and in some cases a number indicating the neuron number within one class. If the neurons are radially symmetrical, each cell has a three-letter name followed by L (left), R (right), D (dorsal), or V (ventral). A complete list of C. elegans neurons, their lineage, and descriptions can be found in the Individual Neuron section of the WormAtlas.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1970, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6c72bba4-e87f-4be6-9ecc-93793e610dd1": {"__data__": {"id_": "6c72bba4-e87f-4be6-9ecc-93793e610dd1", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e3fd0c53-2f23-4a16-a753-89eb4c012815", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "be7103389012bf0949f85388ae5d66028e25b140abb5784cbdc5c39bc52b3fb6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Males have a larger nervous system with 473 cells (with an additional 79 neurons and 36 support cells). Most of these extra, male-specific cells are involved in male mating behavior and are located in the posterior body (Sulston et al., 1980; Lipton and Emmons, 2003; Emmons, 2005). The four CEM (cephalic neuron in male) neurons are an exception; they are located in the head as part of the male cephalic sensilla. The hermaphrodite has only two classes of hermaphrodite-specific neurons: HSN, which are generated in males but go through programmed cell death during early development, and VC neurons, which are derived from the P lineages that give rise to cells of the hook sensillum in males. All of the neurons in both sexes have been individually identified and their lineages described. The connectivity among the hermaphrodite neurons has been established from electron micrographs of serial thin sections, whereas the connectivity of the male nervous system has been the focus of more recent studies (Ward et al., 1975; Ware et al., 1975; White et al., 1986; Durbin, 1987; Hall and Russell, 1991; Chen et al., 2006; see also Male Anatomy.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1147, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "db92187b-2bb0-4eb7-bce2-d821147423ee": {"__data__": {"id_": "db92187b-2bb0-4eb7-bce2-d821147423ee", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c70f2293-ec40-4fde-adfb-84dfa7831397", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "8738474bee3dde522769054cc92d2ffc4fa802c9373417dca949eaaa7f23362b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Despite its compact nervous system, C. elegans is capable of several complex behaviors, in addition to the basics such as locomotion, foraging, feeding, and defecation (de Bono and Maricq, 2005). The animal can discriminate and move toward or away from chemicals, odorants, temperatures, and food sources. It can also detect the presence, density, and sex of nearby nematodes by short-range diffusible signals, by a pheromone, and by changes in oxygen levels (Riddle and Golden, 1982; Cheung et al., 2004; Gray et al., 2004; Jeong et al., 2005; Barr and Garcia, 2006). The animal displays social feeding behavior (de Bono, 2003). Each sex also displays sex-specific behaviors such as egg-laying in hermaphrodites and mating behavior in males (Schafer, 2005). Most of these behaviors are plastic and therefore subject to change through learning and memory (Giles et al., 2006). Additionally, food is a significant modulator of many C. elegans behaviors, including egg-laying, feeding, locomotion, and olfactory behavior, often through serotonin-dependent pathways (Zhang et al., 2005). The neuron circuits that are dedicated to each of these behaviors may communicate via interneurons to produce hierarchies in their execution. For example, in stressful environments where food is scarce, egg-laying behavior is suppressed, whereas after an encounter with food, locomotion behavior becomes suppressed in a starved animal, allowing the animal to feed properly.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1458, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1a404cdb-cb6d-495b-9b76-3ca60edf7a01": {"__data__": {"id_": "1a404cdb-cb6d-495b-9b76-3ca60edf7a01", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2) Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4f5069ea-334d-4d3e-8b87-f62e6707f34c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2) Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "4b685614ccac6bdabf3765c9a3cb97570b36dc83eb86668194a5c0a6b53d6173", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Almost all C. elegans neurons have simple monopolar or bipolar morphologies with mostly unbranched processes that follow nearly identical trajectories in each animal (NeuroFIG 3). A few motor neurons, including VC4 and HSN neurons, make several simple branches as they reach their muscle targets. PVD and FLP neurons are unique in C. elegans because they branch extensively near each body muscle quadrant after early larval stages. Many neurons in the adult male tail are also more highly branched within the preanal ganglion, where some neurons can have four to eight separate branches within the neuropil (S.W. Emmons, J.E. Sulston, D.G. Albertson, M. Xu, and D.H. Hall, unpubl.). Some neuron processes may have pure sensory functions (a dendrite) or pure synaptic output functions (an axon), but many have mixed functions capable of both receiving inputs and sending outputs (a neurite or process).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 901, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7d6c5567-c160-4350-8704-d2dbb11dde33": {"__data__": {"id_": "7d6c5567-c160-4350-8704-d2dbb11dde33", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2) Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b0864be4-fcef-4c65-adf1-a5244b17adb5", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2) Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "27d14f6bec36f2a8796c7216f91782b6b90b7e70614252ac3539cbdeb74d18de", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Neuronal somata are among the smallest in the nematode. In transmission election microscopy (TEM) sections, they are seen as having relatively lightly staining cytoplasm, with a compact nucleus, distinctive rough endoplasmic reticulum (RER), several mitochondria, small clusters of synaptic vesicles, and one or more Golgi bodies. Most of the neuronal nucleus is filled with light-staining \u00e2\u0080\u009ceuchromatin,\u00e2\u0080\u009d with a modest amount of dark \u00e2\u0080\u009cheterochromatin,\u00e2\u0080\u009d and one or more small round nucleoli. Under differential interference contrast (DIC) microscopy, neuronal nuclei can easily be distinguished as small, stippled ovals (NeuroFIG 1). The processes of individual neurons are generally very thin (100\u00e2\u0080\u0093200 nm in diameter), but show local swellings with clusters of vesicles at synaptic regions along the length of the process (White et al., 1986). Within each neurite or major side branch, a small bundle of microtubules (MTs) runs continuously along its length. In addition, each neurite contains a small tube of smooth endoplasmic reticulum (ER) and occasional mitochondria. A few small clusters of free ribosomes sometimes lie within the neurite not far from synapses, either on the presynaptic or post-synaptic side (Rolls et al., 2002). The exact position of synaptic swellings or short side branches is not identical among animals; however, the polarity, handedness, and position of a cell\u00e2\u0080\u0099s main processes are very predictable.\n\n2.1 Nervous System Development 2.1.1 Cell Birth, Programmed Cell Death and Cell Migration", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1533, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4d718fd2-cdc9-4b69-8f5f-5e10aaabfd97": {"__data__": {"id_": "4d718fd2-cdc9-4b69-8f5f-5e10aaabfd97", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.1) Nervous System Development](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c1f2c52b-0636-444b-82e6-d6a538ee3b2c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.1) Nervous System Development](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "acf1dcbd33a5e599d2cc3ec379acd971b1a9c8ad2c019fa8141b4e6933e5c3f9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "C. elegans neurons are generated at three main developmental periods. The first is during the proliferation phase of embryogenesis, the second at the late-L1 stage, and the third at the L2 stage (Sulston and Horvitz, 1977; Sulston et al., 1983). At the time of hatching, the hermaphrodite worm has 222 neurons (202 somatic, 20 pharyngeal) and most of these derive from the AB lineage (the male worm has 224 neurons at this stage). All of the glial cells arise from the AB lineage. MS (six neurons) and C (two neurons) lineages contribute only a few neurons to the nervous system. During late L1, five classes of ventral nerve cord (VNC) motor neurons are generated from P and W lineages (see Postembryonic Neurons Table). Also at this time, additional neurons are generated from Q, G1, H2, T, and K lineages. In the L2 stage, the G2 blast cell divides to give rise to the excretory socket cell and RMF neuron pair, and V5paa generates the cells of the posterior deirids on both sides (see Epithelial system - Hypodermis). In males, the additional neurons that function in male mating are born during the L3 stage (Sulston et al., 1980). As a general rule in C. elegans neurogenesis, most bilaterally symmetric pairs of neurons arise from bilaterally symmetric cell lineages, but there are exceptions to this rule.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1313, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2f2ab07b-02c9-4620-9291-1a93a60f569e": {"__data__": {"id_": "2f2ab07b-02c9-4620-9291-1a93a60f569e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.1) Nervous System Development](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "66adce9a-ad8a-4afd-b022-1ed29f323cc8", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.1) Nervous System Development](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "24d2973a2dd14f2e19a85b63cdf1c342dcdb842e9829649038bf28cd4f68e0dd", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "C. elegans uses programmed cell death in two contexts during neurogenesis: to generate sexual dimorphism in certain parts of the nervous system (death of CEM cells in the hermaphrodite and HSN cells in the male) and to eliminate extra motor neuron production in the VNC. The ap daughters of P3a\u00e2\u0080\u0093P8a become VNC motor neurons, whereas the corresponding cells in the other P lineages die (see Epithelial system - Hypodermis). Similarly, P11aaap and P12aaap are eliminated instead of becoming additional VB cells (Sulston, 1976).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 527, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "de98f464-9313-4cef-9dd7-de9db4bcc5ed": {"__data__": {"id_": "de98f464-9313-4cef-9dd7-de9db4bcc5ed", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.1) Nervous System Development](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e0e88600-aeb3-4294-ad4b-420f33b4ad3d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.1) Nervous System Development](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "66ff8212f7543781e9e23e5c4a7d6554ddfac33d309f97cd00a5c97cdfc3ae1d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Developmentally, neuronal cell movements can be divided into early mass migrations and later individual cell migrations. During embryogenesis, mass neuroblast movements occur to close the ventral cleft (at ~230\u00e2\u0080\u0093290 min after first cell cleavage, dorsal and lateral neurons sink towards inside and adjacent hypodermal cells cover the ventral side). They also occur later at comma stage when anterior neuron groups move toward the tip of the head to form rudiments of the head sensilla (see Epithelial system - Hypodermis). During this time, a sensory depression forms at the tip of the head to provide more surface area for the newly forming sensilla, and later everts (Sulston et al., 1983). Cell bodies of the head sensilla neurons later migrate posteriorly, leaving their dendritic processes stretching behind as attached to the lips. Two extracellular matrix proteins , DYF-7 and DEX-1, are required to anchor these nascent dendritic processes to the lips, since in dyf-7 or dex-1 mutants dendrites remain short and stubby and are dragged along by the neuron cell bodies as they pull away (Heiman & Shaham, 2009). Additionally, the anchoring of dendrites of amphid neurons of each side is highly coordinated, since failure of one dendrite to anchor leads to the failure of attachment of the remaining dendrites of the same side. Subsequent to these events, during elongation, the head neurons are pushed aside as the pharynx grows forward through the mass of neurons surrounding the developing nerve ring (NR). By late embryogenesis, the neurons around the NR settle into their recognizable positions. In later stages, despite the mechanical force generated by body movements, the  organization of cells in head ganglia is mostly maintained through homophilic and heterophilic interactions of cell adhesion molecules expressed on the surfaces of the neurons (Sasakura et al., 2005). There are some exceptions to this however; in live animals, cells can sometimes be seen to flip from one side of the anterior bulb to the other as the pharynx moves (Z. Altun, unpublished observations; White et al., 1986).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2110, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1e912ac8-c7af-4dd8-8eb4-d1ecf9c79f50": {"__data__": {"id_": "1e912ac8-c7af-4dd8-8eb4-d1ecf9c79f50", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.1) Nervous System Development](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "881c0dc5-44e1-43f5-9a42-c35a0498df8e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.1) Nervous System Development](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "3858d6d303edb4051c51661f89ea7f7932df5d055fc48ee3bd48bd56736cdc3b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Although relative positions of cell bodies within ganglia are fairly well conserved between animals of the same developmental stage and genotype, there is still a certain amount of natural variation. These fall into four groups (Z. Altun, unpublished observations; Bargmann and Avery 1996):\n\n 1- posterior lateral ganglia neurons (e.g. AIN, RIC, AIZ, ADEso, AVD)\n\n 2- postembryonic neurons in the tail (e.g. PHC, PLN, PVN, PVW)\n\n 3- postembryonic neurons in the ventral cord (ASn, VAn, VBn, VCn, VDn)\n\n 4- the anterior socket and sheath cells in the head, such as ILsh, ILso, OLQso", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 581, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fcfca6c0-3357-43e4-982c-987df128a960": {"__data__": {"id_": "fcfca6c0-3357-43e4-982c-987df128a960", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.1) Nervous System Development](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f7293fd8-8ed6-4674-b2c4-20aae143988b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.1) Nervous System Development](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "d40e20c06ccbf3e004b6675557454dbdd15840fe5cf138423c004051a14b75db", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The most extreme cases of variability of cell position in the head are seen around the anterior bulb of the pharynx which fits fairly tightly in the body cavity and excludes these cell bodies from its region of maximum diameter. This leads to variability in the position of cell bodies with respect to the bulb. For example, in the N2U animal, OLQsoDL lies anterior to the bulb, whereas its symmetrical partner, OLQsoDR, lies posterior to the bulb (White et al., 1986).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 469, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "023a1973-ab16-4e8c-ad2b-8f0f169d5635": {"__data__": {"id_": "023a1973-ab16-4e8c-ad2b-8f0f169d5635", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.1) Nervous System Development](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "24bcf69d-22b8-4ee8-abd4-9ad63aa54ae9", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.1) Nervous System Development](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "97cb2afd2fa242e9f3e3ae50d5e38ee1fe9fc19707e5a9f2e35b9f38aca8c54c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Most neurons are born close to their ultimate positions and need migrate only short distances. However, there are a few neurons that must migrate long distances after they are born (NeuroFIG 4A,B) (Hedgecock et al., 1987; Montell, 1999). This group includes canal-associated neurons (CAN), which move from the anterior end to a location midway along the body; HSN neurons, which move from the posterior end to close to the vulva; and anterior lateral microtubule (ALM) neurons, which move posteriorly from the anterior edge of the intestine to midway within the anterior body. QR and QL neuroblasts also migrate extensively (NeuroFIG 4). QR and QL are born about 1 hour before hatching at symmetric locations on the right and left sides of the posterior body, respectively, but after cell migrations their terminally differentiated progeny reside in nonsymmetric positions. Soon after hatching, QR migrates anteriorly, whereas QL migrates posteriorly. Their descendents continue migrating asymmetrically to anterior positions on the right side and posterior positions on the left (Salser and Kenyon, 1992). Each Q lineage produces a mechanosensory neuron (AVM/PVM), a sensory neuron (AQR/PQR), an interneuron (SDQR/L), and two programmed cell deaths.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1250, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0f167b05-34d1-4ca8-a591-8d641e6406c0": {"__data__": {"id_": "0f167b05-34d1-4ca8-a591-8d641e6406c0", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.1) Nervous System Development](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6bb0268e-90bf-4bea-93eb-58f7594463ef", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.1) Nervous System Development](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "b32ecf8fe857890b9b1ca19b6bd6497d1f064dc5b7a9687163e1521d1d0df641", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Some neurons display delayed maturation during development. The Y cell functions as a rectal epithelial cell until early larval stages, but later becomes terminally differentiated as PDA in the hermaphrodite. The embryonically born HSN neurons develop synapses onto newly born sex muscles only in the L3 and L4 stages (White et al., 1986). Similarly, VC neurons branch onto sex muscles in the L4 stage. DD motor neurons acquire their final synaptic connection pattern at the late-L1 stage, after the birth of VD neurons, and AVM neurons become connected to the anterior touch circuit at the late-L4 stage (Chalfie and White, 1988; Walthall et al., 1993).\n\n2.1.2 Process Outgrowth, Establishment of Process Tracts and Guidance at the Midline", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 740, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "57e34b2a-90de-4813-9669-f2a3c8322a05": {"__data__": {"id_": "57e34b2a-90de-4813-9669-f2a3c8322a05", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.1) Nervous System Development](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9e9a8913-e030-4555-9c5d-4f59386d1861", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.1) Nervous System Development](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "06879b8089c2fd37037d21001f3ad637f80fda853b9dde507fa5878ffa31a2e0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The nervous system of C. elegans displays handedness at many places. First, although the majority of neurons are in pairs and localize on the right and left sides of the animal in a bilaterally symmetric manner, there are many unilaterally placed single neurons. Additionally, members of some neuron pairs, such as SDQL/SDQR and AQR/PQR, are positioned far away from one another in a nonsymmetrical manner (NeuroFIG 4). Second, the two major cords of the animal, the VNC and dorsal cord (DC), are asymmetrical in their composition or location (NeuroFIG 4 and NeuroFIG 5). The DC is located at the left side of the dorsal hypodermal ridge, whereas the VNC has a thick fascicle on the right side of the ventral hypodermal ridge and a thin fascicle on the left. Third, the neurons in the body choose the side of the body on which to send their processes; although the pair of HSN neurons extends its neurites ipsilaterally along the two VNC tracts, many neuron pairs, such as PVD and PDE, have both of their neurites in the right tract, which requires the left-sided process to cross the midline. Similarly, the VNC motor neurons, which are localized at the midline, make \u00e2\u0080\u009cchoices\u00e2\u0080\u009d regarding the side on which to grow their circumferential processes, whereas all of them extend their ventral processes along the right VNC tract. The right fascicle of the VNC is further populated by some NR processes that exit the NR on the left side, but then decussate to the right to continue extending within the VNC (NeuroFIG 5, top panel right side and panel C) (White et al., 1986).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1574, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "82f9a876-28a8-4cb5-aa01-d3536aa05b81": {"__data__": {"id_": "82f9a876-28a8-4cb5-aa01-d3536aa05b81", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.1) Nervous System Development](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7c07e63a-a2e2-4d5e-88a0-a0a717dda97d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.1) Nervous System Development](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "8de392beeeb14fa312571dafa13a2ffe13de52d00cde6dd138f55d4a7ad2e53e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Asymmetry within the C. elegans VNC is established embryonically by pioneer neurons and midline cues provided by neuronal and nonneuronal (e.g., hypodermal and glial) tissues (NeuroFIG 4). AVG and PVT neurons mark the anterior and posterior boundaries of the VNC. AVG is the anterior guidepost neuron that pioneers the right tract of the VNC, whereas PVPR pioneers the left tract from the posterior, followed by the PVQL process (Durbin, 1987; Wadsworth and Hedgecock, 1996; Wadsworth et al., 1996). PVQ axons pioneer the lumber commissures and continue to travel alongside the PVP processes in the VNC. Although the PVPR axon is absolutely required for proper outgrowth of left-tract neurites, the AVG axon is essential for the correct outgrowth of only a subset of processes into the right tract (Hutter, 2003; Hutter et al., 2005). PVT, a single neuron in the preanal ganglion, serves as a guidepost neuron to growing axons from the lumbar ganglia in the posterior of the VNC. When PVT is ablated embryonically, these axons follow multiple routes to enter the VNC instead of making tight bundles in the two lumbar commissures (Wadsworth et al., 1996; Antebi et al., 1997; Ren et al., 1999). PVT is also required for maintenance of neurite architecture in the VNC post-embryonically, because in the absence of PVT, embryonically generated neurites are unable to maintain their positioning along the cord at the L1 stage and erroneously cross over the midline into the opposite fascicle (Aurelio et al., 2002; Hobert and B\u00c3\u00bclow, 2003). BDU processes are required for correct positioning of AVM branches in the NR (Chalfie and White, 1988). Notably, RIF neurons, which are the first processes to cross the ventral midline between the NR and the beginning of the VNC, are not essential for providing the pathway for guiding processes into the right VNC fascicle at the anterior decussation (Durbin, 1987; Hutter, 2003). The two neuron pairs, which decussate shortly after RIF, SABVs, and RIGs, are also not essential for this function.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2034, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2e2624b4-3315-43b1-988e-cf23a7af307f": {"__data__": {"id_": "2e2624b4-3315-43b1-988e-cf23a7af307f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.1) Nervous System Development](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9425b15d-31a4-4733-8b67-c10d9cf88f67", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.1) Nervous System Development](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "c7c2ae2976c7d32bd1975f337a29a144f3bb9e74e38e699eddcaf8bb5536aab7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Of the 302 neurons in the adult hermaphrodite,180 project axons/processes into the NR. In the developing embryo, these axons that form the nerve ring must navigate to the NR within commissural and longitudinal nerve bundles, recognize the region of the NR, make L/R side choices to enter the NR, make specific contacts with each other to form synapses and maintain these contacts during later growth. Additionally, head and neck muscle development has to be coordinated with the longitudinal and commissural tract and nerve ring development. Currently, little is known about the procession and control of the NR development. Based on studies of embryos at 350 min and 430 min (after first cleavage,) it has been suggested that SIBD neurons act as pioneers to might provide a substrate for the formation of early amphid commissure, while RIH and RMEV might help navigate the first axons entering the NR from the ventral side (Norris, C., Hall, D. H., Hedgecock, E. unpublished observations) (NeuroFIG 15-2).  In the early neurula, head muscle cells directly surround the pharynx where the NR will form and hence may restrict the access of lateral axons to reach the NR until the muscle cells move dorsally and ventrally to the periphery to their usual positions next to the hypodermis. As they migrate, they are suggested to leave railing processes behind attached to the NR, forming the arms of the head muscles (see Somatic Muscle).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1433, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "317dcbe1-0d6c-4343-bfe6-8a9a6407f2f6": {"__data__": {"id_": "317dcbe1-0d6c-4343-bfe6-8a9a6407f2f6", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.1) Nervous System Development](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "66a97407-c8a3-439a-baac-22ee518c3a6e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.1) Nervous System Development](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "752ab202c71cf5adcbb983799dfa291c3d24a57e8feb5715650010ab05e2b6d1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Outgrowth, branching, and shaping of neuronal processes, which are dependent on intrinsic cytoskeletal dynamics and extrinsic cues, are highly stereotyped in C. elegans. Mutant studies have uncovered several genes that seem to be involved in proper process outgrowth and suppression of excess axon branching (Altun-Gultekin et al., 2001; Knobel et al., 2001; B\u00c3\u00bclow et al., 2002). Neurons that extend commissures use the classical UNC-6/netrin and SLT-1/slit pathways, which act redundantly, as well as additional pathways that act in parallel to these, for circumferential guidance along the dorsoventral axis (for review, see Chisholm and Jin, 2005). Intrinsically, cytoskeletal rearrangements are regulated by Rac GTPases and the actin-binding protein UNC-115 (Yang and Lundquist, 2005). Extracellularly, guidance cues are modified by heparan sulfate proteoglycans, which affect neurite branching and patterning in a cellular context-dependent manner (B\u00c3\u00bclow and Hobert, 2006.) Although the mechanisms for branch-point control are still unclear, branching generally occurs under four circumstances: (1) Processes may enter midway along an existing nerve and bifurcate and grow in both directions; (2) processes are confronted with two equivalent neighborhoods, such as the entrance to the NR, and they may split and grow into both; (3) within the NR, processes may also bifurcate to enter two different neighborhoods; and finally, (4) processes in longitudinal nerves may bifurcate and grow a branch circumferentially into another nerve (Hedgecock et al., 1987).\n\n 2.1.3 Developmental Plasticity", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1598, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "983c073e-973e-4e81-a6ea-2ecc11e8cb92": {"__data__": {"id_": "983c073e-973e-4e81-a6ea-2ecc11e8cb92", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.1) Nervous System Development](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "006849fc-4e9d-401c-a0c6-9864f374ec85", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.1) Nervous System Development](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "f190052a5998a8a52713f720bdf37010a456f39a67c623409e99dabe15f190d8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The C. elegans nervous system exhibits various forms of plasticity as it matures. At the end of the L1 stage, post-embryonically born body wall muscles and five classes of newly born motor neurons are incorporated into the existing motor system and novel neuromuscular junctions are established, suggesting reciprocal responsiveness between the muscles and motor neurons. The end of the first larval stage also marks the rewiring of the synaptic contacts of DD motor neurons after the birth of VD motor neurons. This rewiring is intrinsically controlled and is not dependent on VD, VA, or VB neurons (White et al., 1978). Additionally, the neurons maintain similar densities of synapses during the fivefold increase in body length as the animal goes through four larval stages, suggesting that the nervous system maintains a certain level of plasticity throughout life and adjusts itself to the overall growth.\n\n2.2 Neuron Categories", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 933, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "794a654e-5dfc-460b-a306-36651a9db568": {"__data__": {"id_": "794a654e-5dfc-460b-a306-36651a9db568", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.2) Neuron Categories](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4e667db6-b726-4573-b89d-a65ac78d9e0e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.2) Neuron Categories](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "ca6ab136afed3dec1fa58baa3d722b2b7e7852f23e37920a16792a22733541e5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "C. elegans neurons fall into four functional categories defined by their circuitry: (1) motor neurons, which make synaptic contacts onto muscle cells; (2) sensory neurons, which have obvious sensory specializations (behavioral or mutant paradigms now demonstrate defined sensory functions for most of these cells, but some cells only have inferred or yet obscure sensory capabilities; NeuroTABLE 1); (3) interneurons, which receive incoming synapses from and send outgoing synapses onto other neurons; and (4) polymodal neurons, which perform more than one of these functional modalities. A pair of pharyngeal neurons, NSML/R, have prominent secretory terminals and are classified as neurosecretory neurons (they also have motor function; see Alimentary System - Pharynx). Besides these categories, there is a small subset of neurons whose functions are yet unknown. Some of these may be more important in process guidance or maintenance than in circuitry (Durbin, 1987; Chen et al., 2006; Hall et al., 2006).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1009, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "57d651a7-1654-49e4-86b3-52e091a5d529": {"__data__": {"id_": "57d651a7-1654-49e4-86b3-52e091a5d529", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.3) Motor Neurons and the Motor Circuit](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "166f79b4-9e7a-4da5-abd8-39a5257b898b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.3) Motor Neurons and the Motor Circuit](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "e78db98a58ada85d3e73ee44b669262fbda07c90e417e6063403f2edfc3c27bc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The locomotory behavior repertory of C. elegans includes \"crawling\" on solid surfaces and \"swimming/thrashing\" in liquid media. A total of 113 of the 302 C. elegans neurons belong to the motor neuron category, and they control crawling and swimming behaviors as well as the motility of the alimentary and reproductive systems. Of these 113, 75 innervate 79 body wall muscles posterior to the head (16 neck and 63 body muscles) and belong to eight distinct classes (AS, DA, DB, DD, VA, VB, VC, and VD) (NeuroFIG 6, NeuroFIG 7 and NeuroFIG 8). A- and B-type motor neurons (VA, VB, DA, DB, AS) are cholinergic and stimulatory. D-type motor neurons (VD, DD) secrete \u00ce\u00b3-aminobutyric acid (are GABAergic) and are inhibitory and strictly post-synaptic to other motor neurons. VC motor neurons express several transmitters and their primary targets are vulval muscles. VA, VB, VC, and VD classes innervate ventral muscles, whereas DA, DB, DD, and AS classes innervate the dorsal muscles by sending commissures to the dorsal side (White et al., 1976, 1986).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1048, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "593a73c2-9862-4bfa-97ca-d5b02e5c8c45": {"__data__": {"id_": "593a73c2-9862-4bfa-97ca-d5b02e5c8c45", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.3) Motor Neurons and the Motor Circuit](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "aefc25a0-c226-4314-ab9f-033034ba3468", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.3) Motor Neurons and the Motor Circuit](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "8dc69dc0d4758233280fe9b0c79ffe04d7130802493db106163ed979c23b8fdb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The VNC neurons regulate the characteristic undulatory movement of the animal, which involves alternate contraction of the dorsal and ventral longitudinal muscle rows. These motor neurons synapse onto either both dorsal or both ventral muscle quadrants, thereby restricting the body\u00e2\u0080\u0099s flexures to the dorsoventral plane, creating sinusoidal waves as the animal lies on its lateral side on the substrate. When the dorsal muscles are activated, the ventral muscles are reciprocally inhibited and vice versa. Bending against the substrate results in forward locomotion as a result of propagation of sequential contraction and relaxation waves passing backward along the body. D-type motor neurons have processes that are post-synaptic corecipients at the dyadic NMJs of stimulatory (A- or B-type) motor neurons, and the ventral D and dorsal D neurons work as reciprocal cross-inhibitors. Their GABAergic synaptic outputs are onto diametrically opposite muscles, so that when a ventral or dorsal muscle group is activated by a cholinergic motor neuron, the opposite group of muscles is inhibited and relaxed (NeuroFIG 6) (White et al., 1978; McIntire et al., 1993). D-type motor neurons are most important for resetting the animal\u00e2\u0080\u0099s posture, for example, when reversing direction or initiating rapid movement (Jorgensen and Nonet, 1995; Jorgensen, 2006). In response to a touch, an animal that lacks GABA input shrinks due to unopposed contraction of both dorsal and ventral muscles. Once an animal gets moving, GABA input does not interfere with wave propagation; however, it does affect the amplitude of the body waves.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1621, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c67ef27d-301c-4fa7-a6d4-0f393281198a": {"__data__": {"id_": "c67ef27d-301c-4fa7-a6d4-0f393281198a", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.3) Motor Neurons and the Motor Circuit](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cf67c562-873b-4923-b0ba-2dbfe870f2b4", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.3) Motor Neurons and the Motor Circuit](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "db0c43982fc41394868183819b60cf03afcbd6ffd73d62f139879808edc67402", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Movement in either forward or reverse directions is regulated by signals from specific classes of command interneurons (NeuroFIG 6A). Forward motion is promoted by input from AVB and PVC interneurons onto DB and VB neurons, whereas backward motion is promoted by input from AVA, AVD, and AVE interneurons onto DA and VA neurons (NeuroFIG 6) (Chalfie and White, 1988; Driscoll and Kaplan, 1997; Von Stetina et al., 2006). Synaptic innervation of motor neurons by command interneurons occurs throughout the length of the VNC. Command interneurons establish the direction of locomotion, but are not thought to be involved in wave propagation down the length of the animal (Jorgensen and Nonet, 1995). It is currently unclear which neurons are involved in wave propagation, although proprioceptive inputs are thought to have a role. The command interneurons are not equivalent because ablation of AVA or AVB produces uncoordinated animals (after a bout of forward or backward motion, animals kink while trying to reverse their direction) that are touch responsive, whereas ablation of PVC or AVD mainly abolishes the touch-mediated locomotory responses, but does not result in any change in spontaneous locomotion (Chalfie et al. 1985).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1232, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c32c33d2-6f50-4b1a-9346-6e46b206aac4": {"__data__": {"id_": "c32c33d2-6f50-4b1a-9346-6e46b206aac4", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.3) Motor Neurons and the Motor Circuit](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "29e824ee-8f7f-46ac-9a75-105bdf40a090", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.3) Motor Neurons and the Motor Circuit](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "e425f29e95bbfefe0b0ba9be0b79be7a6a28954e4d9bbb4648457b5e9f14df79", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The members of each class of body motor neurons are evenly distributed along the length of the ventral cord between the retrovesicular ganglion (RVG) and preanal ganglion (PAG). They create a longitudinal, synaptic fate map onto the body muscles (NeuroFIG 6C, NeuroFIG 7 and NeuroFIG 8). Within each class of motor neurons there is little or no overlap in the output regions of adjacent members (White et al., 1976). The cell bodies of motor neurons are covered by the hypodermal basal lamina and lie on top of the ventral hypodermal ridge or are wedged between the ridge and the processes of the right tract of the VNC.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 620, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b14ede89-7748-40e6-a5c5-3141ebe50d73": {"__data__": {"id_": "b14ede89-7748-40e6-a5c5-3141ebe50d73", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.3) Motor Neurons and the Motor Circuit](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9f8da904-31a6-4212-8677-3a823bd00238", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.3) Motor Neurons and the Motor Circuit](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "4210ca8118784613a46b602ddc636552e9ad06531be922ba1f359f81fb5b61ba", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Motor neurons are generated at two distinct developmental stages: first, around midembryogenesis and then, during the first larval stage (Sulston and Horvitz, 1977; Sulston et al., 1983). DA, DB, and DD are the only classes of motor neuron present in the VNC at hatching. They are born at midembryogenesis and simultaneously extend commissures to the DC. Command interneurons that make synapses onto them enter the VNC after motor neuron outgrowth is completed. During the L1 stage, DA and DB innervate dorsal muscles and DD innervates ventral muscles. DD dendrites receive input from DA and DB at dyadic synapses onto the dorsal muscle arms. After hatching, the other five classes (additional 56 motor neurons) are generated by 13 (W and Pn) blast cells (see Epithelial System - Hypodermis ). The anterior daughters of the first division of P cells (Pna) give rise to 53 of these (Sulston et al., 1983). The processes from these later-born cells insert themselves into the cord between existing fibers to establish contacts with appropriate command interneurons and muscle cells. After post-embryonic motor neurons are born, DD neurons reverse their synaptic polarity without undergoing any structural change in process placement (White et al., 1978). They rearrange their synaptic machinery to receive input from the nascent VA and VB motor neurons and send output to dorsal muscles. An additional excitatory class of neurons, SABVL/VR/D, innervates anterior ventral body muscles only in the L1 stage; after this stage, they function as interneurons.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1552, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "16dc1f24-d0df-4d7a-90b9-21ec83cc088d": {"__data__": {"id_": "16dc1f24-d0df-4d7a-90b9-21ec83cc088d", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.3) Motor Neurons and the Motor Circuit](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2424b9de-7ac0-439f-8a02-bd93c7f52498", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.3) Motor Neurons and the Motor Circuit](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "f8ce5b14aeae2591b738d8fc0972063f122ca0a267dd68dfeff6cba29adbe997", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Unlike the body, the head of the animal is capable of making lateral movements as well as dorsoventral flexures, especially during foraging behavior. Head and neck muscles are innervated by about 11 classes of motor neurons in the NR in a complex pattern (see Somatic Muscle). Additional nerve\u00e2\u0080\u0093muscle contacts occur along the length of the sublateral cords (J. Duerr et al., unpubl.). Most axons in these nerve cords show periodic swellings filled with synaptic vesicles and sometimes have small presynaptic densities. The post-synaptic targets of these synaptic release zones are possibly the body muscles. The specialized motor neurons of the alimentary and reproductive systems that are associated with defecation and egg-laying muscles are discussed the Alimentary System - Rectum and Anus and Reproductive System - Egg-laying apparatus sections, respectively.\n\n2.4 Sensory Neurons", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 887, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ecd3b8ed-6d39-4320-b0d4-470fba3214ce": {"__data__": {"id_": "ecd3b8ed-6d39-4320-b0d4-470fba3214ce", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "da959dcf-5b29-4f77-8102-a5e3b45106f5", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "5a9b87759133321f1b55d4f9a9036a72d8263ba8090149fc029bde0d7bbee964", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "C. elegans explores its environment and moves to favorable surroundings by chemotaxis, thermotaxis, and aerotaxis and escapes from harmful and noxious stimuli by avoidance/escape behaviors. The perception of environmental cues, including mechanical stimuli, temperature, many water-soluble and volatile chemicals, noxious substances, ambient osmolarity, oxygen levels, pH, and light, is accomplished through 24 sensillar organs and various isolated sensory neurons (NeuroTABLE 1) (Bargmann, 2006; Bergamasco and Bazzicalupo, 2006). Sensillar neurons perform most of the sensory functions. However, some sensory functions, including oxygen sensation and mechanosensation, are performed by nonsensillar neurons. Each sensillum contains ciliated endings of one or more neurons and often two types of glia: the socket cells and the sheath cells. Except for posterior deirids and phasmids, all sensilla are located in the head (see Neuronal Support Cells and Introduction; IntroTABLE 1).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 982, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "495ad15e-eb03-4e32-a373-4ecb9becd72f": {"__data__": {"id_": "495ad15e-eb03-4e32-a373-4ecb9becd72f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "31a1985b-63b8-4747-86a8-9be827642a1c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "73bd6b8ccc65300a9c08e2ecb1faaed1794a423ad4716b1ad482cc3a28521830", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Through the function of these neurons, C. elegans navigates thermal, chemical, and oxygen gradients by modulating the probability of its turning behavior and speed of movement on a solid surface. Turning can be produced either by a reversal of movement followed by resumption of forward movement in a new direction or by omega turns in which the animals curl their whole body so that their heads get close to or even touch their tails before starting to move forward (NeuroFIG 6) (Pierce-Shimomura et al., 1999). Alternatively, the animal can accelerate its forward-directed movement after receiving a sensory signal.\n\n 2.4.1 Mechanosensation", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 642, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c73a1b62-3519-4ed1-a87d-e33489931778": {"__data__": {"id_": "c73a1b62-3519-4ed1-a87d-e33489931778", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c33647ac-f635-4a87-9b65-26d30055b08e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "f7633f9f57705c3e08edf6842ab4ca976b3d8c83510b89040076ee0c85cb8472", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Mechanical stimuli, including gentle touch along the body (e.g., with a soft hair), gentle touch to the nose, harsh touch along the body (e.g., with a wire), and tapping of the culture plate, are perceived through touch receptors and proprioceptors that fall into three classes according to their cytoskeletal specialization: (1) mechanoceptors with ciliated sensory endings; (2) touch receptor neurons containing large-diameter, 15-protofilament microtubules (also called MT cells); and (3) neurons with processes containing synapse-free stretches and undifferentiated cytoskeletons (NeuroTABLE 1) (Herman, 1995; Driscoll and Kaplan, 1997; Syntichaki and Tavernarakis, 2004; Goodman, 2006; O\u00e2\u0080\u0099Hagan and Chalfie, 2006). Mechanociliary neurons display features important for sensing any mechanical deflections over the worm\u00e2\u0080\u0099s surface; IL1, CEP, OLL, OLQ, ADE, and PDE cilia terminate embedded within the cuticle, and all of them except for IL1 are anchored in this cuticle by small electron-dense nubbins. Additionally, the distal sections of ADE, PDE, OLL, and CEP cilia contain an amorphous, dark, microtubule-associated material (TAM) that is also found in mechanocilia of other species. IL1 cilia contain a dark-membrane-attached disc at their tips. All mechanosensory stimuli lead to avoidance responses in the hermaphrodite. \n\n Mechanosensory neurons detect force through mechanically-gated ion channels which produce touch- or stretch-evoked currents. These channels are generally formed by two protein superfamilies; the TRP channels which are nonspecific cation channels composed of subunits with six transmembrane \u00ce\u00b1 helices, and heterotrimeric DEG/ENaC channels which are permeable to sodium and sometimes to calcium (Arnadottir and Chalfie, 2010; Bounoutas and Chalfie, 2007; Kahn-Kirby and Bargmann, 2006). The C. elegans genome encodes 28 predicted DEG/ENaC proteins and 23 predicted TRP proteins(Goodman & Schwarz, 2003).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1938, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "84495146-4f3a-49de-a763-18302da62c8c": {"__data__": {"id_": "84495146-4f3a-49de-a763-18302da62c8c", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ab635b4c-1b09-4dd4-8eb2-aec5df9452f1", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "83e1d9500e66e046b3ba7405de57fcca5b2cf449dea6c521a5b17f0a00ccd05d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "ALM and PLM cells are born during embryogenesis. ALM cells migrate posteriorly, a process that is completed before the elongation stage of the embryo (Sulston et al., 1983; Chalfie, 1993). In newly hatched larvae, the processes of these touch cells are located between the lateral hypodermis and the adjacent muscle quadrant. At about 12 hours post-hatching, they become engulfed by the adjacent hypodermis (Chalfie, 1993). Two other touch receptor neurons, AVM and PVM, are born post-embryonically about 9 hours after hatching at 20\u00c2\u00b0C. Their processes run anteriorly within the VNC at its extreme ventral edge (NeuroFIG 5).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 625, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2acdc692-f9d8-4208-aaf0-36d9c56c0033": {"__data__": {"id_": "2acdc692-f9d8-4208-aaf0-36d9c56c0033", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5182293c-aa91-45fb-b6c3-043569156239", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "72e8b814044384b315264a728c4337d8a99e5803581beb718baba35d10956471", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Each touch neuron process is 400\u00e2\u0080\u0093500 \u00ce\u00bcm long in the adult and is filled with large-diameter (30 nm), 10- to 20-\u00ce\u00bcm-long, 15-protofilament MTs that overlap and bundle together through cross-links (Chalfie and Thomson, 1979, 1982). The tubulin dimers MEC-12 (\u00ce\u00b1-tubulin) and MEC-7 (\u00ce\u00b2-tubulin) coassemble into these 15-protofilament structures (Fukushige et al., 1999). At hatching, ALM and PLM cells contain fewer and shorter MTs. By 12 hours, MTs start to increase in number and length and, by 36\u00e2\u0080\u009348 hours, adult levels are reached (Chalfie and Thomson, 1979, 1982).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 571, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f9c28e53-e6da-41ee-b86b-f91c546f77ac": {"__data__": {"id_": "f9c28e53-e6da-41ee-b86b-f91c546f77ac", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7ff0f84b-e99f-47a1-a428-5bbc798a6f7e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "5d2f4528f4737669effa26ba785d5da2cdb6fa7172b73b1f5c21fb51b97d2efc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The touch receptor neurons also transduce the plate-tap response, which is considered to involve a nonlocalized touch stimulus. In the tap response, signals from the anterior touch circuit (the producer of backward movement) tend to override those from the posterior one, causing animals to reverse direction or move backward in response to a tap to the culture plate. This preference becomes especially strong at L4\u00e2\u0080\u0093adult transition (approximately 46\u00e2\u0080\u009351 hours post-hatching) when the late-developing AVM becomes connected to the anterior touch circuit by forming an inhibitory connection to the AVB interneurons (Chalfie and Sulston, 1981; Walthall and Chalfie, 1988; Chiba and Rankin, 1990).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 697, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6d7ec8f2-85d0-43be-8909-bb6e89b89b03": {"__data__": {"id_": "6d7ec8f2-85d0-43be-8909-bb6e89b89b03", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ae757d1a-ce41-4390-8c3c-785f621e9aa1", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "3ba8fda574b5107afed61dea9468b280b333c9f410f6748ff548f0aad8c5a705", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Touch sensation modifies other behaviors of the animal; for example, gentle body touch regulates pharyngeal pumping and egg-laying and resets the defecation cycle. These responses may be elicited by the synapses between the touch neurons and CEPs, deirid neurons, HSN motor neurons, and RIP interneurons (Syntichaki and Tavernarakis, 2004).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 340, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "20073466-b1a4-4ec8-9496-0b2a20eec33c": {"__data__": {"id_": "20073466-b1a4-4ec8-9496-0b2a20eec33c", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "55c3610b-7b74-4b7b-9ab1-25b641e24673", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "e30a91d5be2102f94045b9521d94a0d052992c948d12b18766d5b382e3c36f6d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Harsh (high threshold) body touch. In the absence of all touch receptor neurons, the animal still retains the ability to respond to harsh touch along the body (e.g., with a wire), and this response can be eliminated by killing the PVD cells (recent results suggest ALM neurons also sense harsh touch (Chatzigeorgiou et al., 2010)). Hence, PVD neurons, which are presynaptic to command interneurons AVA and PVC, are proposed to be the mechanoceptors for harsh body touch (Way and Chalfie, 1989). In adult animals, PVD neurons show extensive branching along the body wall, from the tail to the neck of the animal, covering dorsal and ventral territories (NeuroFIG 3 and NeuroFIG 10) (Halevi et al., 2002). Multiple short branches arise from the main branches at the level of the muscle quadrants and these branches give rise to further branches subventrally and subdorsally. The molecules needed for mechanotransduction of harsh touch are not well known (O\u00e2\u0080\u0099Hagan and Chalfie, 2006). mec-3 mutant animals, in which PVD neurons do not differentiate properly, retain the ability to respond to harsh touch to the head and tail (Way and Chalfie, 1989; Tsalik et al., 2003; O\u00e2\u0080\u0099Hagan and Chalfie, 2006). A harsh touch defect in the tail is seen in the absence of PVC neurons, which may be sensing the stimulus directly or indirectly through other neurons (NeuroFIG 10C).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1364, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b709035b-9d8c-43fa-8fb5-a2811ca8753e": {"__data__": {"id_": "b709035b-9d8c-43fa-8fb5-a2811ca8753e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7406cd3f-e2a4-45e0-a112-69a449b20359", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "4b762d25a0e8c59db079d70af362ca21b098886c5af52c408e061019887af5ec", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Harsh (high threshold) head/nose touch. Three classes of neurons, FLP, ASH, and OLQ, form ciliated endings in the nose, which transduce head-on nose touch stimuli that results in reversal of movement (NeuroFIG 10) (Kaplan and Horvitz, 1993). FLP neurons have a similar branching pattern to PVDs in the head (topologically they complement; where PVD branches end in the neck, FLP branches start) and act together with ASH neurons to sense harsh mechanical stimuli to the head (Albeg et al., 2011; Chatzigeorgiou and Schafer, 2011). OLQs may enhance this mechanoreception (NeuroFIG 10A). ASH and FLP neurons are coupled to the locomotion circuitry via gap junctions and chemical synapses made onto AVA, AVB, and AVD interneurons.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 727, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8c1d745f-a8d2-4752-9634-c7b4d01877f2": {"__data__": {"id_": "8c1d745f-a8d2-4752-9634-c7b4d01877f2", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "694ea69b-8728-4de9-9bef-68c2da81f18e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "06b0616805532731291548f7063798a6f8ad3c28db5a1466acf05abea5a94aa6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Gentle (low threshold) nose touch. Two classes of neurons, OLQ and IL1, function in aversive head-withdrawal reflex and suppression of lateral foraging movements of the head in response to gentle touch on the ventral or dorsal tip of the nose (Hart et al., 1995). IL1 and OLQ synapse onto NR motor neurons, and IL1 makes direct synapses onto head muscles. OLQ may also function in mechanosensory feedback for foraging, as the rate and amplitude of foraging in unstimulated animals is affected in OLQ-ablated animals. FLP neurons also respond to gentle nose touch and activate an escape behavior (Chatzigeorgiou and Schafer, 2011). OLQ and CEP neurons indirectly facilitate gentle nose touch responses in the FLP head nociceptors via the RIH interneuron which acts as the integrating neuron of this circuit hub(Chatzigeorgiou and Schafer, 2011).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 844, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1bf6a699-4c27-4c91-9245-34865c1107b9": {"__data__": {"id_": "1bf6a699-4c27-4c91-9245-34865c1107b9", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c98b969f-e488-4636-b1dd-21f70727e006", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "93de051f6f7dabb19c7260e1c1d9e869ae6660d767f6cd90095670fe85e2cf27", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Texture sensation. C. elegans can sense mechanical attributes of the surface material on which it navigates through the function of dopaminergic CEP, ADE, and PDE neurons (NeuroFIG 10) (Sawin et al., 2000). The capability to distinguish texture (e.g., small, round objects) helps animals to detect food in their environment, in addition to olfactory cues, and causes slowing of locomotion (food-induced slowing response).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 421, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ab623308-ddb2-4a8b-b6af-a8b211cf34d6": {"__data__": {"id_": "ab623308-ddb2-4a8b-b6af-a8b211cf34d6", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "455dfe18-1d1c-4bea-8237-5f3365ccd859", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "a25800dfcb947c788e1e2fd57665ba9055970564540a6904242327a30fff3132", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Proprioception. Worms may sense changes in stretch and tension within their own bodies, especially during locomotion. Some neuron processes with morphologically nonspecialized, synapse-free, bare-wire portions are thought to transduce proprioceptive stimuli. Such properties have been hypothesized for many neurons, including the A- and B-type motor neurons, PHC, some pharyngeal neurons, and male tail neurons (NeuroFIG 6) (Hall, 1977; Sulston et al., 1980; Albertson and Thomson, 1984; Hall and Russell, 1991; R. Lints and D.H. Hall, unpubl.). Some of these may function to sense the degree of bending during undulatory movement, providing sensory feedback about the worm\u00e2\u0080\u0099s body posture and coordinating the degree and timing of alternating contractions and relaxations of muscles (White et al., 1986; Tavernarakis et al., 1997). A similar proprioceptive property has been proven for the DVA neuron, in which stretch sensitivity is transduced by the trp-4 membrane channel (Li et al., 2006). The DVA axon travels from its cell body in the tail anteriorly to the NR via the VNC, but it is not known to show any specializations by TEM that mark its stretch-sensitive portion. PVD may have a role in proprioception, as ablation of PVD leads to defective posture (Albeg et al., 2011). PVD and DVA neurons are presynaptic to both forward and backing command interneurons and provide input to both anterior and posterior touch circuits to maintain overall activity of the circuits. Animals lacking these neurons respond to tap stimulus with diminished forward accelerations and reversals, and mutation of the trp-4 channel or laser ablation of DVA gives rise to animals with body bending defects (Wicks et al., 1996; Driscoll\u00a0 and Kaplan, 1997; Li et al., 2006).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1760, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ed6a3b5a-3250-4311-8d3f-26371c4516e9": {"__data__": {"id_": "ed6a3b5a-3250-4311-8d3f-26371c4516e9", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "38a9f151-9a30-4949-ab69-08785ad2668d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "cf2a9b5a265f06171465500cd9525b052fdd20c06c8a452242bfb9c956b812bb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Body wall muscles may also sense the degree of stretch within them and modulate the contractions required for organized locomotion (Liu et al., 1996). Putative \u00e2\u0080\u009cproprioceptive\u00e2\u0080\u009d endings in the pharynx are fastened by AJs or hemi-AJs to the pharyngeal cuticle (I1, I2, I3, I6), pharyngeal muscle specializations near the lumen (M3, NSM), or a muscle cell soma (I5) (Albertson and Thomson, 1976). Physiological experiments support that a few of these pharyngeal neurons may be stretch sensitive (Avery and Thomas, 1997).\n\n 2.4.2 Nociception", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 541, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4115923d-e735-4b1c-9c2c-f935d23aaf30": {"__data__": {"id_": "4115923d-e735-4b1c-9c2c-f935d23aaf30", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b5a0964c-ea7b-4bdd-b7c0-7c1596bdc776", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "68fa71570006bd882afe59e9749c696ca56047c4dd7dbf7f981a4533eaef3ef8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Nociception is the ability to recognize toxic and harmful components in the environment that allows for avoidance and survival. For C. elegans, aversive cues include mechanical stimuli (both light and harsh touch), certain odorants and toxic chemicals, high osmotic strength, acidic pH, extremes of heat and cold (see thermonociception below), and certain light wavelengths (Culotti and Russell, 1978; Tobin and Bargmann, 2004). Many of the chemicals that are noxious for C. elegans are toxic or bitter for other animals as well, including sodium dodecyl sulfate (SDS), quinine, and heavy metals such as copper (Sambongi et al., 1999; Tobin and Bargmann, 2004). It should be noted that animals in diapause are much more stress-tolerant, including heat-shock conditions (Wittenburg and Baumeister, 1999, see Dauer chapter). ASH neurons are polymodal nociceptors that detect nose touch, high osmotic strength (high concentration of salts or sugars), acidic pH, quinine and other bitter compounds, heavy metals, and aversive odors such as 2octanone, octanol, and benzaldehyde (NeuroTABLE 1). ASH neurons have cilia exposed to the outside and generate a rapid escape response in the form of reversal and turning upon encountering noxious stimuli (NeuroFIG 6) ( et al., 1986; Troemel et al., 1997; Hart et al., 1999). All ASH-mediated sensory behaviors require the TRPV channels OSM-9 and OCR-2 (Tobin et al., 2002). The diverse array of nociceptive cues sensed by ASH neurons generate distinct amplitudes and patterns of glutamate release from these neurons onto the target command interneurons that allow separable behavioral responses (Mellem et al., 2002).\n\n2.4.3 Chemosensation and Odorsensation", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1695, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6397fd31-6f28-4d49-add5-e14c4563bd51": {"__data__": {"id_": "6397fd31-6f28-4d49-add5-e14c4563bd51", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "293fa182-82aa-4125-bb31-92b24db437f3", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "d4ead605d3a879863bac5b11719b76b16a2b7f486727e7fc029f283e2c966bb4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "C. elegans can detect and discriminate a wide range of chemical compounds, including water-soluble chemicals (chemosensation or gustatory sensation) such as anions, cations, cyclic nucleotides, biotin, and amino acids and volatile chemicals (odorsensation or olfactory sensation) such as alcohols, aldehydes, ketones, esters, pyrazines, thiazoles, and aromatic compounds (Bargmann and Mori, 1997; Mori, 1999; Bargmann, 2006). There are 32 chemo/odorsensory neurons that fall into 14 classes. Of these, 22 are paired neurons of the amphid sensilla, four are paired neurons of the phasmid sensilla, and six are IL2 neurons of the inner labial sensilla (NeuroTABLE 1; see Neuronal Support Cells). Most of the individual amphid neurons detect either water-soluble or volatile chemicals and direct either attraction or aversion, although lower concentrations of certain chemicals may be sensed as attractive, whereas higher concentrations may become repellent. A few neurons may sense both attractive and aversive cues (NeuroTABLE 1) (Bargmann and Horvitz, 1991; Bargmann et al., 1993; Troemel et al., 1997).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1103, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c3041a2b-3b8d-442d-955e-3911e6057778": {"__data__": {"id_": "c3041a2b-3b8d-442d-955e-3911e6057778", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "db8f7586-58f4-4e74-8aa6-1a5047b83a29", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "9a1b73aff6a748bd2f679a74e540b157b44d65ec205338fec8321f440e1bf2c1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The ADF, ASE, ASG, ASI, ASJ, and ASK neurons mediate chemotaxis to water-soluble attractants. Among these, ASE seems to be the main sensor, with others having weaker roles. ASE is also unique because the two ASE neurons have distinct functions; the ASER preferentially detects chloride and potassium ions, whereas the ASEL preferentially senses sodium ions (Pierce-Shimomura et al., 2001). ASH neurons are the main nociceptors and mediate avoidance from water-soluble and volatile cues. ASH is complemented by other amphid neurons in these functions; ADL neurons contribute to osmosensation and avoidance from octanol, copper, and cadmium, whereas ASK and ASE contribute to avoidance of SDS and to cadmium and copper, respectively (Sambongi et al., 1999; Hilliard et al., 2002). ASJ neurons participate in formation and recovery by detecting dauer-inducing (dauer pheromone) and dauer-suppressing (food) signals in different developmental stages. ADF, ASI, and ASG function to inhibit dauer formation under favorable conditions (Bargmann and Horvitz, 1991). The three \u00e2\u0080\u009cwing\u00e2\u0080\u009d cells AWA, AWB, and AWC sense volatile chemicals, and each neuron is preferentially linked to a particular behavioral response (Wes and Bargmann, 2001). Whereas AWC and AWA mediate odortaxis to volatile attractants, AWB detects aversive odorants important for long-range escape behavior.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1366, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e34cc44f-7304-4eca-a655-94f8c290ed51": {"__data__": {"id_": "e34cc44f-7304-4eca-a655-94f8c290ed51", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7ec7143f-2f93-4093-a7fb-750287234965", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "9706ae60c9be030bb77d0645285ef3d9eafe6297e834aa2ed2d4bcc318eff554", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "As described above, C. elegans lies on either of its sides and moves either forward or backward using a sinusoidal-like undulation by alternately contracting its body wall muscles along the ventral and dorsal surface. Most of the time, the animals simply move forward (smooth runs), but this forward locomotion is occasionally interrupted by a number of processes such as omega-turns, pirouettes and gentle turning. During an omega-turn the worm makes a deep bend with the worm\u00e2\u0080\u0099s head often contacting its tail, before the animal returns to forward motion along a new heading. Pirouettes are a series of reversals with one or more omega-turns that allow the worm to make major re-orientations in its direction of movement. Gentle turns (steering) are generated when the worm gradually changes its heading by a biased head swing during forward locomotion. Pirouettes appear to occur randomly, while steering appears to be a more directional process. Chemotaxis is driven by gently steering up the gradient as the wormmoves forward and by altering the probability of pirouette initiation by which runs toward lower concentration are interrupted, whereas runs toward the attractant are sustained, eventually biasing the locomotion toward the higher concentration of the chemical (Appelby, 2012; Pierce-Shimomura et al., 1999; Iino and Yoshida, 2009).\n\n 2.4.4 Thermosensation", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1373, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cc9b24d0-f617-4ef2-92ec-e244b1671a16": {"__data__": {"id_": "cc9b24d0-f617-4ef2-92ec-e244b1671a16", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "529ad9a7-ce0d-4560-9c94-f1fd922023d3", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "18fb41a623b1db4786a45f669ae9c5482f87d51cf747649a22462dde9bda940f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "As a cold-blooded soil nematode, C. elegans can tolerate a limited temperature range (~12-27\u00c2\u00b0C) at which it is both fertile and viable (Hedgecock and Russell, 1975). C. elegans can accurately detect temperatures within this range, and this is reflected in its thermotactic behavior. Following cultivation with food at temperatures ranging from 15\u00c2\u00b0C to 25\u00c2\u00b0C, it migrates to the cultivation temperature on a temperature gradient and continues to move isothermally at that temperature. In contrast, the animals disperse away from the temperature at which they were previously starved (Hedgecock and Russell, 1975; Mori, 1999). This thermal preference/avoidance behavior is plastic and can be reset to a new temperature associated with presence/absence of food within 2\u00e2\u0080\u00934 hours of cultivation at that temperature. Through thermotactic behavior, C. elegans can escape unfavorable environments and regulate its position in the upper levels of soil, which may display large vertical and temporal temperature gradients. Behaviorally, C. elegans migrates towards its preferred temperature by modulating its turning rate and run length as a function of temperature change. Once it reaches within 3\u00c2\u00b0C of its preferred temperature, it can fine-tune its tracking to 0.05\u00c2\u00b0C differences by constantly reorienting its head movement (Ryu and Samuel, 2002; de Bono and Maricq, 2005)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1371, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d2ebc22b-fa6d-4db5-be6b-6dc0b1b7a0df": {"__data__": {"id_": "d2ebc22b-fa6d-4db5-be6b-6dc0b1b7a0df", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2fa39847-9060-4934-8fda-a00a194f92fc", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "275195d677c12d74c7b44f288328be5834b799c5c45d575aa04da216c99e6616", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "There are three thermosensors in C. elegans; the amphid AFD neurons (also called \u00e2\u0080\u009cfinger\u00e2\u0080\u009d cells) are the major thermosensors (NeuroTABLE 1; see Neuronal Supportal Cells), while the amphid AWC and ASI neurons are supportive (Mori and Ohshima, 1995; Kuhara et al, 2008; Ohnishi et al, 2011; Beverly et al, 2011). AFD neurons have complex, brushlike structures at their dendritic ends that are completely embedded in the amphid sheath. Animals in which AFDs are killed are athermotactic. TAX-6 (calcineurin), three receptor-type guanylyl cyclases which function redundantly (GCY-8, GCY-18, and GCY-23), and cGMP-dependent TAX-2/TAX-4 cation channel have been shown to be involved in thermosensation in AFD (Kuhara et al., 2002; Inada et al., 2006). When tax-6 is mutated, animals display a thermophilic phenotype, whereas gcy-23 , gcy-8, and gcy-18 triple mutants show a cryophilic or athermotactic phenotype. In AWC, heterotrimeric G-protein signaling and cGMP-dependent TAX-4 cation channel are involved. In the current model for thermosensation, the downstream AIY interneuron is bidirectionally regulated by AFD and AWC. Thermosensory information is transmitted from AFD and AWC to AIY through EAT-4/VGLUT-dependent glutamatergic neurotransmission. Glutamatergic signals from AFD inhibit AIY via activation of GLC3 (glutamate-gated chloride channel) and induce migration towards colder temperature. Glutamatergic signals from AWC, on the other hand, stimulate AIY to induce migration towards warmer temperature (Kuhara et al, 2008; Ohnishi et al, 2011). When AI Y are killed animals become cryophilic and migrate to colder temperatures than the cultivation temperatures, while ablation of AIZ neurons, which are the main postsynaptic target of AIY, makes animals thermophilic and induce them to migrate to warmer temperatures (Mori, 1999).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1844, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "434d373e-7418-448b-972b-a3a8a036c536": {"__data__": {"id_": "434d373e-7418-448b-972b-a3a8a036c536", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "41d6f336-1a4e-466c-91e2-e58f95796140", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "017ab169aa0df049595c6dfdcaae57e84abbe75ed8aa4d7b868aa6954e1d5283", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "C. elegans also reacts to noxious (extreme cold or hot) temperatures. A prolonged exposure at 30\u00c2\u00b0C results in an induction of the heat-shock response and the animals cease egg-laying within a few hours (Lithgow et al., 1995), but resume reproduction if returned to lower temperatures (Aprison and Ruvinsky, 2014). Behaviorally, when they encounter a noxious heat source they respond with a reflexive withdrawal reaction (thermal avoidance response) (Liu et al., 2012; Wittenburg and Baumeister, 1999). PVD neurons in the body respond to acute cold shock, while AFD and FLP neurons in the head and PHC neurons in the tail sense noxious high temperatures (~35-38oC) (Chatzigeorgiou et al., 2010). This nociceptive heat response utilizes a different neural circuit than thermotaxis and the response of C. elegans to noxious high heat is modulated by glutamate and by the neuropeptides encoded in the flp-1 locus. Two channel protein families contribute to thermonociception in C. elegans in distinct neurons: the TAX-2/TAX-4 cyclic nucleotide-gated channels and thermal-gated TRPV channels (TRPA, TRPM and TRPV ion channel families are considered \"thermoTRPs\"; the gating of these channels by temperature is facilitated by chemical signals)(Hall & Treinin, 2011). Upon encountering noxious heat, TAX-2 and TAX-4 become activated in AFD neurons by cGMP which is mainly generated through the activity of GCY-12, but also to a lesser extent by GCY-8/18/23. In FLP and PHC neurons thermonociceptive signal transduction involves the OCR-2 and OSM-9 TRPV channels which can assemble into a heteromultimeric channel complex. PVD response to cold requires TRPA-1 channel (Chatzigeorgiou et al., 2010). \n\n 2.4.5 Light Sensation", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1716, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "87e60474-3023-4d73-a99a-40ceaf62da01": {"__data__": {"id_": "87e60474-3023-4d73-a99a-40ceaf62da01", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5938de27-9585-4152-bff0-3e067a9508ff", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "7624702d4946d8666911296cec2aa5a9c22d6639fd1b66c982c28c911d73d677", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Light stimuli induce a photophobic, movement-reversal response in C. elegans. Recently, it has been found that this response peaks in the high-energy ultraviolet (UV) range (blue-violet) and the head sensory neurons are apparently not required for this behavior (Burr, 1985; K. Miller, pers. comm.). It is suggested that the response originates in the VNC, although the exact sensory mechanism is yet to be described.\n\n2.4.6 Oxygen and Carbon dioxide Sensation", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 460, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ef098110-3b19-4d16-aab1-43b64e96fdaf": {"__data__": {"id_": "ef098110-3b19-4d16-aab1-43b64e96fdaf", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "050d7a62-3afd-4cba-8ecd-72f6ae717848", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "427b61bfa30eaaab39e07f8e5b54a5c7147f0171b45d5956a67fc510d792487e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "C. elegans lacks a specialized respiratory system and uses diffusion for gas exchange. It can sustain a normal rate of metabolism between 2% and 21% ambient oxygen due to diffusion of oxygen to its tissues through the pseudocoelomic fluid, in which all tissues bathe (Van Voorhies and Ward, 2000). When cultivated under standard laboratory conditions, with a linear gradient from anoxia to atmospheric oxygen in the gas phase, C. elegans rapidly moves to an intermediate preferred oxygen concentration of between 7% and 14% oxygen, avoiding both high and low oxygen levels, although this response can be modified by environment and experience (Gray et al., 2004; Cheung et al., 2005; Rogers et al., 2006). In the wild, C. elegans lives close to decaying organic matter where it is exposed to an air/water interface with rapidly shifting oxygen tensions (0\u00e2\u0080\u009321%) due to consumption of oxygen by microbes. Ambient oxygen levels may, therefore, be perceived as indicating the presence of food by this animal. Oxygen sensation is performed by a distributed network of neurons that includes AQR, PQR, and URX, possibly gcy-35-expressing SDQ, ALN, and BDU, and osm-9-expressing (nociceptive) ADF and ASH neurons (White et al., 1986; Gray et al., 2004; Chang et al., 2006). AQR, PQR, and URX may perform a head-to-tail oxygen comparison achieved through their positions along the body in close contact with the pseudocoelom because they are suggested to function to monitor the pseudocoelomic fluid, including its oxygen content (NeuroFIG 11) (Rogers et al., 2006). AQR is a right-sided neuron, derived post-embryonically from the QR blast cell; PQR is a left-sided neuron, derived post-embryonically from the QL blast cell. Both have ciliated endings. The AQR ending is free within the pseudocoleomic cavity, whereas the PQR ending lies close to the pseudocoelom, but is wrapped by the phasmid socket cell (see Neuronal Supportal Cells). URX cell bodies lie within the pseudocoelomic cavity. Similar to URX, AQR, and PQR neurons, SDQ, BDU, ALN, and PLN express soluble guanylate cyclases (sGC) that bind to molecular oxygen, consistent with a primary oxygen-sensing function for these AQR neurons. SDQs are also similar in lineage, morphology, and neural connectivity to the AQR and PQR neurons. Additionally, nociceptive ADF and ASH neurons may be modulatory or respond to oxygen directly. The output of the aerotaxis neuron network converges on AVA, the command interneuron responsible for generating backward motion and, hence, avoidance. The presence or absence of food modulates the basic aerotactic responses of hypoxia and hyperoxia avoidance. Modulation of hyperoxia avoidance is accomplished through the neuropeptide receptor NPR-1, the transforming growth factor-\u00ce\u00b2 (TGF-\u00ce\u00b2)-related protein DAF-7, and serotonin production by the ADF neurons, whereas hypoxia avoidance seems to be mediated through a neuronal network that is independent of these pathways (Chang et al., 2006).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2981, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4df79a1f-404e-4d22-b8ab-c40fd7c161cf": {"__data__": {"id_": "4df79a1f-404e-4d22-b8ab-c40fd7c161cf", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "396840c0-71a7-4877-af56-a0f29597df37", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.4) Sensory Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "c218523a11f0ee633d6640e92b19395974512994ed2784b43c3429823984bb1d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In the wild, C. elegans inhabits rotting material which contains a broad range of CO2 levels, however as in other animals, high CO2 levels are toxic causing deterioration of muscle organization, reducing fertility and slowing development above 9% (Bretscher et al., 2008; Hallem and Sternberg, 2008; Sharabi et al, 2009). Thus, the animal typically shows an acute avoidance response to CO2 (especially well-fed animals) when CO2 level is above 0.5%. Animals also respond to changes in ambient CO2 levels. Primary CO2 sensors are AFD, BAG and ASE neurons (Bretscher et al., 2011). The signal pathway for CO2 response in AFD and BAG include the TAX-2/TAX-4 cGMP-gated heteromeric channel and the atypical soluble guanylate cyclases that also mediate oxygen responses in BAG. AFD neurons respond to increasing CO2 by a fall and then rise in Ca2+  and show a Ca2+ spike when CO2 decreases. BAG and ASE are both activated by CO2 and remain tonically active while high CO2 persists. The CO2 responses in AFD, BAG and ASE neurons do not habituate upon multiple exposures to CO2. The modulators of the CO2 -response include physiological state of the worm, the neuropeptide Y receptor, NPR-1, and calcineurin subunits, TAX-6 and CNB-1.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1227, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2e675ed9-44ce-4513-ba1a-f01c71098272": {"__data__": {"id_": "2e675ed9-44ce-4513-ba1a-f01c71098272", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.8) Process Bundles](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "36788d97-2b2d-497f-a074-1995f81ffc7b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.8) Process Bundles](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "aefa60c2ea2d6f0b758f64331aba2dff47cabd38326ec8f0571b9b67a2007be8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Most neuron processes fasciculate into organized bundles (nerves or nerve cords) that may comprise as few as two or as many as 50 processes and run in parallel over long distances within the body (NeuroFIG 7 and NeuroFIG 8). Most of these processes run longitudinally along the body wall, except where they enter the NR. Most nerve cords are specialized to include limited functional groupings. For instance, the amphid nerves in the head and the phasmid nerves in the tail include only sensory dendrites and travel directly from sensory endings to related neuron cell bodies in local ganglia. Conversely, many neuron processes of the VNC, DC, and NR have mixed functions. The number and spatial arrangement of processes within the nerve tracts are essentially conserved between animals (White et al., 1976, 1983, 1986; Chalfie and White, 1988). Neighboring processes generally stay closely associated for long distances, and synapses are made en passant between adjacent processes. The neighborhoods, therefore, determine connectivity between neurons. Switching between neighborhoods, which most commonly occurs at the junctions of process bundles, increases the number of potential synaptic partners for a given neuron. The VNC is the major longitudinal nerve and splits posteriorly to the excretory pore into major (right side) and minor (left side) tracts that flank the ventral hypodermal ridge (NeuroFIG 5). In adult animals, the left VNC tract contains six processes and the right approximately 54 processes due to the decussation of the majority of fibers exiting the NR from the left side (Hedgecock et al., 1990). Near the junction of the NR, anterior to the decussation, the ventral ganglion region contains 170 processes. The VNC is continuous with the RVG at the anterior and with the PAG at the posterior end. Many of the tail neuron processes enter the right tract of the VNC, although a few enter the left tract.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1928, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6d3b37e6-ee0f-475c-a4ee-a35d289ad8fb": {"__data__": {"id_": "6d3b37e6-ee0f-475c-a4ee-a35d289ad8fb", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.8) Process Bundles](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "87a937ff-a603-4a74-aeaf-31c50514889e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.8) Process Bundles](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "ab6faf6959978baf0dec7e94a21250b96db676965360f6621fd2ce870397423c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In the VNC, motor neuron processes may navigate between different neighborhoods to accommodate input from interneurons within the fascicle as well as their output to muscle arms positioned outside of the cord. This switch in neighborhood generally occurs at the transition between the presynaptic and post-synaptic regions of each motor neuron. The second largest nerve in the nematode, the DC, is a single tract localized on the left side of the dorsal hypodermal ridge and mainly consists of commissural processes from the VNC motor neurons joined by the processes of a small set of neurons in the head (RMED, RID) and tail (PDA, PDB).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 637, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f56e7879-06e2-4968-bdca-b91e5c50b66f": {"__data__": {"id_": "f56e7879-06e2-4968-bdca-b91e5c50b66f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.9) Commissures](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6ac971a9-10f5-43ef-a7a2-42eb49d5ef8c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.9) Commissures](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "905b6730e134580512332c18171414fe14b9bf2d96110bbecdf95643b6d3cd1f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Commissures are circumferential tracts that are created by neuron processes passing from one longitudinal nerve to another through  dorsoventral routes. Whereas in higher animals a commissure normally consists of dozens or even thousands of processes, in the nematode a commissure can consist of a single process that pioneers its own route along the body wall. The major commissures include amphid and deirid commissures in the head and lumbar, dorsorectal, and dorsolateral commissures in the tail. There are more than 40 individual commissures along the length of the body where VNC motor neuron processes extend to reach the dorsal side (NeuroFIG 7). The NR, which comprises the largest and most complex region of neuropil in the animal, is essentially an enlarged commissural region encircling the pharyngeal isthmus, with some 200 processes involved, most running a half-circle around the ring. Inside the pharynx, two shorter commissures, the pharyngeal nerve ring and the terminal bulb commissure, connect dorsal and sub-ventral pharyngeal nerve cords (see Alimentary System - Pharynx).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1094, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "951b7cbc-5a97-4292-bbc9-f89cecb19f4e": {"__data__": {"id_": "951b7cbc-5a97-4292-bbc9-f89cecb19f4e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.9) Commissures](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "dbe9a6cb-73d3-42fb-8674-077d7d92a88d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.9) Commissures](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "ce3d74edfe33072840438b3fbc998589a7dd183038f907c5da832a4d9d8e750a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Topologically, the commissures follow two types of routes: medial and lateral (NeuroFIG 12) (White et al., 1986; Durbin, 1987). The fibers in the NR follow a medially positioned route between the basal face of the hypodermis and the central muscle arm plate. During development, pioneer axons for the NR are postulated to grow inwardly along extensions of the hypodermis or along the muscle arms of the head muscles, which themselves may be organized by the GLR scaffold cells (See GLR cells). Other commissures following such medial routes include those from the dorsorectal ganglion to the preanal ganglion in the tail (Hall, 1977; Hall and Russell, 1991) and the ventrally directed HSN processes.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 699, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d1fbe975-ed56-4d93-91cc-51db8e102861": {"__data__": {"id_": "d1fbe975-ed56-4d93-91cc-51db8e102861", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.9) Commissures](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b8866c12-b4c6-44a3-95ee-fdecae501a8b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.9) Commissures](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "d2e09084b18be325ef136fe4ff5a24d392303548da23b1fc47d7e4ad796d48cc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Laterally positioned commissural routes are much more common. In these cases, neuron processes travel singly or in groups along a closely confined space underneath the body wall muscles, always in close apposition to the thin sheet of hypodermis that covers the muscle. Again, the nerves remain separated from the muscle by the basal laminae of the muscle and hypodermis. The right-sided VNC neuron commissures reach the DC by crossing over the dorsal hypodermal ridge.\n\n2.9.1 Commissures in the Head", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 500, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e3800d71-d88f-4c27-9411-378cc9edf78e": {"__data__": {"id_": "e3800d71-d88f-4c27-9411-378cc9edf78e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.9) Commissures](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4d88748e-7c4e-4591-83c6-b1d116c20c63", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.9) Commissures](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "12049fc4c0e6ff743b86c1c570fcf2b0799fa97665e0c497718251cf7b617962", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "There are four major commissures in the head: right and left amphid commissures and right and left deirid commissures (NeuroFIG 13 and NeuroFIG 14). The amphid commissures on both sides are mainly composed of axons of the amphid neurons that extend from the neuron cell bodies toward the ventral nerve cord, passing between the ventral body wall muscle and a thin sheet of hypodermis (NeuroFIG 15 and NeuroFIG 16). They also contain processes that come from the ventral cord. Processes of two such neurons, SAAV and SABV, join the anterior ventral sublateral cords as they exit the amphid commissures.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 601, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7b5e2a72-130c-450b-adb7-a24c5c500a90": {"__data__": {"id_": "7b5e2a72-130c-450b-adb7-a24c5c500a90", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.9) Commissures](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "206cca3f-3052-41e6-b052-5c5ed7574b4f", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.9) Commissures](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "e5f35fdee7aaad1759b6c98e4b0d6cec7e09e2dd6648a2eb83e1fa35cd7d0bd3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Amphid commissures are located laterally to the junction of the pharyngeal isthmus and terminal bulb. The posterior sections of the amphid commissures are also referred to as sublateral commissures because they are composed of fibers of ventral sublateral cords. Of these, anteriorly traveling PLN processes dive through the amphid commissure to join the VC on their way to the NR, whereas posteriorly traveling SIBV, SMBV, SIAV, and SMDV processes use amphid commissures to join the ventral sublateral cords. The compositions of the right and left amphid commissures are nearly mirror images of each other. The RID process (on the left side) and the SABD process (on the right side) are the exceptions.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 703, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8605936c-fd18-42c0-b427-e869064fe90d": {"__data__": {"id_": "8605936c-fd18-42c0-b427-e869064fe90d", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.9) Commissures](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0e292924-7dad-4d3b-8e66-62a8568df81e", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.9) Commissures](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "ec85fe96519a70cb7322e9bc78149c45cbd92d7d326b8b37024c603063c32a76", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The deirid commissures run near the posterior part of the terminal bulb of the pharynx (NeuroFIG 16 and NeuroFIG 17). Originating from their neuronal cell somata on the lateral sides of the head, the processes within the deirid commissures first travel posteroventrally and then medially among the cells of the retrovesicular ganglia until they join the VC. They turn anteriorly in the VC and travel to the NR. AQR is present only on the right side.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 449, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fec8c556-65fe-4688-8d69-2c80b742daac": {"__data__": {"id_": "fec8c556-65fe-4688-8d69-2c80b742daac", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.9) Commissures](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e0106bc2-42a3-47c0-acce-955e70834b2b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.9) Commissures](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "34517f1fc91e33085fe2dbc51c85f7b402862e9afb3416dd39c8671766ff680f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "There are three pairs of commissures in the tail: right and left lumbar commissures (also called ano-lumbar commissures), right and left dorsorectal commissures (also called rectal commissures), and right and left dorsolateral commissures (NeuroFIG 8 and NeuroFIG 18). The lumbar commissures are made of processes of PQR (left side), DA8 (left side), DA9 (right side), PDB (right side), PDA (right side), PVR (right side), PHAL/R, PHBL/R, PHCL/R, PVQL/R, LUAL/R, PVCL/R, PVWL/R, and PVNL/R. The majority of fibers in the lumbar commissures travel ventroanteriorly toward the PAG after originating from the lumbar ganglia neurons. However, the processes of PDA, DA9, DA8, and PDB neurons, which are situated in the PAG, travel posterodorsally through the lumbar commissures. The PDB process then continues traveling toward the tail and makes a dorsal turn within the tail tip to reach the DC, whereas the processes of PDA, DA9, and DA8 motor neurons continue their dorsal trajectory to the DC along the dorsolateral commissures. The dorsorectal commissures contain processes from DVA (right-side), AVFR (right-side), DVB (left-side), DVC (left-side), and AVG (left-side) neurons. The three dorsorectal ganglion neurons (DVA, DVB, DVC) grow their processes ventrally toward the PAG (Hall and Russell, 1991).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1305, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5750570a-7b94-42ed-b02e-4d46969b3f05": {"__data__": {"id_": "5750570a-7b94-42ed-b02e-4d46969b3f05", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.9) Commissures](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "96d8d01f-945f-48fd-a94f-f6f7fb8b3fa8", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.9) Commissures](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "da1f01b3c131d506ecb004b2d95df17d4a7a1895ac6cea0e5897ab41cf76d299", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Of the 46 VNC motor neurons that extend processes to the dorsal side, 44 (7 DA, 7 DB, 6 DD, 13 VD, and 11 AS) send their processes via body commissures, whereas DA8 and DA9 send processes to the DC via tail commissures (NeuroFIG 7 and NeuroFIG 18). The commissural processes in the body are sandwiched between muscle and hypodermis as they travel along the lateral body wall. Most of these processes travel on the right side of the animal; however, 11 of them (DA1, DA3\u00e2\u0080\u00937, DB2, DB4, DB5, DD1, VD2) make left-sided commissures (NeuroFIG 19 and NeuroFIG 20). Many travel alone or at times, two processes can join together to travel in a single commissure. The anteriormost right (made by VD1 and SABD processes) commissure is located near the posterior end of the terminal bulb of the pharynx, whereas the left (made by DB1) is around the procorpus of the pharynx (NeuroFIG 8 and NeuroFIG 20). The posteriormost body commissure (made by AS11) is close to the preanal ganglion in the tail. Along the body, other neuron processes travel dorsally or ventrally to reach longitudinal process tracts and make shorter commissures. These include SDQ dorsal processes extending to the dorsal sublateral tract on each side; HSN, PLM, PDE, and PVD ventral processes to the VNC on each side; AVM ventral process to the VNC on the right side; and PVM ventral process to the VNC on the left side.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1382, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "571cff69-0e5a-4ca2-9684-2ba577c2c310": {"__data__": {"id_": "571cff69-0e5a-4ca2-9684-2ba577c2c310", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.10) Synapses](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "dc6f417c-dbbf-49ed-b1a6-212500d7d686", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.10) Synapses](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "cf7d676b51480391f7877d5499e98b409aea1b4ce17013ff79c711816c70455a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The most important concentrations of synapses (also referred to as neuropils) are the NR, VNC, and DC. The tail has an additional region of specialized neuropil in the preanal ganglion that is substantially enlarged in the adult male tail. Very sparse chemical synapses are also found along the sublateral nerve cords, but practically none are found  in the other longitudinal nerves, including the amphid, phasmid, or the lateral nerves. Synapses involving commissural axons are apparently rare except for those locations in which a commissure crosses in close proximity to a longitudinal nerve. In general, the ganglia consist entirely of cell bodies and have no synapses. However, the lumbar and dorsorectal ganglia of the male tail also include small regions of neuropil. Occasional chemical synapses may also include alternate cell types as apparent post-synaptic partners, including hypodermal fingers in the nerve cords, marginal (epithelial) cells in the pharynx, the excretory gland, and some sex-specific epithelial cells. \n\n2.10.1 Chemical Synapses", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1059, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "033fe5d2-6e73-4d5e-b13b-ccd08ad62a1b": {"__data__": {"id_": "033fe5d2-6e73-4d5e-b13b-ccd08ad62a1b", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.10) Synapses](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "af1f198f-a4e5-4eb1-9df2-2fc7795360f3", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.10) Synapses](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "81d5762cad58bffac241fc0d8f0f49bd63c3921b32f3b6e378bde9f051d2822b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In C. elegans, chemical synapses may occur between one presynaptic and one post-synaptic cell (a monad) or more than one post-synaptic partner (a polyad; two recipients make it a dyad and three recipients make it a triad), and one may be muscle (NeuroFIG 21). Chemical synapses are made en passant between neighboring processes where synaptic swellings are formed along the process shafts. These synapses are distinguished by the presence of a small (~50 nm wide and 100\u00e2\u0080\u0093400 nm long), electron-dense presynaptic density on the cytoplasmic side of the membrane. A small cluster of synaptic vesicles lies near this density both docked and in reserve pools that comprise the \u00e2\u0080\u009cactive zone\u00e2\u0080\u009d (Weimer and Jorgensen, 2003; Rostaing et al., 2004; Zhen and Jin, 2004; Nakata et al., 2005). Further away from the active zone is a periactive zone, where molecules that coordinate synaptic organization and growth are localized and vesicle membrane may be recovered by endocytosis (Jin, 2002; Rostaing et al., 2004; Nakata et al., 2005). The size of the presynaptic region varies considerably even within the same neuron or among synapses of the same type of neuron (Jin, 2005).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1171, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "abd54d70-1b61-4181-a446-a103cf159865": {"__data__": {"id_": "abd54d70-1b61-4181-a446-a103cf159865", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.10) Synapses](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ba27a390-0ea3-4340-b979-86564b5e2984", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.10) Synapses](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "d9b8121f7056e9743506cc6a60e200c3807f4201df590d4b2fea1886011123e3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Unlike vertebrates, little or no specialization is evident by standard TEM on post-synaptic membranes in C. elegans, and, therefore, proximity determines synaptic partners. Immunochemical staining has recently confirmed that post-synaptic receptors are clustered on the post-synaptic processes, very close to the presynaptic release zone, and improved fixation methods show the presence of small post-synaptic densities (NeuroFIG 21) (Gally et al., 2004; Jin, 2005; J.-L. Bessereau and R. Weimer, pers. comm.). Recent physiological studies of neuromuscular junctions in C. elegans support the observation that a single neuron can elicit responses in multiple post-synaptic elements (Liu et al., 2006). The synaptic cleft generally appears unspecialized in the nematode.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 769, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8b45fb13-814c-4c5b-965f-fe87ff83f36b": {"__data__": {"id_": "8b45fb13-814c-4c5b-965f-fe87ff83f36b", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.10) Synapses](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0aaf3afd-42b2-4c90-94cf-7bf4f9d71216", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.10) Synapses](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "0fe81e43c2140a8b0826ae5aab376c52bcc41b477bf3e4d92f8e5f36c6bbe11a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "As in other organisms, rapid neurotransmission in C. elegans uses classical neurotransmitters, including various monoamines, acetylcholine, GABA, and glutamate. The synaptic vesicles (SV) for classical neurotransmitters that are present at the release zone tend to be small and spherical (30\u00e2\u0080\u009345 nm in diameter) and have clear contents. The absolute number of nearby vesicles ranges from 10 to 100 in the readily releasable pool. Docked vesicles are closely tethered to the presynaptic membrane within 75 nm of the presynaptic density. Cytoplasmic dense material often surrounds some or all of these vesicles, making the release zone darker than the nearby axoplasm. Vesicles are initially formed in the cell body and may lie in small clusters in the soma cytoplasm before being actively transported down the axon (Hall and Hedgecock, 1991). These transport vesicles are larger in diameter (50 nm) and more electron-dense in contents than the vesicles clustered at the release zone. While traveling along the axon as the cargo of MT-based motors, transport vesicles lie in close proximity to the MT bundle of the nerve process (Hall and Hedgecock, 1991; Zhou et al., 2001).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1174, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "bc6800dc-bf70-40d6-bb2a-680a9f16d288": {"__data__": {"id_": "bc6800dc-bf70-40d6-bb2a-680a9f16d288", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.10) Synapses](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c30c2663-b8c6-4916-b4b0-57354b07f141", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.10) Synapses](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "63a1213116bf39589a2c622fa6055aac901a06abe9202867c7c2ed99ea3b5739", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In contrast to SVs, which are clustered near the release sites, large dense-core vesicles (LDCV; 40\u00e2\u0080\u009350 nm) that contain proneuropeptides and copackaged proprotein-processing enzymes are seen throughout the presynaptic compartment (NeuroFIG 21D) (Jacob and Kaplan, 2003). C. elegans contains more than 150 putative neuropeptides that are thought to modulate synaptic function but can also mediate rapid neurotransmission via gated ion channels (Richmond and Broadie, 2002). A large fraction of C. elegans neurons use peptide neurotransmitters, and a range of behavioral defects are observed in mutants lacking these enzymes. The molecular mechanisms used for transport and membrane fusion of LDCV share some components, such as UNC-104, with those used in rapid synaptic vesicle neurotransmission.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 798, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "188cfbd8-6d3b-41b4-b4dc-dac3b6072f52": {"__data__": {"id_": "188cfbd8-6d3b-41b4-b4dc-dac3b6072f52", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.10) Synapses](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "aa97e08e-ba8a-40e4-8eea-7bc4be1b7307", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.10) Synapses](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "044c13dc751513504fbbee2a376fcc689b758b03d144826769f826512867ddce", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Small clusters of free ribosomes have been seen at both presynaptic swellings and in post-synaptic processes (Rolls et al., 2002). These ribosomes may permit local translation of messages in distal neurites. \n\n2.10.2 Neuromuscular Junctions", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 240, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "776926f5-3fcc-4f75-aecf-75800362595d": {"__data__": {"id_": "776926f5-3fcc-4f75-aecf-75800362595d", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.10) Synapses](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7b96ad7f-6b84-47c9-b1e6-e76da0300eb8", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.10) Synapses](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "ba619e397cdd15af35978e87872e282f6ef78729cb7696f05336f031361c1404", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Neuronal input to muscles occurs at specialized chemical synapses called NMJs (NeuroFIG 2D and NeuroFIG 21; also see Muscle system - Introduction). The anatomical features of these synapses are essentially the same as those for chemical synapses between neurons; however, one distinction is the basal lamina that separates the presynaptic motor neuron and the postsynaptic muscle. Basal-lamina-associated proteins nidogen/entactin (NID-1) and type XVIII (CLE-1) collagen are enriched near synaptic contacts. Nidogen is concentrated between the nerve cords and muscles, whereas CLE-1 is concentrated above the regions in which NMJs form (Ackley et al., 2003). Mutations in these basal lamina proteins lead to defects in the organization of NMJs. In contrast to most other organisms, muscles extend long, thin processes (arms) to nerve bundles to make synapses with the motor neurons in C. elegans. In many cases, chemical synapses onto muscle arms occur in specialized zones where several muscles extend arms that interdigitate to form a \u00e2\u0080\u009cmuscle plate\u00e2\u0080\u009d around a presynaptic specialization so that vesicle release from a single axon can simultaneously stimulate more than one muscle (White et al., 1976, 1986; Liu et al., 2006). In addition, there are often gap junctions between these muscle arms. For example, along the VNC and DC, muscle arms crowd around the presynaptic varicosities of the motor neurons to receive simultaneous input. Besides the VNC and DC, NMJs are also concentrated on the inside surface of the NR where muscle arms from head muscle rows arrange into a circumferential muscle plate. Unlike somatic muscles, pharyngeal muscles do not form arms, and presynaptic processes are often embedded directly in the muscle soma. In the male tail, presynaptic motor axons often terminate at the synapse, and again, contact is sometimes made directly onto the muscle soma for certain sex muscles.\n\n2.10.3 Electrical Synapses (see also chapter on Gap Junctions)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1974, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7a836ace-1ad6-4656-93f4-f91eee98028c": {"__data__": {"id_": "7a836ace-1ad6-4656-93f4-f91eee98028c", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.10) Synapses](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c7c614ea-0b7e-4ec2-98c2-457901d5969f", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.10) Synapses](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "4c5cf520083403f2a3eb90b3fb40d12a7faffd672dbff04c574303fa2de41c43", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Electrical synapses, or gap junctions (GJs), form by close contact between cells. They are found virtually in all tissues of C. elegans, and essential for embryogenesis (Phelan 2005). In the nervous system, gap junctions are made between neurons and between muscle cells (but not between neurons and muscle cells as they are generally separated by a basal lamina.) The adult C. elegans nervous system has about 600 highly reproducible neuronal gap junctions, in addition to the 5000 predicted chemical synapses (White et al., 1986). The number of gap junctions throughout the life cycle of the animal is likely much higher as some neuronal gap junctions are assembled during embryonic development but are remodeled in early larval stages and dissolved by the adult stage (Chuang et al., 2007). Between neurons, axon-to-axon and axosomatic contacts are common; soma-to-soma contacts are less common. Electrical synapses can occur at any locale within the nervous system; they are not restricted to any neuropil. These synapses may affect behavioral events by synchronizing neuronal activity, by cross-inhibition of neighboring axons, or by relaying signals along neighboring segmental regions from one homolog to another. Alternately, the gap junction may transmit metabolic signals. Some GJs have a developmental role in halting axon outgrowth when two homologous axons establish the limits of their neighboring territories, an event known as contact termination (White et al., 1986). These GJs between homologs are very common; many bilateral neuron pairs in the head encircle only half of the NR (cf. ASH, ASI, ASJ, etc.), because they stop when they encounter the process of their functional homolog to form a GJ. This property is also seen in VD motor neurons along the VNC. Important synaptic connections in the VNC can involve GJs between a command interneuron (AVA or AVB) and the cell body of a motor neuron (White et al., 1976, 1986). Other functions for gap junctions include regulation of asymmetric gene expression in a neuron pair and synchronization of neuron and muscle activities (e.g., synchronization of action potentials and Ca++ transients in body-wall muscle, Ca++ wave propogation during defecation motor program, facilitation of intermuscular electrical coupling for synchronous pharyngeal muscle contractions, transmission of signals among male-specific muscles during male copulation) (Liu et al, 2011a; Liu et al., 2011b; Chuang et al., 2007; Peters et al., 2007, Li et al, 2003). During embryogenesis transient gap junction networks may regulate formation of nascent circuits (Chuang et al., 2007).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2625, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "076f9b31-1fb8-4ddd-819d-5fc34e6fdbbe": {"__data__": {"id_": "076f9b31-1fb8-4ddd-819d-5fc34e6fdbbe", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.10) Synapses](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3082673d-ded1-4631-a2d2-d6aeba08f790", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 2.10) Synapses](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "454fa0e53b9704c2021944badca0ab818a2f11682b1d925d0b899bbfe46248b4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "GJs in nematodes are formed by intramembrane proteins called \u00e2\u0080\u009cinnexins,\u00e2\u0080\u009d which are completely different in their amino acid sequence from the vertebrate \u00e2\u0080\u009cconnexins.\u00e2\u0080\u009d Instead, they are the homologs of vertebrate \"pannexins\" (Starich et al., 1996; Phelan and Starich, 2001; Altun et al., 2009). They may coassemble to form homotypic, heterotypic and heteromeric gap junctions (NeuroFIG 22). Additionally, these molecules may form hemichannels that connect a cell\u00e2\u0080\u0099s interior to the extracellular space, providing a pathway for release and uptake of molecules and ions in a controlled manner. In addition to eat-5 , unc-7 , and unc-9 , which had been discovered previously through mutant analyses, the completion of genomic sequencing of C. elegans revealed 22 more innexin genes (C. elegans Sequencing Consortium, 1998; Bargmann, 1998). These additional innexins were numbered arbitrarily from inx-1to inx-22. Further sequencing and genomic analysis of two additional Caenorhabditis species (C. briggsae and C. remanei) revealed that each of these species has retained at least one member of each type of these innexins, except inx-8 and , which share a single ortholog in C. briggsae, but have distinct orthologs in C. remanei (see Wormbase). This strongly suggests that each innexin gene is a true gene rather than a pseudogene. Among C. elegans innexins, there are 3 sets of polycistronic ones: inx-12 and inx-13 , inx-16 and inx-17 , and inx-21 , and inx-22. Individual GJs in neurons can involve heteromeric channels made from several different innexin subunits. Neuronal GJs differ from those in other nematode tissues by showing equal numbers of intramembrane particles in both the \u00e2\u0080\u009cE-face\u00e2\u0080\u009d and \u00e2\u0080\u009cP-face\u00e2\u0080\u009d (Hall, 1987). Through expression analyses all innexins except inx-5 , inx-15 , inx-16 , inx-20 , inx-21 , inx-22 , and eat-5 were found in the C. elegans nervous system (Altun et al., 2009). Among these, the most widely expressed innexins were inx-7 , unc-7 , and unc-9, while the least widely expressed ones were inx-1 , inx-2 , and inx-11. Also, TEM analyses revListealed that gap junctions exist between glia (socket and sheath cells) and hypodermis as well as between the socket and sheath cells, but not between glia and neurons (Altun et al., 2009).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2281, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ebd4ed9f-0841-4155-8b69-9418ab65397e": {"__data__": {"id_": "ebd4ed9f-0841-4155-8b69-9418ab65397e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 3) List of Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "61ca1a6e-86d4-444e-b90a-c7394b252475", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 3) List of Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "5a5b94c67932cc6901905eabcc39d0150172f080ba3fc7f687dfb39de0464a35", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Individual neurons", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 18, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "06a6da42-d435-41eb-ab31-47e09712bfe7": {"__data__": {"id_": "06a6da42-d435-41eb-ab31-47e09712bfe7", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 3) List of Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f60948f8-fd1e-4c6d-bb9a-b0e00c2bd212", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 3) List of Neurons](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "4e0f8cc3d57fbd91f516db43a9dacaf0340162179730f85d9691de2289b21b4f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Use drop down menus to go to individual neuron pages. \n\n  Select Cell A  ADAL  ADAR  ADEL  ADER  ADFL  ADFR  ADLL  ADLR  AFDL  AFDR  AIAL  AIAR  AIBL  AIBR  AIML  AIMR  AINL  AINR  AIYL  AIYR  AIZL  AIZR  ALA  ALML  ALMR  ALNL  ALNR  AQR  AS1  AS2  AS3  AS4  AS5  AS6  AS7  AS8  AS9  AS10  AS11  ASEL  ASER  ASGL  ASGR  ASHL  ASHR  ASIL  ASIR  ASJL  ASJR  ASKL  ASKR  AUAL  AUAR  AVAL  AVAR  AVBL  AVBR  AVDL  AVDR  AVEL  AVER  AVFL  AVFR  AVG  AVHL  AVHR  AVJL  AVJR  AVKL  AVKR  AVL  AVM  AWAL  AWAR  AWBL  AWBR  AWCL  AWCR   \n\n   Select Cell B-H  BAGL  BAGR  BDUL  BDUR  CA1  CA2  CA3  CA4  CA5  CA6  CA7  CA8  CA9  CANL  CANR  CEMDL  CEMDR  CEMVL  CEMVR  CEPDL  CEPDR  CEPVL  CEPVR  CP0  CP1  CP2  CP3  CP4  CP5  CP6  CP7  CP8  CP9  DA1  DA2  DA3  DA4  DA5  DA6  DA7  DA8  DA9  DB1/3  DB2  DB3/1  DB4  DB5  DB6  DB7  DD1  DD2  DD3  DD4  DD5  DD6  DVA  DVB  DVC  DVE  DVF  DX1/2  DX3/4  EF1/2  EF3/4  FLPL  FLPR  HOA  HOB  HSNL  HSNR   \n\n   Select Cell I-O  I1L  I1R  I2L  I2R  I3  I4  I5  I6  IL1DL  IL1DR  IL1L  IL1R  IL1VL  IL1VR  IL2DL  IL2DR  IL2L  IL2R  IL2VL  IL2VR  LUAL  LUAR  M1  M2L  M2R  M3L  M3R  M4  M5  MCL  MCR  MI  NSML  NSMR  OLLL  OLLR  OLQDL  OLQDR  OLQVL  OLQVR   \n\n   Select Cell P  PCAL  PCAR  PCBL  PCBR  PCCL  PCCR  PDA  PDB  PDC  PDEL  PDER  PGA  PHAL  PHAR  PHBL  PHBR  PHCL  PHCR  PLML  PLMR  PLNL  PLNR  PQR  PVCL  PVCR  PVDL  PVDR  PVM  PVNL  PVNR  PVPL  PVPR  PVQL  PVQR  PVR  PVS  PVT  PVU  PVV  PVWL  PVWR  PVY  PVX  PVZ   \n\n   Select Cell R  R1AL  R1AR  R1BL  R1BR  R2AL  R2AR  R2BL  R2BR  R3AL  R3AR  R3BL  R3BR  R4AL  R4AR  R4BL  R4BR  R5AL  R5AR  R5BL  R5BR  R6AL  R6AR  R6BL  R6BR  R7AL  R7AR  R7BL  R7BR  R8AL  R8AR  R8BL  R8BR  R9AL  R9AR  R9BL  R9BR  RIAL  RIAR  RIBL  RIBR  RICL  RICR  RID  RIFL  RIFR  RIGL  RIGR  RIH  RIML  RIMR  RIPL  RIPR  RIR  RIS  RIVL  RIVR  RMDDL  RMDDR  RMDL  RMDR  RMDVL  RMDVR  RMED  RMEL  RMER  RMEV  RMFL  RMFR  RMGL  RMGR  RMHL  RMHR   \n\n   Select Cell S-V  SAADL  SAADR  SAAVL  SAAVR  SABD  SABVL  SABVR  SDQL  SDQR  SIADL  SIADR  SIAVL  SIAVR  SIBDL  SIBDR  SIBVL  SIBVR  SMBDL  SMBDR  SMBVL  SMBVR  SMDDL  SMDDR  SMDVL  SMDVR  SPCL  SPCR  SPDL  SPDR  SPVL  SPVR  URADL  URADR  URAVL  URAVR  URBL  URBR  URXL  URXR  URYDL  URYDR  URYVL  URYVR  VA1  VA2  VA3  VA4  VA5  VA6  VA7  VA8  VA9  VA10  VA11  VA12  VB1  VB2  VB3  VB4  VB5  VB6  VB7  VB8  VB9  VB10  VB11  VC1  VC2  VC3  VC4  VC5  VC6  VD1  VD2  VD3  VD4  VD5  VD6  VD7  VD8  VD9  VD10  VD11  VD12  VD13", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2439, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2c96c420-c4c0-4928-a795-d9b8a0642fed": {"__data__": {"id_": "2c96c420-c4c0-4928-a795-d9b8a0642fed", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 4) References](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7037cb74-9069-494d-a079-835c249727a5", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 4) References](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "46e73bcc948b8fe62018cc8cb321fc7cd41ad01b0f34291f082208d34ce26b98", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Bargmann, C.I., Hartwieg, E. and Horvitz, H.R. 1993. Odorant-selective genes and neurons mediate olfaction in C. elegans. Cell 74: 515\u00e2\u0080\u0093 27. Abstract", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 150, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1298c074-e7ca-43d7-92fb-6aafdce72c4d": {"__data__": {"id_": "1298c074-e7ca-43d7-92fb-6aafdce72c4d", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 4) References](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "94adfa80-2dd1-4617-8774-eed4dbc296cc", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Nervous System, Section 4) References](https://www.wormatlas.org/hermaphrodite/nervous/Neuroframeset.html)"}, "hash": "07b7f07b693e6675df1f1d3732e4f309170edfda9bc37a6490aa94f3492deb08", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Troemel, E.R., Kimmel, B.E., Bargmann, C.I. 1997. Reprogramming chemotaxis responses: sensory neurons define olfactory preferences in C. elegans. Cell 91: 161\u00e2\u0080\u0093169. Article", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 173, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "02bf347d-a130-4c21-813c-435120f0efe7": {"__data__": {"id_": "02bf347d-a130-4c21-813c-435120f0efe7", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Reproductive System, Section 1) General Description](https://www.wormatlas.org/hermaphrodite/reproductive/Reproframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b58d8fde-8aa7-4d9b-887d-9d857fb8e0bc", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Reproductive System, Section 1) General Description](https://www.wormatlas.org/hermaphrodite/reproductive/Reproframeset.html)"}, "hash": "b3dc1958930c32c61c069a09501cd4fd932337da13ba8ee0368bd761675f45fc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The reproductive system is one of the most sexually dimorphic tissues in the animal, with many components differing between hermaphrodites and males (see Introduction for an overview of the male anatomy). The hermaphrodite reproductive system produces mature gametes and provides the structure and environment for fertilization and egg-laying (ReproFIG 1). It can be divided into three major parts: the somatic gonad (described in Reproduction System - Somatic Gonad), the germ line (Reproductive System - Germ Line), and the egg-laying apparatus (Reproductive System - Egg-laying Apparatus) (ReproTABLE 1). The somatic gonad and germ line together form two symmetrical U-shaped tubes (arms) that are joined to a common uterus and egg-laying apparatus in the midbody.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 767, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cb8b57f9-f36e-4e0b-9077-c4ee440e4b7b": {"__data__": {"id_": "cb8b57f9-f36e-4e0b-9077-c4ee440e4b7b", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Reproductive System, Section 1) General Description](https://www.wormatlas.org/hermaphrodite/reproductive/Reproframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3b835c89-2e4b-425c-9dd4-84b096040d0a", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Reproductive System, Section 1) General Description](https://www.wormatlas.org/hermaphrodite/reproductive/Reproframeset.html)"}, "hash": "65617325ba2e6e25e01c3b672ad2f3dbb5c195629ee87268a65afafd07185454", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The somatic gonad is composed of the distal tip cell (DTC), gonadal sheath, spermatheca (sp), spermathecal-uterine (sp-ut) valve, and uterus (the uterus can also be considered part of the egg-laying apparatus). The adult germ line is organized in a distal-to-proximal manner, with distal corresponding to the region approaching the distal tip cell, and proximal corresponding to the nearest point at which embryos exit from the animal. Germ cells in the distal-most part of the gonad arm are mitotic and undifferentiated. As germ cells move proximally, they enter and pass through the stages of meiosis I prophase, reaching pachytene in the loop region, then progress further through meiosis in the proximal arm (ReproFIG 1). The egg-laying apparatus consists of the vulva, uterine and vulval muscles, left and right hermaphrodite specific neurons (HSNL/R), and VC1\u00e2\u0080\u00936 neurons. The hermaphrodite is considered a specialized self-fertile female because the soma is female but the germ line first produces a fixed number of male gametes (sperm) before switching to the sole production of female gametes (oocytes) (L\u00e2\u0080\u0099Hernault, 1997; Schedl,1997).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1146, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a0ea0a00-d273-4657-b6dd-7ec3503ec1ad": {"__data__": {"id_": "a0ea0a00-d273-4657-b6dd-7ec3503ec1ad", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Reproductive System, Section 1) General Description](https://www.wormatlas.org/hermaphrodite/reproductive/Reproframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "212edce7-ff9a-45ff-9537-63d7b6a5eb47", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Reproductive System, Section 1) General Description](https://www.wormatlas.org/hermaphrodite/reproductive/Reproframeset.html)"}, "hash": "535258fcd36556a38adfc8af4c34f05c67a78f539f245777bcbabd9db4cc6fdf", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Hermaphrodites produce approximately 300 embryos by fertilization of oocytes with self-sperm (the process of self-fertilization). Fertilization is also achieved using male-derived sperm, transferred during copulation. In the proximal gonad, oocytes undergo maturation and are ovulated in single-file, assembly-line fashion into the sperm-containing spermatheca where they are fertilized (Singson, 2001). Fertilized eggs then move into the uterus. Activity of the egg-laying apparatus subsequently forces eggs out into the environment by passing them through a ventral opening called the vulva.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 593, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "42618383-fc76-46b2-8e15-0aa7798dabe6": {"__data__": {"id_": "42618383-fc76-46b2-8e15-0aa7798dabe6", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Reproductive System, Section 2) Lineal Origin of the Reproductive System](https://www.wormatlas.org/hermaphrodite/reproductive/Reproframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1ebaa647-6619-4f72-906c-3cab82f2a7dd", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Reproductive System, Section 2) Lineal Origin of the Reproductive System](https://www.wormatlas.org/hermaphrodite/reproductive/Reproframeset.html)"}, "hash": "b70e63c893fd4f36bf79507d8bb84655d95c9598f0b210cc7042ec3c5f7b085c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Formation of the reproductive system spans the entire post-embryonic period. The reproductive system is formed by cells from several lineages (ReproTABLE 1; ReproFIG 2), including some that originate more posteriorly and must migrate considerable distances to be included in the developing system (e.g., the HSNs and uterine and vulval muscle precursors) (Sulston and Horvitz, 1977; Sulston et al., 1983). Not surprisingly, the organization of this complex system involves a hierarchy of temporally and spatially coordinated signaling events and cell\u00e2\u0080\u0093cell interactions (Sulston and White, 1980; Kimble, 1981; Sternberg and Horvitz, 1986; Sternberg, 1988; Thomas et al., 1990). The developing gonad itself serves as the primary organizer, promoting development of the vulva and uterus and guiding the precise positioning of sex muscle precursors (Kimble, 1981; Sternberg and Horvitz, 1986; Thomas et al., 1990; Newman et al., 1995). The vulva, in turn, acts as a secondary organizer for assembly of the egg-laying apparatus (Li and Chalfie, 1990; Thomas et al., 1990; Garriga et al., 1993; Chang et al., 1999; Shen and Bargmann, 2003; Shen et al., 2004). Finally, within the gonad itself, interactions between somatic tissues and the germ line have a critical role in promoting germ-line proliferation, polarity, progression of meiosis, ovulation, and gamete sexual identity (Kimble and White, 1981; Seydoux et al., 1990; McCarter et al., 1997; Pepper et al., 2003; Killian and Hubbard, 2004).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1494, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3dbb4f71-7898-4781-acac-a03e02f14425": {"__data__": {"id_": "3dbb4f71-7898-4781-acac-a03e02f14425", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Reproductive System, Section 2) Lineal Origin of the Reproductive System](https://www.wormatlas.org/hermaphrodite/reproductive/Reproframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "109da128-c8ab-464a-807f-37e750d423de", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Reproductive System, Section 2) Lineal Origin of the Reproductive System](https://www.wormatlas.org/hermaphrodite/reproductive/Reproframeset.html)"}, "hash": "21eafd2f56112e69cb8a16dfcb1ed5777d022e0e62a56a0e916854638808262c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Some maturation events occur remarkably late in reproductive system development. For instance, several anatomical changes are associated with ovulation. Spermatids, generated within the gonadal sheath, are pushed into the spermatheca by passage of the first oocyte. There they mature into spermatozoa (sperm) (L\u00e2\u0080\u0099Hernault ,1997). The sp-ut valve and uterus also undergo structural modification as a consequence of this first ovulation (J. White, unpubl.; D.H. Hall, unpubl.).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 476, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "722cf704-9e1f-4b61-8c82-b988fa15406a": {"__data__": {"id_": "722cf704-9e1f-4b61-8c82-b988fa15406a", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Reproductive System, Section 3) References](https://www.wormatlas.org/hermaphrodite/reproductive/Reproframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3773a2a4-6647-4722-b427-683d2661b56d", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Reproductive System, Section 3) References](https://www.wormatlas.org/hermaphrodite/reproductive/Reproframeset.html)"}, "hash": "8cd947f309732be43dd06c02f44abb2892b7b4daea7de03ecc7bc0459849e90f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Chang, C., Newman, A.P. and Sternberg, P.W. 1999. Reciprocal EGF signaling back to the uterus from the induced C. elegans vulva coordinates morphogenesis of epithelia. Curr. Biol. 9: 237-246. Article", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 199, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "295adf07-2aec-4863-8153-a74c6a85e8cd": {"__data__": {"id_": "295adf07-2aec-4863-8153-a74c6a85e8cd", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Reproductive System, Section 3) References](https://www.wormatlas.org/hermaphrodite/reproductive/Reproframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ba9b04dc-048f-4ab2-bdbe-1b9e35d8e8ac", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Reproductive System, Section 3) References](https://www.wormatlas.org/hermaphrodite/reproductive/Reproframeset.html)"}, "hash": "7e2bee9a673f07c1a6193cdb612850ffe9a7191cef8a318d9a94e6956505f075", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Garriga, G., Desai, C. and Horvitz, H.R. 1993. Cell interactions control the direction of outgrowth, branching and fasciculation of the HSN axons of Caenorhabditis elegans. Development 117: 1071-1087. Article", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 208, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8faba000-f022-484c-aa3e-1226d0e4ca34": {"__data__": {"id_": "8faba000-f022-484c-aa3e-1226d0e4ca34", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Coelomocyte System, Section 1) General Information](https://www.wormatlas.org/hermaphrodite/coelomocyte/Coelomoframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8c27d25f-b6ae-406d-9eea-3eb19b120a17", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Coelomocyte System, Section 1) General Information](https://www.wormatlas.org/hermaphrodite/coelomocyte/Coelomoframeset.html)"}, "hash": "c32555d028f9fc1bd14388b30b4a76906c2f47fef2c3f951b673fea3e95a963a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The adult C. elegans hermaphrodite has six coelomocytes: large, ovoid, mesodermal cells situated as three pairs (right, left and dorsal) in the pseudocoelomic cavity adjacent to the somatic musculature (CcFIG 1). Four coelomocytes are present at hatching and two are generated in the first larval stage. Because there is evidence for absorption and concentration of soluble materials by coelomocytes of various nematode species, these cells were suggested to be phagocytic and similar in function to the macrophages of vertebrates (Chitwood and Chitwood, 1950). In larger nematode species, such as Ascaris suum, the coelomocytes can indeed phagocytose invading organisms (Bolla et al., 1972). Their inclusions and vesicles stain easily with dyes such as Methylene blue, Neutral red and Neutral violet, and these dyes sometimes appear to collect in high concentrations. Similarly, because of their ability to continuously endocytose and accumulate a variety of macromolecules from the body cavity fluid, coelomocytes of C. elegans have been suggested to serve immune, scavenging and hepatic functions (Fares and Grant, 2002; Yanowitz and Fire, 2005). Unlike macrophages of higher organisms, however, coelomocytes of C. elegans do not seem to be capable of phagocytosis (Ewbank, 2002). Also, they are not actively migratory and their position in the body cavity is relatively fixed, possibly by attachments to the body wall. As a result, coelomocytes rely on both the movements of the animal and the body cavity fluid for accessing foreign material.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1547, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c804271f-ede3-419b-ad62-e5b86cd4134e": {"__data__": {"id_": "c804271f-ede3-419b-ad62-e5b86cd4134e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Coelomocyte System, Section 1) General Information](https://www.wormatlas.org/hermaphrodite/coelomocyte/Coelomoframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "63f0f944-3296-478b-bff2-b3e7b82cdc63", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Coelomocyte System, Section 1) General Information](https://www.wormatlas.org/hermaphrodite/coelomocyte/Coelomoframeset.html)"}, "hash": "bc50db3804d8b3c7dc6fbb8ea4ad6e4d097ac3b9fa9f6b76fd6799d25325bf44", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Like the intestine and gonad, coelomocyte positioning reveals dextral handedness of the animal grown at 20\u00b0C; the ventral anterior pair is located on the right side and close to the pharynx, and the ventral posterior pair is on the left side and anterior to the vulva. When animals are cultivated at 10\u00b0C, this handedness may become reversed such that 0.5% of animals shows sinistral handedness instead of dextral (Wood et al., 1996). Of the dorsal pair of coelomocytes, one cell is located on the right side and one is located on the left.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 540, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1dfa9ed7-f3ff-43cd-8de4-2e04c8de312a": {"__data__": {"id_": "1dfa9ed7-f3ff-43cd-8de4-2e04c8de312a", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Coelomocyte System, Section 2) Embryonic Development](https://www.wormatlas.org/hermaphrodite/coelomocyte/Coelomoframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "aec06691-f015-4073-af5b-d387f72c99b7", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Coelomocyte System, Section 2) Embryonic Development](https://www.wormatlas.org/hermaphrodite/coelomocyte/Coelomoframeset.html)"}, "hash": "9e88a84a39ff242400285e024e657a6de8ef70718f4264853290bcce5b237abb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The coelomocytes arise from embryonic MS (mesodermal blast) and postembryonic M lineages (CcFIG 2). The right ventral (ventral anterior; ccAR and ccPR) and the left ventral (ventral posterior; ccAL and ccPL) pairs are derived from MS granddaughters MSpp and MSap, respectively (CcFIG 2 and CcFIG 3). They are generated from symmetrical divisions late in embryogenesis, when most of the other embryonic cell divisions have been completed (Sulston et al., 1983). Although the mother cell for each pair is born during the large burst of embryonic cell divisions, they remain arrested for a couple of hours before final cell division and differentiation. During this arrest in cell division before the elongation of the embryo, the two mother cells migrate posteriorly from the head where there are born, giving rise to the specific localizations of their daughter pairs of coelomocytes (CcFIG 2) (Hedgecock et al., 1987).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 918, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4af69897-49d4-488c-8006-3a418d650a1c": {"__data__": {"id_": "4af69897-49d4-488c-8006-3a418d650a1c", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Coelomocyte System, Section 2) Embryonic Development](https://www.wormatlas.org/hermaphrodite/coelomocyte/Coelomoframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "78a683c6-5c81-4bf1-a5c6-f14df56974c4", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Coelomocyte System, Section 2) Embryonic Development](https://www.wormatlas.org/hermaphrodite/coelomocyte/Coelomoframeset.html)"}, "hash": "bf4ea314cb01e883675276ebaaa00820bfd2d417329037180df1ddad39d42536", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The MS lineage also gives rise to the M mesoblast, which is responsible for all nongonadal mesoderm formation during post-embryonic development, including the two dorsal coelomocytes (ccDR and ccDL). The M mesoblast is born on the left side of the embryo next to the pharynx and then migrates to the posterior of the animal, following a ventral path between the two germ-line progenitors Z2 and Z3. It lingers on the midline for some time, but eventually moves to the right-hand side of the intestine and attaches to the body wall over QV5 (CcFIG 2 and CcFIG 4) (Sulston et al., 1983). Here, several consecutive divisions give rise to 18 cells by the L1 molt. Of these cells, 14 become body wall (striated) muscles, 2 become sex (nonstriated) muscle progenitor cells, and 2 dorsal cells (Mdlpa and Mdrpa) differentiate into coelomocytes during the L2 stage. In males, the M lineage gives rise to a single dorsal coelomocyte so that the total number of coelomocytes in males is five instead of six. Also in L1 males, one of the ventral left-side coelomocytes is located posterior to the gonad primordium rather than anteriorly, as in L1 hermaphrodite (see Introduction to Male Anatomy - Anatomical differences between sexes; Sulston and Horvitz, 1977).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1251, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5e1d1aa6-cec1-4e8f-8f4c-19840141ea85": {"__data__": {"id_": "5e1d1aa6-cec1-4e8f-8f4c-19840141ea85", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Coelomocyte System, Section 3) Structure and Function](https://www.wormatlas.org/hermaphrodite/coelomocyte/Coelomoframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "313bc75a-eca7-4c26-8b07-6db1a81937e5", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Coelomocyte System, Section 3) Structure and Function](https://www.wormatlas.org/hermaphrodite/coelomocyte/Coelomoframeset.html)"}, "hash": "a684886997f252d9c7b81869d337c090020481a93fdb148fd4d34fbdeef8a3a8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "While coelomocytes in C. elegans  are ovoid in shape, they can adopt stellate shapes in some other species. Each coelomocyte is about 10-15 \u03bcm in diameter and its cytoplasm contains a distended rough endoplasmic reticulum and many membrane-bound vesicles of various sizes ( CcFIG 5 ) ( Fares and Greenwald, 2001 ). When viewed by DIC optics, the cells are distinctive in that they contain both pale vacuoles and highly refractile inclusions ( Sulston and Horvitz, 1977 ). Each cell is covered by its own basal lamina. Some portions of the plasma membrane show active endocytosis, with multiple, approximately 0.1 \u03bcm endocytic invaginations lying in close proximity to one another ( CcFIG 5 ). Foreign substances such as India ink, rhodamine-dextran, GFP, fluorescein isothiocyanate (FITC)-BSA and FITC-lipopolysaccharide of S. typhimurium, that are injected into the body cavity of C. elegans are rapidly taken up by coelomocytes ( Fares and Greenwald, 2001 , Zhang, et al., 2001 ). Although they do not normally take up yolk particles from the pseudocoelom, coelomocytes can be induced to take up GFP-tagged yolk particles, apparently due to the presence of the GFP moiety ( Paupard et al., 2001 ).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1199, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0eb13dba-191b-4df3-be9c-ed1e554656e9": {"__data__": {"id_": "0eb13dba-191b-4df3-be9c-ed1e554656e9", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Coelomocyte System, Section 3) Structure and Function](https://www.wormatlas.org/hermaphrodite/coelomocyte/Coelomoframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cedc0307-6858-4460-a6f1-25b9f0164144", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Coelomocyte System, Section 3) Structure and Function](https://www.wormatlas.org/hermaphrodite/coelomocyte/Coelomoframeset.html)"}, "hash": "c50e05a550a73638b5d95ca3d16c71ca89d48b3efefa7e28a51c3e30f032d217", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Consistent with their role in uptake, several proteins known to function in endocytosis in other organisms are active in C. elegans coelomocytes (Fares and Greenwald, 2001). The fluid-phase markers that are taken up by coelomocytes travel through the endocytic (early and late) compartments and eventually reach lysosomes where they are degraded or stored if they are not amenable to digestion (Fares and Grant, 2002; Treusch et al., 2004). This active endocytosis by coelomocytes may function for scavenging as a primitive immune surveillance function. This function does not seem to be significant or essential for the animal's survival or fertility, however, because animals tolerate changes in the number of coelomocytes. Also, when coelomocytes are toxin-ablated, the treated animals continue to grow and bear progeny (Harfe et al., 1998; Fares and Greenwald, 2001; Yanowitz and Fire, 2005). Additionally, C. elegans seems to be susceptible to the intrapseudocoelomic injection of even small amounts of bacteria, which normally do not gain access to pseudocoelom due to three barriers: The grinder of the pharynx breaks down bacteria entering from the mouth; the multilayered cuticle envelops the body, acting a physical barrier; and a complex innate immune system that, at least in part, resembles that of higher organisms may function as a defense against bacterial infection (Millet and Ewbank 2004; Nicholas and Hodgkin 2004).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1435, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5fb7161d-ed3f-4a7f-b6dc-d95d84c20a38": {"__data__": {"id_": "5fb7161d-ed3f-4a7f-b6dc-d95d84c20a38", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Coelomocyte System, Section 5) References](https://www.wormatlas.org/hermaphrodite/coelomocyte/Coelomoframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "665e0b98-3a3d-45d2-a97f-2433b4e428d2", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Coelomocyte System, Section 5) References](https://www.wormatlas.org/hermaphrodite/coelomocyte/Coelomoframeset.html)"}, "hash": "285f670d82149d0af4bfb9c29999388235a06fe627d0adcc67099da2ea14c500", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Zhang, Y., Grant, B. and Hirsh, D. 2001. RME-8, a conserved J-domain protein, is required for endocytosis in Caenorhabditis elegans. Mol. Biol. Cell 12: 2011-2021. Article", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 171, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0a74b8fe-a5bd-4da3-9598-2824b33b65da": {"__data__": {"id_": "0a74b8fe-a5bd-4da3-9598-2824b33b65da", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Muscle System Introduction, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/muscleintro/MusIntroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e6c5b86a-032b-44d8-8eee-88f4ad5b6e2c", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Muscle System Introduction, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/muscleintro/MusIntroframeset.html)"}, "hash": "4eb5d8161708c92fad86021876c1d160e8a9958b59c19ed38b9621196635315d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "There are two main types of muscle in C. elegans: multiple sarcomere/obliquely striated (somatic) and nonstriated (also called single sarcomere). The multiple sarcomere muscles contain evenly distributed attachment points to the hypodermis and cuticle along their length (see Somatic muscle), whereas the majority of the nonstriated muscles have focal attachment points at their ends. The multiple sarcomere group is the most abundant muscle group, consisting of 95 body wall muscles; 14 of these are post-embryonically generated (see Somatic muscle). The nonstriated muscle group in hermaphrodites includes 20 pharyngeal muscles, 2 stomato-intestinal muscles, 1 anal sphincter muscle, 1 anal depressor muscle, 8 vulval muscles (all post-embryonically generated), 8 uterine muscles (all post-embryonically generated) and contractile gonadal sheath (see Nonstriated Muscle). In the male, instead of the vulval and uterine muscles and gonadal sheath, 41 specialized mating muscles are present, some having single sarcomeres and some being obliquely striated. Except for the pm1-pm5 cells of the pharynx, all muscle cells are mononucleate. After hatching, pm1 becomes a syncytial cell with 6 nuclei, and pm2-pm5 become binucleate syncytial cells (see Alimentary System - Pharynx).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1277, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "00c307be-0447-4a6e-9010-92dec2619021": {"__data__": {"id_": "00c307be-0447-4a6e-9010-92dec2619021", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Muscle System Introduction, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/muscleintro/MusIntroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5f4aca97-b7fa-40c7-ab33-69f5557c814b", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Muscle System Introduction, Section 1) Overview](https://www.wormatlas.org/hermaphrodite/muscleintro/MusIntroframeset.html)"}, "hash": "c577df465e104b5d13e4f22cbcf821a3f1d36e5c7d609b82cb5c8b76aadb4445", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Although most muscle contractions are generated by nerve transmission, three rhythmic behavior cycles in C. elegans are dependent on periodical contraction of certain muscle groups with recurrent intracellular Ca++ transients rather than excitation by neuronal transmission. These are: pharyngeal pumping behavior of the pharyngeal muscle (see Alimentary system - Pharynx), gonadal sheath contractions, and the defecation cycle involving three muscle groups: body wall (somatic) muscles near the head, posterior (somatic) body wall muscles and enteric muscles (i.e., anal depressor, sphincter, and stomato-intestinal muscles) (see Alimentary system - Rectum and Anus). Although they are generated by intrinsic motor activity, pharyngeal pumping and enteric muscle contractions are modulated by neurons.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 802, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f6fc2b68-823c-4e7d-8349-88cb88c1a25f": {"__data__": {"id_": "f6fc2b68-823c-4e7d-8349-88cb88c1a25f", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Muscle System Introduction, Section 2) Structure of the Contractile Apparatus](https://www.wormatlas.org/hermaphrodite/muscleintro/MusIntroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7ec3ab2f-d0bb-4062-a5c8-345091d4acdd", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Muscle System Introduction, Section 2) Structure of the Contractile Apparatus](https://www.wormatlas.org/hermaphrodite/muscleintro/MusIntroframeset.html)"}, "hash": "b69998f9c894db4cfe0ba58c360600eeb46ebeac0bfe41512e4b658861f3d9bb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The basic unit of the contractile apparatus in muscle is the sarcomere (MusFIG1A). In striated muscle these contractile units are repeated, giving the muscle its \"striated\" appearance. In vertebrates, a sarcomere is comprised of Z (Zwischenscheibe) discs located at each end of sarcomere; I (isotropic) bands, which correspond to thin filaments; A (anisotropic) bands, which correspond to thick filaments (including the thin filament overlap region); H (Heller) bands, which correspond to the central region of the A bands and M lines at the middle of the H bands where each myosin rod is joined end-to-end with its myosin rod neighbor (MusFIG 1). In the sarcomere, myosin-containing thick filaments are interdigitated with actin-containing thin filaments on either side. In C. elegans, the Z-disc analog is the dense body (DB), which functions to anchor and align thin filaments in striated muscles (MusFIG 1B; see Somatic Muscle). Thick filaments are attached to M-line analogs. Both the DB and the M-line analogs extend the entire depth of the lattice and anchor all filaments to the cell membrane and the underlying hypodermis and cuticle (see Somatic Muscle). In nonstriated muscles with single sarcomeres, large hemiadherens junctions (formerly called hemidesmosomes) connect each sarcomere at the muscle ends to body cuticle or specialized cuticle and/or to basal lamina to anchor the myofilaments (see Nonstriated Muscle). Some of the nonstriated muscles have myofilaments that are less well organized. Here, anchorages occur via small plaques and hemiadherens junctions distributed along the cell membrane similar to the organization of vertebrate smooth muscle (MusFIG 1A&B and MusFIG 1C&D, see Nonstriated Muscle).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1725, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5107ffff-5c8e-42b7-96f8-dae31de5904e": {"__data__": {"id_": "5107ffff-5c8e-42b7-96f8-dae31de5904e", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Muscle System Introduction, Section 2) Structure of the Contractile Apparatus](https://www.wormatlas.org/hermaphrodite/muscleintro/MusIntroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "582a8826-c503-4488-91bd-212cb5496d53", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Muscle System Introduction, Section 2) Structure of the Contractile Apparatus](https://www.wormatlas.org/hermaphrodite/muscleintro/MusIntroframeset.html)"}, "hash": "5e26281e752e821d5d64804e61dd0318b64d70a102f117c7194abbdab96cf676", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The organization of the muscle filament lattice in C. elegans can be viewed by polarized light microscopy, to both assess the orientation of the filaments in wild type body muscles as they develop and to score for defects in mutant strains.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 240, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "afe805fb-272c-4b7b-aaf2-571f3ea2fe06": {"__data__": {"id_": "afe805fb-272c-4b7b-aaf2-571f3ea2fe06", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Muscle System Introduction, Section 3.1) EC Coupling in Vertebrate Muscle](https://www.wormatlas.org/hermaphrodite/muscleintro/MusIntroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f69e0e89-de7b-44de-8686-7939dee28465", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Muscle System Introduction, Section 3.1) EC Coupling in Vertebrate Muscle](https://www.wormatlas.org/hermaphrodite/muscleintro/MusIntroframeset.html)"}, "hash": "921ac8cb59ab3ba291322ebd196309ad4c7544d4f19356de7972f0374c6da86c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Excitation-contraction coupling (ECC) is the process by which an action potential triggers a muscle cell to contract. In vertebrates, myocytes respond to the excitation signal induced by their innervating motor neurons with a rapid depolarization, which is coupled with contraction of the muscle as its physiological response. The initial depolarization in the muscle caused by nerve transmission is a localized phenomenon and the depolarization signal is carried to the myofibrils deep within the cell body via sarcolemmal (cell membrane) invaginations called transverse (T) - tubules. T-tubules form a network of membranes that penetrate and span the cross section of each muscle cell, transmitting the depolarization signal uniformly throughout the muscle fiber (MusFIG 2). The lumena of the T-tubules are continuous with the extracellular fluid, and the membrane depolarization during an action potential diffuses across the T-tubule membrane. The T-tubules are close to the border between the A- and I-bands of the myofibrils and are in close apposition with cisternae formed by the Sarcoplasmic Reticulum (SR). This association is called a triad. T-tubules are essential structures for excitation-contraction coupling linking the depolarization of the action potential to Ca++ release from SR where intracellular Ca++ is sequestered (MusFIG 2B).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1351, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1432a1df-0a1a-405e-8884-cbafb20be6f5": {"__data__": {"id_": "1432a1df-0a1a-405e-8884-cbafb20be6f5", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Muscle System Introduction, Section 3.1) EC Coupling in Vertebrate Muscle](https://www.wormatlas.org/hermaphrodite/muscleintro/MusIntroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fe45a0d4-d490-4368-8492-34d425cb152a", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Muscle System Introduction, Section 3.1) EC Coupling in Vertebrate Muscle](https://www.wormatlas.org/hermaphrodite/muscleintro/MusIntroframeset.html)"}, "hash": "a3f3b0b818566b203d48adbafd9c49267dbdf5de7672b492148b63faed572bf1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Depolarization in the T-tubule membrane leads to release of stored Ca++ through the interaction of two proteins. A voltage sensor (dihydropyridine receptor [DHPR] which is a voltage-gated Ca++ channel) in the T-tubule membrane changes conformation in response to the action potential (MusFIG 2A). This conformational change is transmitted to another Ca++ channel (Ryanodine receptor [RyR]) on SR, causing it to open and allowing Ca++ release from SR stores (Ahern et al., 2001). RyRs cluster in the junctions between SR and T-tubules. The direct mechanical interaction between DHPR and RyR is specific for excitation-contraction coupling in vertebrate skeletal muscle. Increased intracellular free calcium then binds to troponin-C (TN-C), part of the regulatory complex attached to the thin (actin) filaments of the sarcomere (Alberts et al., 2002). When Ca++ binds to the TN-C, a conformational change in the regulatory complex relieves the tropomyosin blockage of the interaction between actin and the myosin head. A myosin ATPase located on the myosin head supplies energy for the movement between the myosin heads and actin. The actin and myosin filaments slide past each other (ratcheting) and shorten the  sarcomere length (Alberts et al., 2002). One ratcheting cycle will last as long as the cytosolic Ca++ remains elevated. At the end of contraction, Ca++ is restored to sarcoplasmic reticulum by an ATP-dependent calcium pump.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1435, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c76f1b86-0a13-49c3-864f-b8c13aedb812": {"__data__": {"id_": "c76f1b86-0a13-49c3-864f-b8c13aedb812", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Muscle System Introduction, Section 3.2) EC Coupling in C. elegans Muscle](https://www.wormatlas.org/hermaphrodite/muscleintro/MusIntroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e7e00039-4a72-4ea2-952f-880e8cc4ea03", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Muscle System Introduction, Section 3.2) EC Coupling in C. elegans Muscle](https://www.wormatlas.org/hermaphrodite/muscleintro/MusIntroframeset.html)"}, "hash": "7361d410b9205b21a93f275dc62770059df47a8f2497756a5cf77361ac1fa500", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In C. elegans, sarcoplasmic reticulum (SR) consists of a network of vesicular membranous organelles surrounding the myofilament lattice. The flattened vesicles of SR extend around dense bodies (DBs) and lay adjacent to the apical (hypodermal side) plasma membrane underneath the lattice, where they are localized randomly between DBs (Waterston, 1988) (MusFIG 1) (see Somatic Muscle). A gap of 12-14 nm separates the SR vesicles from the plasma membrane. No equivalent to the T-tubule system exists in C. elegans, possibly because the direct apposition of SR to the plasma membrane abrogates its utility (MusFIG 1A&B) (Waterston, 1988). In C. elegans, the ryanodine receptor (RYR) is encoded by the gene (Maryon et al., 1996; Hamada et al., 2002). Its expression is seen in various muscles including body wall muscles, terminal bulb muscle of the pharynx, vulval and uterine muscles, diagonal muscles of male tail, and the anal sphincter and depressor muscles (Maryon et al., 1998). In somatic muscle, initiation ofunc-68 expression coincides with the first twitching movements of the embryo. Within the body wall muscle, UNC-68 is thought to be localized to SR vesicles, primarily between the rows of dense bodies in the A-band region (Maryon et al., 1998). In contrast to vertebrate muscle, UNC-68 functions to enhance motility but it is not essential for excitation-contraction (E-C) coupling in C. elegans because unc-68 null mutants are still able to propagate coordinated contraction waves, albeit weakly. Following excitatory (cholinergic) neurotransmission at the NMJs of C. elegans, opening of nicotinic AChR (ligand-gated ion channels) on muscle membrane is thought to initiate graded action potentials in muscle arms which then converge and propagate to the contractile compartment of the muscle (Richmond and Jorgensen, 1999; Jospin et al., 2002; Schafer, 2002). There are no voltage-activated Na+ channels in C. elegans and the graded action potentials are thought to be dependent on voltage-activated Ca++ currents across the muscle plasma membrane through L-type channels. It is postulated that activation of these Ca++ channels (similar to dihydropyridine receptor [DHPR] and encoded by the egl-19 gene) on the plasma membrane provides sufficient Ca++ influx from extracellular space to directly initiate a contraction in the nematode body wall muscle where the sarcomeres are placed in close proximity to the plasma membrane (Lee et al., 1997; Maryon et al., 1998; Jospin et al., 2002).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2503, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "930d997e-5c64-4915-9f38-9acf09ed2dcf": {"__data__": {"id_": "930d997e-5c64-4915-9f38-9acf09ed2dcf", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Muscle System Introduction, Section 4) Muscle Arms](https://www.wormatlas.org/hermaphrodite/muscleintro/MusIntroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "263e56b9-2324-4a1c-b3d8-647d5f560949", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Muscle System Introduction, Section 4) Muscle Arms](https://www.wormatlas.org/hermaphrodite/muscleintro/MusIntroframeset.html)"}, "hash": "5cd1fc7e378600a52010e3470585db0eb369a6264fb57f66e9e3144d66ec0c4f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Unlike other organisms where neurons send processes to their target muscle cells to make synapses, neuromuscular junctions (NMJs) of C. elegans are made by arms grown from muscle cells toward motor neurons (MusFIG 3) (Stretton, 1976; Sulston and Horvitz, 1977; Sulston et al., 1983; White et al., 1986; Dixon and Roy, 2005; Dixon et al., 2006). Muscle arms have simple structures made of a stalk and a bifurcated terminus that contacts the neuron. Similar to chemical synapses between neurons, NMJs are made en passant by the innervating neurons onto these muscle arms (White et al., 1986). In a process bundle, each motor neuron process sporadically moves to the outside of the bundle to become accessible to muscle arms in synaptic regions.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 742, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ad463532-17be-4de1-995d-01057e2fa1a5": {"__data__": {"id_": "ad463532-17be-4de1-995d-01057e2fa1a5", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Muscle System Introduction, Section 4.1) Somatic Muscle Arms](https://www.wormatlas.org/hermaphrodite/muscleintro/MusIntroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ae55c4f6-34b6-4e15-9933-6bd823d9aa70", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Muscle System Introduction, Section 4.1) Somatic Muscle Arms](https://www.wormatlas.org/hermaphrodite/muscleintro/MusIntroframeset.html)"}, "hash": "46cf0ffdc4ace74a8d8495d3629ef3083b671c5498da2c960cf6ea00cb44d53a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Muscle arm development is highly stereotypical. Each body wall muscle in the body usually begins by growing a single muscle arm during embryonic development (MusFIG 4). At hatching, muscle cells have on average 1.7 (+/- 0.8) arms per cell (Dixon and Roy, 2005; Dixon et al., 2006). The number of arms increases to three or more by the adult stage, with young adults averaging 4.0 (+/- 1.0) arms per cell (Hall and Hedgecock, 1991; Dixon and Roy, 2005). Individual muscle cells are observed to contain a stereotypical number  of arms, and the muscles lying in rows closest to the dorsal and ventral nerve cords (ventral right and dorsal left quadrants) have significantly more arms than their contralateral homologs. In adult body muscles, individual muscle arms vary in size, shape and branchiness where they contact the longitudinal nerve cords. Viewed in thin sections, the nerve cords are covered by a muscle plate over much of their length, but there are bare patches where no arms contact the nerve cords. The majority of post-embryonic muscle arm outgrowth is coincidental with and dependent on the birth of 53 extra motor neurons and occurs during late-L1 to early-L2 stage (Dixon and Roy, 2005).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1203, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "762fc446-27e2-4aa4-ab63-e230bd9b6299": {"__data__": {"id_": "762fc446-27e2-4aa4-ab63-e230bd9b6299", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Muscle System Introduction, Section 4.1) Somatic Muscle Arms](https://www.wormatlas.org/hermaphrodite/muscleintro/MusIntroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "951ecb2c-0b6a-466d-8801-9b029df42056", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Muscle System Introduction, Section 4.1) Somatic Muscle Arms](https://www.wormatlas.org/hermaphrodite/muscleintro/MusIntroframeset.html)"}, "hash": "db6124bcd743bf15f67da5377d67e3e7204573737bb2d93249048463325ea31b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "There are two suggested mechanisms of muscle arm development. First, during embryogenesis one-two arms are generated passively by migration of myoblasts away from their initial position next to the neurons (MusFIG 4) (Dixon et al., 2006). As myoblasts migrate to their final positions, their cell membranes stay in contact with a motor neuron process, thus generating muscle processes that stretch behind the migrating soma. In contrast, muscle arm growth during larval stages is thought to be an active extension process involving the actin cytoskeleton, extracellular matrix and guidance by chemoattraction (Dixon et al., 2006). Although the specific guidance cue for muscle arm extension is not yet known, the involvement of a guidance cue is supported by two lines of evidence. First, in a kinesin-defective (unc-104) mutant, in which anterograde transport of vesicles is disrupted, some of the dorsal body wall muscle arms extend towards the ventral cord, where dense core vesicles accumulate within motor neuron cell bodies (Hall and Hedgecock, 1991). In this mutant, it is suggested that the release of the muscle attractant occurs close to the neuron cell body where the vesicles are sequestered. Second, in unc-6 or unc-5 mutants, in which formation of motor neuron process bundles is erratic, body wall muscle arms extend to the lateral regions where the errant motor neuron processes are located (Hedgecock et al., 1990).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1432, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a3a88e65-d050-4a7d-9381-ad526d2bce72": {"__data__": {"id_": "a3a88e65-d050-4a7d-9381-ad526d2bce72", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Muscle System Introduction, Section 4.1) Somatic Muscle Arms](https://www.wormatlas.org/hermaphrodite/muscleintro/MusIntroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "efa70458-694c-4d11-8c8f-53a3a1f1fba1", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Muscle System Introduction, Section 4.1) Somatic Muscle Arms](https://www.wormatlas.org/hermaphrodite/muscleintro/MusIntroframeset.html)"}, "hash": "270b59eb7ec014d637af2eeff65e72702beeac5c1c623af9adfca6322b9566e8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Development of muscle arms from the head and neck muscles to the nerve ring (NR) may occur principally by the passive extension mechanism. Early in embryogenesis, head and neck muscle cells directly surround the pharynx. It is suggested that when these muscle cells later migrate towards the periphery, as the first amphid axons extend to initiate the formation of the nerve ring, they leave an arm behind, next to the pharynx (MusFIG 4) (C. Norris, pers. comm.). The arms left behind from neck muscles, which are located posterior to the GLR cells, are then thought to grow anteriorly to reach the nascent nerve ring actively. The head and neck muscle arms together define a fairly precise topological map (both circumferential and antero-posterior) of motor neurons and their target muscles along the inner surface of the nerve ring (MusFIG 5A&B, MusFIG 5C-F, MusFIG 5G and MusMOVIE 1) (White et al., 1986). GLR cells are suggested to function as mesodermal scaffolding cells that guide the muscle arms to their appropriate territories for development of this motor map (see Somatic Muscle and GLR Cells). In the adult, the motor neuron axons that innervate the head and neck muscles are located in the innermost regions of the nerve ring except those of RIML/R motor neurons, which run more laterally within the nerve ring. The head muscle arms, which receive innervation from RIML/R, hence make small branches, which may penetrate the basal lamina in four places to contact RIML/R axons (MusFIG 5A).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1503, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9f9c78f3-133e-44ab-8e86-be9b68a3a680": {"__data__": {"id_": "9f9c78f3-133e-44ab-8e86-be9b68a3a680", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Muscle System Introduction, Section 4.1) Somatic Muscle Arms](https://www.wormatlas.org/hermaphrodite/muscleintro/MusIntroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4583c6b6-37d1-46ae-9874-e7b32e4969c1", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Muscle System Introduction, Section 4.1) Somatic Muscle Arms](https://www.wormatlas.org/hermaphrodite/muscleintro/MusIntroframeset.html)"}, "hash": "2690ea4c2a3d7cdd07b452afc99938231453fad971d9a38a99297e24f7f2c785", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In somatic muscle, the distal portions of muscle arms interdigitate abundantly in regions of neuromuscular junctions (MusFIG 6A-F, MusFIG 6G-K and MusMOVIE 2). The interdigitated muscle arms also make gap junctions to one another that are suggested to have a role in synchronous contractions of body muscles during embryonic elongation as well as in synchronizing the activity of left and right quadrants during normal body motion (Hall and Hedgecock, 1991) (see also Gap Junctions).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 483, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2fbe76dd-4b5a-4969-80fb-b2695a724656": {"__data__": {"id_": "2fbe76dd-4b5a-4969-80fb-b2695a724656", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Muscle System Introduction, Section 4.1) Somatic Muscle Arms](https://www.wormatlas.org/hermaphrodite/muscleintro/MusIntroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "08412c19-da3d-43fb-a4ff-96773242e5d3", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Muscle System Introduction, Section 4.1) Somatic Muscle Arms](https://www.wormatlas.org/hermaphrodite/muscleintro/MusIntroframeset.html)"}, "hash": "98485560e1b76c950adeb3b1ed1e9f345a6af75d000fb65a8b0ab417a8524f86", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "MusMOVIE 2: Interdigitation of neck muscle arms. Illustrations are reconstructions made from tracings of serial section TEMs (by Tylon Stephney) of neck muscles (based on [MRC] N2U series) ( Liu et al., 2007 ). Reconstruction was created by Huawei Weng using Imaris software. Click on image to play movie.\n\n 4.2 Nonstriated Muscle Arms", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 335, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f5b8aa58-7311-4ea9-895d-b05214ef6095": {"__data__": {"id_": "f5b8aa58-7311-4ea9-895d-b05214ef6095", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Muscle System Introduction, Section 4.2) Nonstriated Muscle Arms](https://www.wormatlas.org/hermaphrodite/muscleintro/MusIntroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e6bc1a14-5dd6-4594-8523-1ef7396ea491", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Muscle System Introduction, Section 4.2) Nonstriated Muscle Arms](https://www.wormatlas.org/hermaphrodite/muscleintro/MusIntroframeset.html)"}, "hash": "af45891a60c78af9baebf75e7ba7c8e525dd5daa06a62fa600211493bf4c7ce4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Pharyngeal muscles do not extend muscle arms. No epithelial cells separate pharyngeal muscle from the pharyngeal nerves, placing many motor neurons in direct apposition to their target muscles for synaptic innervation. Some nerve bundles, such as M2 neurons, actually pass inside the muscles and make neuromuscular junctions to pharyngeal muscles inside the muscle cells (see Alimentary system - Pharynx).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 405, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a4f6f719-4f66-4876-a3f7-f7b9b713fc6c": {"__data__": {"id_": "a4f6f719-4f66-4876-a3f7-f7b9b713fc6c", "embedding": null, "metadata": {"source document": "WormAtlas Handbook: [Muscle System Introduction, Section 4.2) Nonstriated Muscle Arms](https://www.wormatlas.org/hermaphrodite/muscleintro/MusIntroframeset.html)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "658c0154-194f-4389-bf29-91151dd07eed", "node_type": "4", "metadata": {"source document": "WormAtlas Handbook: [Muscle System Introduction, Section 4.2) Nonstriated Muscle Arms](https://www.wormatlas.org/hermaphrodite/muscleintro/MusIntroframeset.html)"}, "hash": "cacac3fa0ee3bd6135e4f6f7d7f901ca511e0eb097cd7c6ed18e949e3b7511a3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Among sex-specific hermaphrodite muscles, the only obvious muscle arms are made by vm1R muscles. These extend arms to the ventral cord to  receive synaptic input from the ventral cord motor neurons VA7, VB6, and VD7 (see Reproductive system - Egg-laying Apparatus ) (White et al., 1986). The muscle arms from the anal depressor muscle, anal sphincter muscle and two stomatointestinal cells are quite long. All arms must extend to the preanal ganglion where they receive synapses from the DVB neuron (see Nonstriated Muscle).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 524, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4b101b73-41be-4683-9367-77d8127955ee": {"__data__": {"id_": "4b101b73-41be-4683-9367-77d8127955ee", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.1, para 1](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "efa6e459-4731-47ec-9c23-d5e6f1ea9ab5", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.1, para 1](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "e74d61839406a6bc5a5745a8216e902f396d6e75cad24c547b1f1b1df1fae83b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# A Transparent Window into Biology: A Primer on *Caenorhabditis elegans*", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 73, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "83177e30-3187-45f3-96a0-e4ac2e8b4fc0": {"__data__": {"id_": "83177e30-3187-45f3-96a0-e4ac2e8b4fc0", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.1, para 2](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "248cf090-3741-42a0-91fc-2f5897ed9927", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.1, para 2](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "3443467a57c73aec2dc4b5a2b3333072321d65614c05a5a3926c3523766dda2c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Ann K. Corsi,\\*^,1 Bruce Wightman,^\u2020,1 and Martin Chalfie^\u2021,1", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 61, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "be0b8978-0e50-410f-9f5a-4ec2174072c0": {"__data__": {"id_": "be0b8978-0e50-410f-9f5a-4ec2174072c0", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.1, para 3](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9668a7b3-3942-43c4-b57a-cba71da542f5", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.1, para 3](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "17b2d0bfca22e1736a115b2cfd30c769948f1ead03dc237d77c78e9d94fd442f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "\\*^Biology Department, The Catholic University of America, Washington, DC 20064, \u2020Biology Department, Muhlenberg College, Allentown, Pennsylvania 18104, and \u2021Department of Biological Sciences, Columbia University, New York, New York 10027", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 238, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2729b665-b382-4ac4-9f2d-0acda0e66302": {"__data__": {"id_": "2729b665-b382-4ac4-9f2d-0acda0e66302", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.1, para 5](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "68948bbe-14b2-459e-b66b-42536b4c0fa5", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.1, para 5](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "e98818588150f8d023d06ae83fe310a6f039e48bfa6486bb8cda07702f2b929c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Here, for the first time, GENETICS and WormBook, the online review of *C. elegans* biology, co-publish an article. As mission-driven, community publishers, we seek to provide the most widely accessible resource available to researchers. We wish to thank Jane Mendel, WormBook Editor, for her dedication to this collaboration, and Marty Chalfie for his vision.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 359, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d998ba17-6ae8-4967-bb5a-b309f5919f69": {"__data__": {"id_": "d998ba17-6ae8-4967-bb5a-b309f5919f69", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.1, para 6](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "92931bcb-88ca-4884-b8be-7a361789858a", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.1, para 6](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "09c651f239e99b129ba54ed1490473d15aaa8da3bf89e4b805cd41f30ab38c03", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**ABSTRACT** A little over 50 years ago, Sydney Brenner had the foresight to develop the nematode (round worm) *Caenorhabditis elegans* as a genetic model for understanding questions of developmental biology and neurobiology. Over time, research on *C. elegans* has expanded to explore a wealth of diverse areas in modern biology including studies of the basic functions and interactions of eukaryotic cells, host\u2013parasite interactions, and evolution. *C. elegans* has also become an important organism in which to study processes that go awry in human diseases. This primer introduces the organism and the many features that make it an outstanding experimental system, including its small size, rapid life cycle, transparency, and well-annotated genome. We survey the basic anatomical features, common technical approaches, and important discoveries in *C. elegans* research. Key to studying *C. elegans* has been the ability to address biological problems genetically, using both forward and reverse genetics, both at the level of the entire organism and at the level of the single, identified cell. These possibilities make *C. elegans* useful not only in research laboratories, but also in the classroom where it can be used to excite students who actually can see what is happening inside live cells and tissues.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1317, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "743b6a2f-6830-4863-85ee-003197b93ccc": {"__data__": {"id_": "743b6a2f-6830-4863-85ee-003197b93ccc", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.1, para 7](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e91fc9a0-bcb9-43f6-80da-2e92f2a7725c", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.1, para 7](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "b61131ca26641f330593cd0b98fa921b205607a43afecb68c6f77f9c669e8573", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**KEYWORDS** *C. elegans*; nematodes; Primer; single-cell analysis; transparent genetic system", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 94, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e1a3b408-be66-460f-b4ad-4586717c0e81": {"__data__": {"id_": "e1a3b408-be66-460f-b4ad-4586717c0e81", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.1, para 8](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5cec9910-f260-4f4f-b07d-f606cd49f452", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.1, para 8](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "c8aa880cb4c868c021a291821870cc844b391dc594b6397944bb1b93eb0b63a0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## TABLE OF CONTENTS", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 20, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "dc0d5522-ad01-4043-a164-3686e1bf7bcf": {"__data__": {"id_": "dc0d5522-ad01-4043-a164-3686e1bf7bcf", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.1, para 9](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e5766de8-b2d3-4e35-8282-2a1d1147e60c", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.1, para 9](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "28ff56d1dd23f05f46ebfd85e5c2f8925e8a06ca7e4e2b1609e7fdaa805a29f1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* Abstract 387\n* Introduction 388\n* *C. elegans* Basics 389\n  * Growth and maintenance 389\n  * Sexual forms and their importance 390\n  * Life cycle 391\n* *C. elegans* Genetics 391\n  * Continued", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 193, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "dfabf3f2-862d-49e0-861d-1d324cb8c1fd": {"__data__": {"id_": "dfabf3f2-862d-49e0-861d-1d324cb8c1fd", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.1, para 10](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "db9fa9c4-80be-438e-b16a-855deae2d9af", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.1, para 10](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "5e10194770ab034026e04923c7a3c9e76d0a61a5bf0043538e39aaaba0dd1cee", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Copyright \u00a9 2015 Corsi, Wightman, and Chalfie\ndoi: 10.1534/genetics.115.176099\nThis is an open-access article distributed under the terms of the Creative Commons Attribution Unported License (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 192, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8f7c0111-91ab-4f9c-a90a-26689c796f6c": {"__data__": {"id_": "8f7c0111-91ab-4f9c-a90a-26689c796f6c", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.1, para 11](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3a2c0516-9aee-4584-83bb-c5d3e75fae63", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.1, para 11](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "b0a25d03fcba8e463cb259534063e12f0edd90632cdaeab5bebb963950d303ff", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. ^1Corresponding authors: Biology Department, The Catholic University of America, Washington, DC 20064. E-mail:", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 237, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9f5a46ab-819e-48d3-a541-b61a5c4a5648": {"__data__": {"id_": "9f5a46ab-819e-48d3-a541-b61a5c4a5648", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.1, para 12](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6e85ddfd-9696-4158-82d9-f4955d4d3a37", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.1, para 12](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "d1f3ee57424c02608167712b8104b76ea3ca161cb9e4ee83feadf4b0a85227b0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "; Biology Department, Muhlenberg College, Allentown, Pennsylvania 18104. E-mail:", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 80, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a3e647aa-3937-4067-85e9-19bc91b56a52": {"__data__": {"id_": "a3e647aa-3937-4067-85e9-19bc91b56a52", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.1, para 13](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d2912c9e-ac4a-4a5e-a872-3f1616b16360", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.1, para 13](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "5f86464f44a421446292e1bd9b3985b1e8bd712799832c6c6974946996dc3d00", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "; and 1012 Fairchild Center, MC no. 2446, 1212 Amsterdam Ave., Columbia University, New York, NY 10027. E-mail:", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 111, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "870dcd25-32c1-45cf-a796-0c0df9ca3492": {"__data__": {"id_": "870dcd25-32c1-45cf-a796-0c0df9ca3492", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.2, para 0](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a7c9262f-f5de-4b70-a996-7e1c3d8a1cc8", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.2, para 0](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "77b000c6f4950d1dd40ba30bde4140e610210b1e13d7e72f3c8da1aab79e73f5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# CONTENTS, continued", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 21, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "17a5b962-7273-419a-b73e-4a049c515d96": {"__data__": {"id_": "17a5b962-7273-419a-b73e-4a049c515d96", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.2, para 1](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "12a691df-ba02-4478-a547-a8fa4657b898", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.2, para 1](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "1f6b42af2fd0314570c6e4588e007708b02b29770bdb1f43b4a021657192371a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* Why Choose C. elegans? 393\n* C. elegans Tissues 395\n  * Epidermis: a model for extracellular matrix production, wound healing, and cell fusion 395\n  * Muscles\u2014controlling animal movement 396\n  * The digestive system\u2014a model for organogenesis and pathogenesis 396\n  * The nervous system\u2014small yet complex 396\n  * Reproductive tissue\u2014sex-specific anatomy 398\n* The C. elegans Genome 399\n* Caenorhabditis Ecology and Evolution 399\n* Brief History of C. elegans Research and Key Discoveries 400\n* The C. elegans Community 402\n* Acknowledgments 403\n* Literature Cited 403", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 568, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c85bb208-6c78-462c-a82c-57f8aed7f851": {"__data__": {"id_": "c85bb208-6c78-462c-a82c-57f8aed7f851", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.2, para 2](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a0a9a26e-8d25-4429-bdf1-316855e44d02", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.2, para 2](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "e0ed360bad923f22bcdb76ba47db5c0a9ae404366c2f46ee04f51a016cc1e15d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "IN 1963, Sydney Brenner sent a letter to Max Perutz, the chairman of the Medical Research Council\u2019s Laboratory of Molecular Biology (LMB), detailing his concerns that the \u201cclassical problems of molecular biology have either been solved or will be solved in the next decade\u201d and proposing that the future of molecular biology lies in the extension to other fields, \u201cnotably development and the nervous system\u201d (Brenner 1988, 2002). With the simplicity and power of prokaryotic genetics in mind, he proposed that a nematode (round worm), *Caenorhabditis briggsae*, would be an ideal system in which to tackle these problems. Later, he settled on the related nematode *C. elegans* as the focus of his efforts because the *elegans* strain grew better than the *briggsae* isolate in Brenner\u2019s laboratory (F\u00e9lix 2008). Today, *C. elegans* is actively studied in over a thousand laboratories worldwide (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 896, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9e85e799-e7fa-4733-a265-1464069a7e49": {"__data__": {"id_": "9e85e799-e7fa-4733-a265-1464069a7e49", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.2, para 4](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "12f2ff3b-497c-4e70-9ba2-2a84ea5557c5", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.2, para 4](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "04859187fd8f150af612668ca171845e566c2946802aa3c3956be6aea25f76c8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ") with over 1200 *C. elegans* research articles published each year for the last 5 years.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 89, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9a8f8808-ee59-42d6-815d-5bfa75444bc8": {"__data__": {"id_": "9a8f8808-ee59-42d6-815d-5bfa75444bc8", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.2, para 5](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "56647db8-e389-449e-bc6c-cb369b29d038", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.2, para 5](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "17f6a63461926744e6e7b2c35f9e45c0c41546285ef10c6c0e44d4ad1570a9ca", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "*C. elegans* is a tiny, free-living nematode found worldwide. Newly hatched larvae are 0.25 mm long and adults are 1 mm long. Their small size means that the animals usually are observed with either dissecting microscopes, which generally allow up to 100X magnification, or compound microscopes, which allow up to 1000X magnification. The dissecting microscope is used to observe worms on Petri dishes (Figure 1, A and B) as they move, eat, develop, mate, and lay eggs (for movies showing these features, see", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 508, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b54ec6c6-1a1f-4456-9127-fb326263dfb9": {"__data__": {"id_": "b54ec6c6-1a1f-4456-9127-fb326263dfb9", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.2, para 6](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f55e433c-3b42-4d12-b627-638576586860", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.2, para 6](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "e2bb5a71d1c4569a43b0306bbdd0eef995c6d41eb40eb520751033e22a8121e0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "). A compound or confocal microscope allows observation at much finer resolution (Figure 1C), permitting researchers to perform experiments that address questions related to cell development and function at single-cell resolution. Because *C. elegans* is transparent, individual cells and subcellular details are easily visualized using Nomarski (differential interference contrast, DIC) optics (Figure 1C). Enhanced detail can be discerned by using fluorescent proteins to tag proteins or subcellular compartments (Figure 1D). Fluorescent proteins can also be used to study developmental processes, screen for mutants affecting cell development and function, isolate cells, and characterize protein interactions *in vivo* (Chalfie *et al.* 1994; Boulin *et al.* 2006; Feinberg *et al.* 2008).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 793, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6e44a434-4eee-4c25-9df9-24bd842341e3": {"__data__": {"id_": "6e44a434-4eee-4c25-9df9-24bd842341e3", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.2, para 7](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e845caec-e15f-4069-9a10-06d870874bfe", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.2, para 7](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "aa5bd7e90548f5a421860438dfa2abe4319216b3c99a9afbdc358e37e5977568", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "*C. elegans* has a rapid life cycle (3 days at 25\u00b0 from egg to egg-laying adult) and exists primarily as a self-fertilizing hermaphrodite, although males arise at a frequency of <0.2% (Figure 2). These features have helped to make *C. elegans* a powerful model of choice for eukaryotic genetic studies. In addition, because the animal has an invariant number of somatic cells, researchers have been able to track the fate of every cell between fertilization and adulthood in live animals and to generate a complete cell lineage (Sulston and Horvitz 1977; Kimble and Hirsh 1979; Sulston *et al.* 1983). Researchers have also reconstructed the shape of all *C. elegans* cells from electron micrographs, including each of the 302 neurons of the adult hermaphrodite (White *et al.* 1986) and the posterior mating circuit in the adult male (Jarrell *et al.* 2012). These reconstructions have provided the most complete \u201cwiring diagrams\u201d of any nervous system and have helped to explain how sexual dimorphism affects neuronal circuits. Moreover, because of the invariant wild-type cell lineage and neuroanatomy of *C. elegans*, mutations that give rise to developmental and behavioral defects are readily identified in genetic screens. Finally, because *C. elegans* was the first multicellular organism with a complete genome sequence (*C. elegans* Sequencing Consortium 1998), forward and reverse genetics have led to the molecular identification of many key genes in developmental and cell biological processes.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1507, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2abebc28-f384-4cc1-a70d-caddd2a427ce": {"__data__": {"id_": "2abebc28-f384-4cc1-a70d-caddd2a427ce", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.2, para 8](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7770f585-101d-4743-a680-231a7aa9abb0", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.2, para 8](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "4983e6b3de928de5e87561e4b6193f6536199445e5f87a1db119425cdcbf5249", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The experimental strengths and the similarities between the cellular and molecular processes present in *C. elegans* and other animals across evolutionary time (metabolism,", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 172, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5f4b0672-f64d-4980-9bde-29ab51d1d23e": {"__data__": {"id_": "5f4b0672-f64d-4980-9bde-29ab51d1d23e", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.3, para 0](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "492d40a1-9f60-405a-939f-072578bb7e81", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.3, para 0](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "5d865b87efa354b45a2348faaeeb7923507447ee0d2b6c7d20151bad3b47e5ee", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Figure 1 Observing *C. elegans*. (A) Petri dishes sitting on the base of a dissecting stereomicroscope. Bacterial lawns are visible on the surface of the agar inside the dishes but the *C. elegans* are too small to be seen in this view. (B) *C. elegans* viewed through the dissecting microscope. The two adults are moving in this view. Tracks in the plate indicate where animals have traveled on the bacterial lawn. (C) An adult hermaphrodite is viewed in a compound microscope. In all pictures, anterior is to the left and ventral is on the bottom. *C. elegans* moves on either its left or right side; in this image the surface facing the viewer is the left side. Because the animals are transparent, one can see, from left to right on the ventral side, developing oocytes in the gonad (rectangular cells with a clear, circular nucleus inside) followed by the spermatheca (where oocytes are fertilized), and multiple embryos in the uterus. (D) Fluorescent image showing the nervous system labeled with a GFP reporter (*sto-6::gfp*). Photo credits: (C) Original (modified here): B. Goldstein; (D) J. Kratz.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1106, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "175598d1-3c63-445e-9358-bb3b6e2e50ce": {"__data__": {"id_": "175598d1-3c63-445e-9358-bb3b6e2e50ce", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.3, para 1](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "490b87a5-b240-435b-964b-d9cbcb423e85", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.3, para 1](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "dca4f182bc82982143217e4d6f1d87e8960b1540560a5f589c7dcd147bdee5ea", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* organelle structure and function, gene regulation, protein biology, etc.) have made *C. elegans* an excellent organism with which to study general metazoan biology. At least 38% of the *C. elegans* protein-coding genes have predicted orthologs in the human genome (Shaye and Greenwald 2011), 60\u201380% of human genes have an ortholog in the *C. elegans* genome (Kaletta and Hengartner 2006), and 40% of genes known to be associated with human diseases have clear orthologs in the *C. elegans* genome (Culetto and Sattelle 2000). Thus, many discoveries in *C. elegans* have relevance to the study of human health and disease.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 623, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "12ab3156-4d0f-4ab0-8fe8-5bfb9e4a51d6": {"__data__": {"id_": "12ab3156-4d0f-4ab0-8fe8-5bfb9e4a51d6", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.3, para 2](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b8429de7-da34-4cde-aa08-4de22ed6520c", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.3, para 2](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "6d0aeff0b110c1071ba70f64c56464c5d147a4930c2a1075e684de7170549cc1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## *C. elegans* Basics", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 22, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6d3551cd-b111-4eec-8d04-5f4a7c27845e": {"__data__": {"id_": "6d3551cd-b111-4eec-8d04-5f4a7c27845e", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.3, para 3](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fa49b7c2-537d-460d-b3f6-5d805a2db13d", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.3, para 3](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "1b0506410ce06209e59eab962fe3015203035d7a2459e8fb3b7943204bf93d8f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Growth and maintenance", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 26, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f7620828-a9c7-477a-93da-ce4b6e556375": {"__data__": {"id_": "f7620828-a9c7-477a-93da-ce4b6e556375", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.3, para 4](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "457671b5-2deb-4d98-97ae-3e89556ce57c", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.3, para 4](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "fe758316fcbfa5eb4b443e940edbaf81eb4466a067ab444057ce33eb78a001ee", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "*C. elegans*, although often mischaracterized as a soil nematode, can most easily be isolated from rotting vegetable matter, which contains an ample supply of their bacterial food source (Barri\u00e8re and F\u00e9lix 2014). In the laboratory, animals are normally grown on agar plates containing a lawn of the bacterium *Escherichia coli*. Once the animals deplete the bacteria, they utilize their fat supply. Without food, the development of young larval-stage animals is arrested. As a result of entering this stasis, animals can survive for at least a month (often starved plates can be usefully kept for up to 6 months at 15\u00b0), and as stocks, they do not require constant feeding. Whenever healthy, growing animals are needed, a piece of the agar from the old plate can be transferred to a new plate with bacteria. The animals move to the new bacteria and resume their development.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 875, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8987abe8-27fb-468e-a9fc-77f1dd6c178b": {"__data__": {"id_": "8987abe8-27fb-468e-a9fc-77f1dd6c178b", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.3, para 5](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3c93a44c-4228-4be3-9949-3d6e5111db1a", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.3, para 5](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "2f1e8733dd82e3e5558616fe4f8db09bdf2a05ed3ee95d61b13947fa84f721e7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Several other features greatly facilitate the maintenance of *C. elegans* stocks and their experimental use. First, because *C. elegans* is a self-fertilizing hermaphrodite (see the following section), a single animal can populate a plate. Second, animal populations can be frozen for years and revived when needed. Third, the animal\u2019s small size means that many can be grown in a small space. Fourth, animals can be grown at temperatures ranging from 12\u00b0 to 25\u00b0; their Q10 for growth is \\~2 (that is, an increase of 10\u00b0 speeds up growth twofold). Growth at different temperatures makes it possible to control the rate of animal development and assists in the isolation and use of temperature-sensitive mutants. Continual growth above 25\u00b0 is not possible because the animals become sterile. The upper temperature limit can be a problem if animals are kept on bench tops (instead of temperature-controlled incubators) in rooms that are too warm. Shorter exposures to higher temperatures are possible for heat shock experiments and to increase production of", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1055, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0f951354-82bd-42ce-b4a4-8253b5b128cd": {"__data__": {"id_": "0f951354-82bd-42ce-b4a4-8253b5b128cd", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.4, para 0](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "afa656c0-3d8c-4e3b-a0d5-53a6a285b256", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.4, para 0](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "09bec02abd8189ab7f9bd8ab957a96511a54fdbddd0fe87abf7a2b2a513a41d1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Figure 2 Life cycle of C. elegans. Animals increase in size throughout the four larval stages, but individual sexes are not easily distinguished until the L4 stage. At the L4 stage, hermaphrodites have a tapered tail and the developing vulva (white arrowhead) can be seen as a clear half circle in the center of the ventral side. The males have a wider tail (black arrowhead) but no discernible fan at this stage. In adults, the two sexes can be distinguished by the wider girth and tapered tail of the hermaphrodite and slimmer girth and fan-shaped tail (black arrowhead) of the male. Oocytes can be fertilized by sperm from the hermaphrodite or sperm obtained from males through mating. The dauer larvae are skinnier than all of the other larval stages. Photographs were taken on Petri dishes (note the bacterial lawns in all but the dauer image). Bar, 0.1 mm.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 864, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0535ce07-fbc5-4ba2-ab6e-a864f7474be8": {"__data__": {"id_": "0535ce07-fbc5-4ba2-ab6e-a864f7474be8", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.4, para 1](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "186020bf-067b-490f-b0a4-1408a3437362", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.4, para 1](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "aa66a8bd09f9b4cbb845488bb319fac58275608f3b239bb8c7c450b20b4ab282", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* males (Sulston and Hodgkin 1988). Fifth, animals can be synchronized by isolating newly hatched larvae or by treating gravid adults with bleach (which decontaminates by killing everything but embryos) and isolating eggs, which are resistant to bleach treatment. Sixth, to facilitate biochemical studies, animals can be grown in bulk in liquid medium. \u201cWorm sorters\u201d such as the COPAS Biosorter are also available to quickly select large quantities of individual worms with desired characteristics. Finally, one does not need especially expensive equipment beyond a good dissecting microscope and a compound microscope to work with this animal. Overall, the animals are inexpensive and convenient to maintain.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 710, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6d0b372c-977e-4d22-b91c-3b800df57744": {"__data__": {"id_": "6d0b372c-977e-4d22-b91c-3b800df57744", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.4, para 2](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "26225978-8480-4329-bad0-1d192842731d", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.4, para 2](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "e31daf7ea3b2d4301821788b18f3b270d08d947f56d83955ca079832a8e10db2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Sexual forms and their importance", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 36, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2ec49e8e-6669-41c5-b2e7-962e8ffce0e2": {"__data__": {"id_": "2ec49e8e-6669-41c5-b2e7-962e8ffce0e2", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.4, para 3](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "aa925fff-0501-4efb-95e5-a50944a17b69", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.4, para 3](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "9c7de95237d11fcc93d0b89b6068e2fcfd77c61a181fd22e71cc69e115a30d64", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Wild-type *C. elegans* has two sexual forms: self-fertilizing hermaphrodites and males (Figure 2 and Figure 3, A and B). The gonad of hermaphrodites forms an ovotestis that first produces haploid amoeboid sperm that are stored in the spermatheca in the L4 stage and then near adulthood the germ line switches fate to produce much larger oocytes. Essentially hermaphrodites are females whose gonads temporarily produce sperm before they produce oocytes. Hermaphrodites can produce up to 300 self-progeny that are fertilized by the stored sperm. If mated with males, hermaphrodites are capable of producing \\~1000 offspring, indicating that hermaphrodite-produced sperm is a limiting factor in self-fertilization. Both sexes are diploid for the five autosomal chromosomes. The sexes differ in that hermaphrodites have two X chromosomes and males have a single X chromosome\u2014*C. elegans* has no Y chromosome\u2014and the genotype of males is referred to as XO. Sex is determined by the X to autosome (X:A) ratio (Zarkower 2006). The majority of offspring produced by self-fertilization are hermaphrodites; only 0.1\u20130.2% of the progeny are males due to rare meiotic nondisjunction of the X chromosome. Because hermaphrodites make their own sperm, in genetic crosses self-progeny (oocytes fertilized by the hermaphrodite\u2019s sperm) need to be distinguished from cross-progeny. For example, when hermaphrodites homozygous for a recessive mutation causing a visible mutant phenotype are mated to wild-type males, the self-progeny hermaphrodites show the mutant phenotype and the cross-progeny hermaphrodites do not.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1600, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b548728d-24fe-4e03-94f7-162db51e8c46": {"__data__": {"id_": "b548728d-24fe-4e03-94f7-162db51e8c46", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.4, para 4](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0d63c6a2-cca3-4c87-b701-31fc7900ddef", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.4, para 4](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "d33d4f69f365b5cab14d177940aa73323028f36d9f9940527392cd3be3dcb6ee", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Self-fertilizing hermaphrodites provide several advantages for genetic analysis. First, self-fertilization (often referred to as selfing) simplifies maintaining stocks because a single animal can give rise to an entire population. Second, as Brenner (1974) has written, \u201cthe animals are driven to homozygosity,\u201d i.e., populations of hermaphrodites tend to lose heterozygotes (because hermaphrodites cannot mate with other hermaphrodites). Thus, strains that are mutagenized are essentially isogenic. Third, selfing follows the standard Mendelian rules of segregation, so a parent that is heterozygous for a recessive trait will produce the standard 1:2:1 pattern of segregation, such that 25% of the progeny will be homozygous for the mutant allele and display the autosomal recessive trait. Thus, selfing reduces greatly the effort needed to find such mutants. Fourth, mutants with neuromuscular defects that impair the ability to mate can still be maintained in the laboratory. In fact, only 11 of the 302 nerve cells of the hermaphrodite: eight ADF, ASG, ASI, and ASJ neurons, which when killed as a group cause the animals to become dauer larvae (Bargmann and Horvitz 1991), the two CAN cells (Forrester and Garriga 1997), and the M4 neuron in the pharynx (Avery and Horvitz 1989) are known to be essential to support development to the reproductive adult stage. Fifth, the viability of even severely defective mutants and their ability to self-fertilize allows for easy screens for modifier (enhancer and suppressor)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1521, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0a24687b-c294-4d30-9aa9-31f995bb1896": {"__data__": {"id_": "0a24687b-c294-4d30-9aa9-31f995bb1896", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.5, para 0](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9096a9af-a237-41f8-bd8e-1124238e81b2", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.5, para 0](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "ba0abe9a5023d3ba89288b51c4c69d42e42d28f4d4b8d9b46a8477931a192d93", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Figure 3 C. elegans anatomy. Major anatomical features of a hermaphrodite (A) and male (B) viewed laterally. (A) The dorsal nerve cord (DNC) and ventral nerve cord (VNC) run along the entire length of the animal from the nerve ring. Two of the four quadrants of body wall muscles are shown. (B) The nervous system and muscles are omitted in this view, more clearly revealing the pharynx and intestine. (C) Cross-section through the anterior region of the C. elegans hermaphrodite (location marked with a black line in A) showing the four muscle quadrants surrounded by the epidermis and cuticle with the intestine and gonad housed within the pseudocoelomic cavity. Images are modified from those found at [www.wormatlas.org](http://www.wormatlas.org) (Altun et al. 2002\u20132015).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 778, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "05d589ea-5f44-46fb-b2db-add1bef07bbb": {"__data__": {"id_": "05d589ea-5f44-46fb-b2db-add1bef07bbb", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.5, para 2](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "332a01f2-d42d-4945-955e-d0fa94ecb26a", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.5, para 2](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "ff5db730cd18ed6f8bdb3ccecc1f1c63b172a0a2ace165d337c84a3901192686", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* mutations. Such screens have been exceptionally useful and informative. For example, *lin-12* mutants (*C. elegans* nomenclature is outlined in Box 1) are defective in vulval development and components of the LIN-12/Notch signaling pathway have been identified with both suppressor and enhancer screens (Greenwald and Kovall 2013).\n* Males are important because they allow the exchange of genetic material needed to generate animals with different genetic compositions and to map genes. Indeed, the animal has evolved to take advantage of the genetic contribution of rare males by using male (outcross) sperm before using hermaphrodite (self) sperm (Ward and Carrel 1979). Thus, if males are capable of mating, cross-progeny prevail (to help males find hermaphrodites, researchers use Petri plates with a small spot of bacteria).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 831, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e5a09695-0880-4ce0-a8b1-ec2c25274c72": {"__data__": {"id_": "e5a09695-0880-4ce0-a8b1-ec2c25274c72", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.5, para 3](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f565ceb7-996d-4d2c-90f9-8d074481df8b", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.5, para 3](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "0a6b460994fbbe93948c8c873b29c3e9a4d7c98fd8446c7fc3db45a8d2162c0a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Life cycle", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 13, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "60d066e8-5f63-402a-a79b-22d70d93c1f6": {"__data__": {"id_": "60d066e8-5f63-402a-a79b-22d70d93c1f6", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.5, para 4](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "720d9997-4ff6-46ea-b369-a03a119e1a2c", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.5, para 4](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "6ab6407755eea91e5480fb016b3ed8c278530a014c40734c9014ff909557e208", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "*C. elegans* embryogenesis takes \\~16 hr at 20\u00b0 (all of the subsequent times are also for development at 20\u00b0) (Figure 2). A virtually impermeable eggshell is made after fertilization, allowing the embryo to develop completely independent of the mother. However, embryos are usually retained within the hermaphrodite until about the 24-cell stage at which time they are laid. The hermaphrodite embryo hatches with 558 nuclei (some nuclei are in multinuclear syncytia, so the cell count is lower) and becomes a first stage (L1) larva. The animals begin to eat and develop through four larval stages (L1\u2013L4). The L1 stage is \\~16 hr long; the other stages are \\~12 hr long. Each stage ends with a sleep-like period of inactivity called lethargus (Raizen et al. 2008) in which a new cuticle (outer collagenous layer) is made. Lethargus ends with the molting of the old cuticle. Approximately 12 hr after the L4 molt, adult hermaphrodites begin producing progeny for a period of 2\u20133 days until they have utilized all of their self-produced sperm; additional progeny can be generated if the sperm-depleted hermaphrodite mates with a male. After the reproductive period, hermaphrodites can live several more weeks before dying of senescence.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1234, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "97d9acc7-c1e1-4a7f-bf8e-a55245c9838f": {"__data__": {"id_": "97d9acc7-c1e1-4a7f-bf8e-a55245c9838f", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.5, para 5](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "60d35880-cd31-4f59-a276-df6f5d2e148c", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.5, para 5](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "09dc8b11eee7960e5020e58c554e808f250f025c4815a381735250600983d3fb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "When bacteria are depleted and the animals are crowded, L2 larvae activate an alternative life cycle (Hu 2007) and molt into an alternative L3 larval stage called the \u201cdauer\u201d larva (\u201cdauer\u201d in German means \u201clasting\u201d; the signal is actually processed by L1 animals, but its results are not seen until the so-called \u201cL2d\u201d stage; Golden and Riddle 1984). The dauer larva cuticle completely surrounds the animal and plugs the mouth preventing the animal from eating and thereby arresting development. The dauer cuticle has enhanced resistance to chemicals, so it provides the dauer with greater protection against environmental stresses and caustic agents. Dauer larvae can survive for many months and are the dispersal form most commonly encountered in the wild. When the dauer larvae are transferred onto plates with bacteria, they shed their mouth plugs, molt, and continue their development as slightly different L4 larvae.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 923, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ffa4eb69-fde0-4c70-a482-5aa1098aad1b": {"__data__": {"id_": "ffa4eb69-fde0-4c70-a482-5aa1098aad1b", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.5, para 6](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6218ba77-d557-465b-978a-d2ce11de2d89", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.5, para 6](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "1d690dce13198ac40c50d6f4f0c1712dc8eda1a72c0e33eb3aa155ab6af499e8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## C. elegans Genetics", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 22, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e97a7f80-9171-4891-8c29-6b313a269e30": {"__data__": {"id_": "e97a7f80-9171-4891-8c29-6b313a269e30", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.5, para 7](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d478d399-0306-461d-b79e-052ed7fb2f0b", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.5, para 7](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "1981eb8167ebf6b26df880021031842e24cd0ede2fcc135bf5d738849d6e1330", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "A major reason Brenner (1974) chose to study *C. elegans* was the ease of genetic manipulation. Self-fertilization means that after hermaphrodites (P0s) are mutagenized, any mutant alleles (except dominant lethals) can be maintained through self-propagation in first-generation (F1) progeny, and second-generation (F2) progeny, etc. without mating. This property makes obtaining these progeny easy. In practice, *C. elegans* researchers screen for mutations anywhere in the genome (instead of using balanced strains to mutagenize single chromosomes) in a single mutagenesis and determine linkage afterward. A second genetic advantage of *C. elegans* is that it grows quickly. Since animals take \\~3 days at 25\u00b0 (\\~3.5", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 717, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "874cfdd2-3a56-491b-b986-b5c74cbf00ab": {"__data__": {"id_": "874cfdd2-3a56-491b-b986-b5c74cbf00ab", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.6, para 0](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2c39d670-c49a-4a44-a203-c91004bdef68", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.6, para 0](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "cab071a7beb3ee20fc2d39fe4223ed124875e2a794e46006d8ed6f91713612e1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Box 1. C. elegans Nomenclature", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 32, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ca091a28-cca1-4d23-ae80-e71dd1461a6c": {"__data__": {"id_": "ca091a28-cca1-4d23-ae80-e71dd1461a6c", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.6, para 1](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "596ea05c-21a8-4276-8f29-045cc8ec58e1", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.6, para 1](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "d82e66821bd8ce6d3f15eb31a44176089b0ea9bcf081b158dfa3ebdc50fcb5d2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Genetic nomenclature differs from species to species. Here, we describe the major terms used in *C. elegans* research. A more complete description can be found at", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 162, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "21a424d6-4e46-404c-bcb5-879926b72ca5": {"__data__": {"id_": "21a424d6-4e46-404c-bcb5-879926b72ca5", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.6, para 2](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "957fc21d-64be-4653-ae93-94b28aa07c06", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.6, para 2](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "bb60f7bdc77ef48dc1a7f97ab36d408c69eada983dc8f01de81e2dbbf11168e8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "[www.wormbase.org/about/userguide/nomenclature](http://www.wormbase.org/about/userguide/nomenclature)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 101, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c89bff2a-43c7-4790-bcb2-cf8db331d464": {"__data__": {"id_": "c89bff2a-43c7-4790-bcb2-cf8db331d464", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.6, para 3](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fcaf6cf7-407c-4d4b-aeac-a3fbf45c2f78", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.6, para 3](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "714158fe783cc809790069a5cdacc04b18c194d86d8cf17d1f10e235dfefdc20", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ".", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f458aa73-bc54-4408-8dc9-56a01d0450b8": {"__data__": {"id_": "f458aa73-bc54-4408-8dc9-56a01d0450b8", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.6, para 4](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "26dc4fa3-8a59-4198-94e4-1733c6d02982", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.6, para 4](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "c20e958e6aee432aa5ea692d90bdc06537df8d8ed5f537b2721c25b6c21d579f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Nomenclature at a glance^1:", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 30, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "21c24554-84c6-46de-99e4-5e6996946418": {"__data__": {"id_": "21c24554-84c6-46de-99e4-5e6996946418", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.6, para 5](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "097ff285-f2ac-4386-b092-eae42f709d75", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.6, para 5](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "220147106b42fe0cae13a534b6301471c36a30b1d0f77e587053b6c6121a6fe6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Term|Definition|\n|-|-|\n|ZK154.3|Systematic gene identification (3\\^rd\\ predicted gene on cosmid ZK154)|\n|\\*mec-7\\*|Gene name (the 7\\^th\\ \"mechanosensory abnormality\" gene named)|\n|\\*mec-7(e1506)\\*|Allele name (from the MRC Laboratory of Molecular Biology - e)|\n|MEC-7|Protein name (product of \\*mec-7\\* gene)|\n|Mec|Phenotype (Mechanosensory abnormal phenotype)|\n|e1506|Homozygous allele|\n|e1506/+|Heterozygous allele|\n|\\*mnDp30\\*|Duplication (from the Herman Lab - \\*mn\\*)|\n|\\*nDf6\\*|Deficiency/Deletion (from the Horvitz Lab - \\*n\\*)|\n|\\*muIs35\\*|Integrated transgene (from the Kenyon Lab - \\*mu\\*)|\n|\\*evEx1\\*|Extrachromosomal transgene array (from the Culotti Lab - \\*ev\\*)|\n|CB3270|Strain name (from MRC Laboratory of Molecular Biology - CB)|\n|\\*mec-7p::gfp\\*|GFP transcriptional fusion (using only the promoter of the gene)|\n|\\*mec-7::gfp\\*|GFP translational fusion (in which \\*gfp\\* is inserted in the coding sequence of the gene)|\n|\\*ceh-6(pk33::Tc1)\\*|Transposon (Tc1) insertion in \\*ceh-6\\* gene|\n^1 All *C. elegans* gene names, allele designations, and reporter genes are written in italics. Cosmids, proteins, phenotypes, and strain names are not written in italics.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1178, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "68bd1380-8f47-4c1b-8828-642deae7c215": {"__data__": {"id_": "68bd1380-8f47-4c1b-8828-642deae7c215", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.6, para 6](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "18234c41-03e7-4246-9593-2d5cdda1c397", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.6, para 6](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "7e6ac6e0411c14814612a4ba4bf80ffe3700a15589c4d5db2ba87473f95b8afd", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Mutation (allele) names:", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 28, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "de83565b-2d0a-4163-a777-8a88fce6f2b3": {"__data__": {"id_": "de83565b-2d0a-4163-a777-8a88fce6f2b3", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.6, para 7](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "41accb8e-6dbd-40d9-82fa-3fe62a4cdd3e", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.6, para 7](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "b2264db63c9bf17bbc8259d806e63f3002bda0256ab8c125dc047dab939a8305", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The wild-type allele of any gene is designated by an italicized plus sign, +. Mutant alleles are represented by 1-3 lowercase letters, which indicate specific laboratories, followed by a number. All gene and allele symbols are italicized, e.g., *unc-54*, *e678*, and *mn5*. The homozygous genotype is represented by a single copy of the allele name (*e678*). A heterozygous condition is indicated with a slash, e.g., *e364/+*, *e364/e1099*. Chromosomal abnormalities are indicated by one or two letters after the lab code, e.g., *mnDp30* is a duplication, *nDf6* is a deletion (called a deficiency), and *szT1* is a translocation. One or two letters may be added after the allele name to indicate particular properties conveyed by the mutation e.g. temperature-sensitivity (ts), amber (am), revertant (r), dominant (d), and semidominant (sd). When a gene has more than one mutation, such as could result from the intragenic reversion of a mutant allele, both the old and new mutations are indicated, e.g., intragenic reversion of *e1498* could yield *e1498u124r*.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1063, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "462ecff2-9643-434f-bf17-e904710a71d9": {"__data__": {"id_": "462ecff2-9643-434f-bf17-e904710a71d9", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.6, para 8](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8ecbe0c4-81d4-4931-b6e1-85c9bb5af8b5", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.6, para 8](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "23f888cf4f082cc8a0c92ba9e7d27a24d903bdc476b0977df6729c103065913a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Gene names:", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 15, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8869ee8a-fd66-4d75-b7e2-756e60615619": {"__data__": {"id_": "8869ee8a-fd66-4d75-b7e2-756e60615619", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.6, para 9](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7dabdbec-c43b-480e-bbf9-b9321f22dfa7", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.6, para 9](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "bf963379dd7bec3237616f3dc891b72626400e32a901fa55b0a73df5c7060952", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Genes are designated by 3 or 4 lower case letters, a dash, and a number (all italicized), e.g. *lon-2* and *ensh-1*. To distinguish alleles of the same gene, the allele names are placed in parentheses with no space between the gene and allele name, e.g., *mec-7(e1343)* and *mec-7(e1506)*. Genes that have been identified as an open reading frame (ORF) through bioinformatics approaches get a systematic gene identification (e.g. ZK154.3) until subsequent studies prompts them to be given a gene name. The upstream promoter region of a gene is indicated by the gene name followed by a \u201cp.\u201d The promoter and the protein-coding names are separated by two colons as are parts of fusion proteins. Thus, a gene encoding a MEC-7::GFP translational fusion driven from the *mec-7* promoter would be *mec-7::gfp*, whereas a *mab-5* transcriptional fusion would be *mab-5p::gfp*. A transposon insertion into a gene is similarly shown using the transposon name and two colons, e.g., *unc-22::Tc1* \\[most *C. elegans* transposons are labeled Tc (transposon, *Caenorhabditis*) and a number].", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1078, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fe85be3b-1be5-400c-bb2c-35a1dd7487e9": {"__data__": {"id_": "fe85be3b-1be5-400c-bb2c-35a1dd7487e9", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.6, para 10](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0ee7d42f-02e8-4d2b-9f74-fe75638dc27f", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.6, para 10](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "d3f6e09ef143bf31857323f00a4b75248162fd40de1f90b92375ac6e761029dc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Phenotypes:", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 15, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "11a26fc8-3a5d-4dcc-aabd-2133a2b62d8d": {"__data__": {"id_": "11a26fc8-3a5d-4dcc-aabd-2133a2b62d8d", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.6, para 11](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "15f524d6-a038-44b9-b548-5bda2fa4a2de", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.6, para 11](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "85c10a73d08117ea9368fb3a3109ecd6d81b8375b11f4de555bdf64916700dbe", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Mutant phenotypes are designated by the non-italicized gene name without the dash and number and with the first letter capitalized, e.g., Unc or Sma animals are Uncoordinated or Small in body size.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 197, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "394aa85a-40ca-427e-b056-8ee2f37e64e2": {"__data__": {"id_": "394aa85a-40ca-427e-b056-8ee2f37e64e2", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.6, para 12](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d5c85f54-507c-477d-87e6-c558089ba07d", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.6, para 12](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "6adc10bea6871f54f6176f5f0ead93a541ef15070d854282b51c0fc1287e3ed1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Gene products:", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 18, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fccdaf0e-77e0-47b8-a2d5-5a1753357f85": {"__data__": {"id_": "fccdaf0e-77e0-47b8-a2d5-5a1753357f85", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.6, para 13](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1d90d4d2-e762-4bb1-9476-6f2dc39e8556", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.6, para 13](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "faf111b8056432656ac09d5be76f88baebea372ff3d73baccee6c7e5ab9cd008", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RNAs are designated by the italicized gene name; proteins are designated by the gene name in all caps and not italicized (MEC-7). Sometimes specific amino acid changes are indicated.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 182, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f4bfe57d-0c6a-4b94-b2fe-3294279d4f9a": {"__data__": {"id_": "f4bfe57d-0c6a-4b94-b2fe-3294279d4f9a", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.6, para 14](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0cd8d53f-9bdb-4d65-b62a-0b399c24c4ff", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.6, para 14](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "96b3ef5d9753a17f77b24ced281c6fc86ff813dffb6edaf422726125b5b613cd", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Strain names:", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 17, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ea65e55e-a476-4097-a951-21bca1d4521f": {"__data__": {"id_": "ea65e55e-a476-4097-a951-21bca1d4521f", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.6, para 15](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b13c9188-7f4b-4a80-8d54-3b781a62e8f7", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.6, para 15](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "156b53b2c4c81c42ba9101fbb4bec65b8b8235eb301edd336a1cfcb6f5aa0c58", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Two capital letters and a number, e.g. CB429 and TU38, designate a strain containing one or more genetic differences. The letters indicate the laboratory that constructed the strain (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 183, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1671fda4-e89a-4d4f-ab4e-510acd987dd3": {"__data__": {"id_": "1671fda4-e89a-4d4f-ab4e-510acd987dd3", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.6, para 16](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5cb1cbbf-5f68-4aff-9322-0120c8d1480d", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.6, para 16](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "b1d079785f0e806a3c5d030d22714fc11688ecb9042fb9730201a46606a8064e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "). None of these symbols are italicized. Because a given strain can carry more than one mutation, strain names can be thought of as shorthand to describe animals carrying complicated genotypes. Genes (and/or alleles) in strains with several mutations are listed in chromosome and then map order with genes on the same chromosome separated by spaces and genes on different chromosomes separated by semi-colons. The italicized name of the chromosome can also be included, e.g., *lon-2* (*e678*) *mec-7(e1506)* X, *unc-54*; *myo-3*, and *e364*; *e66*; *u38/szT1*. *szT1* is one of many balancer chromosomes that are often used to maintain mutations that are lethal as homozygotes but viable as heterozygotes. For strains that contain reporter genes, there are two typical designations. The reporters are named for specific laboratories similar to mutant alleles, and they are further named according to whether the reporter gene is maintained extrachromosomally on a multicopy array using an \u201cEx\u201d label (e.g. *evEx1*) or is maintained by integrating the sequence (in most cases randomly) into the genome using an \u201cIs\u201d label (e.g. *muIs35*).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1137, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f1ab1fcd-3c23-4138-a29d-35e83fbaada8": {"__data__": {"id_": "f1ab1fcd-3c23-4138-a29d-35e83fbaada8", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.7, para 0](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ccb630ba-2a2b-4cf0-bc5b-a4950f36fb08", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.7, para 0](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "92a0e4694691e2f288e617b7b1a7e74e9b85794aa7d80fd289bab3b6fcdee39e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "days at 20\u00b0) to develop from fertilized eggs to adults producing their own fertilized eggs, mutant homozygotes can be detected two generations (\\~1 week) after mutagenesis. In addition, the ability to freeze and recover *C. elegans* makes it possible to preserve mutant strains without worrying that they have acquired unwanted suppressors, other modifiers, or additional background mutations or have lost important mutations, particularly if they are maintained as heterozygotes. Therefore, much less effort needs to be devoted to strain maintenance.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 551, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "eb2d8250-8a82-4c9c-8086-0562e586018a": {"__data__": {"id_": "eb2d8250-8a82-4c9c-8086-0562e586018a", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.7, para 1](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cc452023-0dc5-476f-97f3-209ac0c32760", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.7, para 1](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "a51a9130df5239f71e93b829994ce8719b0e7e408359b0d22f47d9594e00d504", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The traditional use of genetics in *C. elegans* (often referred to as \u201cforward genetics\u201d) begins with a screen or selection to find mutants with a particular phenotype followed by inference of the wild-type role of the gene from the nature of the mutant phenotype. Jorgensen and Mango (2002) have reviewed the many types of screens and selections used in *C. elegans* to identify mutations resulting in novel phenotypes (including conditional phenotypes) and mutations that modify (either enhancing or suppressing) existing phenotypes. A variety of mutagens have been used (Kutscher and Shaham 2014), including ethane methylsulfonate (EMS), an alkylating reagent that causes principally GC-to-AT transition mutations and small deletions, used by Brenner in his initial studies (Brenner 1974).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 792, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "de021e03-00f8-4a23-a6d2-a461ac1c09d7": {"__data__": {"id_": "de021e03-00f8-4a23-a6d2-a461ac1c09d7", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.7, para 2](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "04e0b802-0820-4e5b-8eee-aeeb485152c3", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.7, para 2](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "989861de3a35f5cb5d37e784ae76a05b69e6d87696aa48f32687f5225901d4c9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Once mutant strains have been obtained and shown to be true-breeding, *i.e.*, give mutant individuals in the next generation, they can be mapped using classical genetic tools (Brenner 1974). Originally, mapping involved linkage crosses to identify the chromosome containing the mutation followed by multiple three-factor crosses to refine its map position. Once a map position had been determined, the mutated gene could be identified molecularly (using the physical map of overlapping genomic clones) by transformation rescue of the mutant phenotype by the wild-type gene (Evans 2006; Merritt *et al.* 2010; Schweinsberg and Grant 2013). Transformation requires injection of DNA into the syncytial (multinucleated) gonad, where it is incorporated into the nucleus of some developing gametes (Mello and Fire 1995). Transposon-tagged mutations were also used to isolate the DNA of the mutated gene, allowing for its molecular identification (e.g., Greenwald 1985). The entire process of cloning a gene could easily take a year.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1026, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c4ea0dda-3376-4957-84c0-aed05d6740ba": {"__data__": {"id_": "c4ea0dda-3376-4957-84c0-aed05d6740ba", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.7, para 3](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "31c3aa2b-c108-41e4-ab1f-42f87cda261a", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.7, para 3](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "c110f35bb84a2b5e21e5fc040093080935b3564420ce5ec2cb5de26c2f115a89", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Today, however, the process of connecting a mutant phenotype to a gene is much more rapid due to advances in whole-genome sequencing (Doitsidou *et al.* 2010; Zuryn *et al.* 2010; Minevich *et al.* 2012). Mutants derived from the standard wild-type strain (called N2) are crossed to a wild-type strain obtained in Hawaii (CB4856), whose sequence differs from N2 at many positions \\[one single nucleotide polymorphism (SNP) per 91 \u00b1 56 kb; Swan *et al.* 2002]. Mutants reisolated after the cross have retained N2 sequences in the vicinity of the mutation, whereas N2 and Hawaiian sequences randomly segregate at other loci. Whole-genome sequencing can reveal the location of N2 DNA and lead, hopefully, to a small number of candidate genes that can be tested as above. This process can be done in a number of weeks and, as before, transformation rescue (or complementation testing) provides evidence that the correct gene has been identified.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 941, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1ad20833-3fa8-44a5-9fcd-7bd1141f95d8": {"__data__": {"id_": "1ad20833-3fa8-44a5-9fcd-7bd1141f95d8", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.7, para 4](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f31ed71c-06f5-4e3e-9a2a-85800f4d8e7b", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.7, para 4](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "6f1f914e7511e6cf3662ed619a9ec8cfd0a66002df240dbedf3b91d080251fb3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Researchers can also use a known gene sequence to obtain mutant strains, a process called \u201creverse genetics\u201d (Ahringer 2006). One of the first ways to do such reverse genetics was the generation of strains that deleted all or part of a target gene (Lesa 2006). Animals were mutagenized with trimethylpsoralen to cause deletions and large numbers of individual F2 animals were used to establish lines. Pooling DNA from these strains and amplifying the several pools of DNA with PCR primers, designed to amplify a deleted but not wild-type gene, could identify which line had a deletion mutation (a process called sibling selection). Further selection within the line could establish a homozygous strain containing the deletion mutation.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 735, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f1481288-7069-4a0c-a4bd-7a5af60d69df": {"__data__": {"id_": "f1481288-7069-4a0c-a4bd-7a5af60d69df", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.7, para 5](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "765c2755-e892-468d-bfae-a8004e1cf87b", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.7, para 5](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "b88ec6cb2921bf478d95fbbb9c20036db20d99a4bdfc92407cacf8672c527e39", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Whole-genome sequencing has enabled a very rapid way of obtaining mutations. In a study dubbed the \u201cmillion mutation project\u201d (Thompson *et al.* 2013), animals were mutated by EMS and/or N-ethyl-N-nitrosourea (ENU) and F2 progeny (from different P0 parents) were grown. Over 2000 healthy strains were established from these mutageneses. Whole-genome sequencing of each strain showed that, on average, there were 400 mutations per strain. Altogether these strains had over 800,000 unique mutations. Since the genome contains \\~20,000 genes, each gene has been mutated an average of eight times. The results are available in WormBase and the strains can be obtained from the *Caenorhabditis* Genetics Center (Table 1). Recent advances in efficient genome-editing methods (TALEN and CRISPR/Cas9) in *C. elegans* now allow investigators to create targeted mutations in nearly any location in the genome in any genetic background (Fr\u00f8kj\u00e6r-Jensen 2013; Waaijers and Boxem 2014). These gene editing techniques, particularly CRISPR/Cas9, enable rapid methods to mutate and interrogate *C. elegans* genes, and new approaches based on them are being introduced.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1151, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c8e2194e-7542-4707-a348-17895ad28d12": {"__data__": {"id_": "c8e2194e-7542-4707-a348-17895ad28d12", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.7, para 6](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2886430a-487d-41ce-ad37-72d80b884bad", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.7, para 6](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "596e5f84b4d8f7ce85b3c0176effa042661c3aa35999b1322339e4b9b8466a76", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Mutant-like phenotypes can also be obtained using RNA interference (RNAi), the use of double-stranded RNA (dsRNA) to reduce gene activity (Fire *et al.* 1998, see Ahringer 2006). The added discovery that RNAi can be produced by soaking the animals in a solution of dsRNA (Tabara *et al.* 1998) or by feeding the animals bacteria that generate specific dsRNA (Timmons and Fire 1998) means the entire genome can be easily and systematically interrogated for genes needed for specific functions. Such genome-wide screens using libraries of bacterial strains are common and easily done.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 582, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b576a7bf-54bd-4695-9c59-eb2af41aa4d0": {"__data__": {"id_": "b576a7bf-54bd-4695-9c59-eb2af41aa4d0", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.7, para 7](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fac6433f-8082-4984-b667-54421bd60dc0", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.7, para 7](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "f4dbb6eedcb013fab0d829df2e78d8db06d884f77564168fb65da3a45567f227", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Why Choose *C. elegans*?", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 27, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "997c9c13-1ef6-41a8-9b55-07670e6ef7b4": {"__data__": {"id_": "997c9c13-1ef6-41a8-9b55-07670e6ef7b4", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.7, para 8](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5510b72d-ec70-467b-93c8-e9eb804683c6", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.7, para 8](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "b050a065b9961589a9406390795173fc75637ad9daf5fa856b225dc2589bdbd3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In addition to being a powerful system for genetic studies, *C. elegans* has many inherent advantages as a model for eukaryotic biology. These features include its small size, large brood size, ease of cultivation, low maintenance expense, long-term cryopreservation, quick generation time,", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 290, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4a028711-e0e5-4f97-bdc1-6d2fbadeec58": {"__data__": {"id_": "4a028711-e0e5-4f97-bdc1-6d2fbadeec58", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.8, para 1](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e3bbaf1d-a686-4939-bd51-be352a467139", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.8, para 1](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "c65348f981929a11ddc685f3b3f7200fefe1d97520cd932138f6cd6bc005a7e2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Resource|Website Address|Description|\n|-|-|-|\n|WormBase|http://www\\.wormbase.org/|Genes, expression, resources, phenotypes, metadata, and publications|\n|WormBook|http://www\\.wormbook.org/|Basic information about the biology of \\*C. elegans\\* and other nematodes, including methods|\n|WormAtlas|http://www\\.wormatlas.org/|Worm anatomy, including neurons and wiring, EM sections, and cell lineage|\n|Caenorhabditis Genetics Center|https://www\\.cbs.umn.edu/research/resources/cgc|Stocks of wild-type and mutant nematode strains|\n|National Bioresource Project|http://www\\.shigen.nig.ac.jp/c.elegans/index.jsp|Collection of deletions of \\*C. elegans\\* genes|\n|Million Mutation Project|http://genome.sfu.ca/mmp/|Fully sequenced genomes of strains carrying multiple mutations|\n|Expression patterns database|http://gfpweb.aecom.yu.edu/index|Expression patterns for promoter::gfp transgenes|\n|TransgeneOme|https://transgeneome.mpi-cbg.de/transgeneomics/index.html|Resource for tagged gene constructs and expression patterns|\n|modENCODE|http://www\\.modencode.org|Model organism database of DNA elements|\n|UCSC Genome Browser|https://genome.ucsc.edu/|Multiple alignments of conserved nematode genome sequences|\n|C. elegans Interactive Network|http://www\\.wormweb.org/|Interactive neuron wiring diagram and gene expression information with direct links to published supporting data|\n|OpenWorm Science|http://www\\.openworm.org/|Various on-line resources for \\*C. elegans\\* research.|\n|C. elegans Behavioral Database|http://wormbehavior.mrc-lmb.cam.ac.uk/|Detailed traces of worm movement and posture for different strains and mutants|\n|Caenorhabditis briggsae|http://www\\.briggsae.org/|Resource for research on \\*C. briggsae\\*|\n|Research Resource|||\n|Nematode and Neglected Genomics|http://www\\.nematodes.org/|Database of genomics for other nematode species|\n|Rhabditina Taxonomy|http://128.122.60.136/fmi/iwp/cgi?-db=RhabditinaDB&-loadframes or http://wormtails.bio.nyu.edu/Databases.html|Nematode phylogeny, morphology, literature, ecology, and geographical information|\n|WormClassroom|http://wormclassroom.org/|Resource for education using \\*C. elegans\\*|\ntransparency, invariant cell number and development, and the ability to reduce gene activity using feeding RNAi. Although not usually mentioned, another favorable feature of *C. elegans* is the organisms are quite benign to humans. In fact, because they cannot grow at body temperature, they cannot grow in humans. Some nematodes, e.g., *Ascaris suum*, induce a debilitating allergic reaction and must be studied in ventilated hoods (Kennedy 2013; A. O. Stretton, personal communication). As far as we are aware, allergic reactions to *C. elegans* have not been documented.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2718, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4b2e2aeb-d8dc-4ab8-9dd8-892fdc932b29": {"__data__": {"id_": "4b2e2aeb-d8dc-4ab8-9dd8-892fdc932b29", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.8, para 2](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7e797384-ac9d-460b-95b5-1e8c38087e82", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.8, para 2](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "25c63ebe4fda5aa97f749a3fe14d69b5219366f12d13d53ae7e986c3cd96fdf7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Studies of cell and developmental biology that use *C. elegans* are greatly aided by the transparency of the animal, which allows researchers to examine development and changes due to mutations or altered environments at the level of a single, identified cell within the context of the entire living organism. Thus, many biological problems can be studied \u201cin miniature\u201d at the single-cell level, instead of in large numbers of cells in heterogeneous tissues. Transparency also enables a wealth of studies in living animals utilizing fluorescent protein reporters (Figure 1D and Figure 4B). By labeling cells and proteins in living cells, fluorescent proteins enable genetic screens to identify mutants defective in various cellular processes. In addition, fluorescent protein-based reporters (e.g., Cameleon and gCaMP3; Figure 4C), which fluoresce in response to calcium flux, provide neuron-specific detection of calcium flux under a fluorescent microscope and therefore allow researchers to measure electro- physiological activity *in vivo* (Kerr 2006). Furthermore, mapping of cell\u2013cell and synaptic contacts can be accomplished by expressing complementary fragments of GFP in different cells (GRASP; Feinberg *et al.* 2008). Transparency also means that optogenetic tools, which alter the activity of individual neurons, are particularly effective in *C. elegans* (Husson *et al.* 2013). In all of these experiments, greater control of the animal\u2019s position and environment can be accomplished by microfluidic devices in which individual worms are mounted in custom-designed channels allowing the application of various compounds or other agents while simultaneously monitoring fluorescent read-out of gene regulation or electrophysiological activity by microscopy (Lockery 2007; San-Miguel and Lu 2013).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1809, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "19d88b08-25fb-4b18-b4f0-7e1ce47238cf": {"__data__": {"id_": "19d88b08-25fb-4b18-b4f0-7e1ce47238cf", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.8, para 3](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e5197afe-d4d0-4c35-87fa-491b374ff841", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.8, para 3](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "2424acb565e6e8681001f6e728117a8b5eefdd656e7c64fe8c36e9aa17eefae2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sharing large amounts of genetic and cellular information has been central to the success of *C. elegans* research. The wealth of knowledge generated by past research is readily available to anyone via on-line resources (see Table 1). Much of this information, including gene expression, gene function, and references, is curated on WormBase (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 343, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d388887e-4b73-4d3b-8fea-11056eaacdee": {"__data__": {"id_": "d388887e-4b73-4d3b-8fea-11056eaacdee", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.8, para 5](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f8212596-0bcf-4acf-ad96-2aa076587633", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.8, para 5](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "cbe2474f00704a44e9371357aee7f63d2d513726a416996d4fb57f69b7e5e725", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "). Reviews on many topics of *C. elegans* biology are provided by WormBook (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 76, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "66f6c082-f8b8-4a74-9231-57cb6bd13b55": {"__data__": {"id_": "66f6c082-f8b8-4a74-9231-57cb6bd13b55", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.8, para 7](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0e74db7b-65f4-4785-9ab0-9708828e411e", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.8, para 7](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "2997cb04eecbd4d6508b472fb252df4afede8d78832002399e0d29ce41581b8a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "), which includes a collection of *C. elegans* methods (Worm-Methods) and current and past issues of the *C. elegans* Newsletter (The Worm Breeder\u2019s Gazette).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 158, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "547d3549-d826-4f9b-9b85-2555f594ad18": {"__data__": {"id_": "547d3549-d826-4f9b-9b85-2555f594ad18", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.8, para 8](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e45c4b65-eaab-491a-8a50-6aa3c99e3b72", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.8, para 8](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "a1b08923c17027072517eab82fd5b6b352a806a83855ea2326e1c42632b45da5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "No model organism can be used to answer every research question, and working with *C. elegans* has some limitations. Not all metazoan genes are found in the *C. elegans* genome", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 176, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0f506519-fe5b-4e48-9be8-ca6a5101567d": {"__data__": {"id_": "0f506519-fe5b-4e48-9be8-ca6a5101567d", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.9, para 0](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "60a0f0b1-0569-4fae-8a6e-e8c0714e9ac2", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.9, para 0](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "4f7d19cdc0dad72da65e7fd38cbabc37227b751cb1290ed0425530eef79cf7d5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Figure 4 Anatomy and study of the *C. elegans* nervous system. (A) Diagram of the *C. elegans* nervous system identifying some major nerve bundles and ganglia. Major nerve tracts include the ventral nerve cord (VNC), dorsal nerve cord (DNC), and nerve ring. Major ganglia include the ring ganglia, retrovesicular ganglion (RVG), preanal ganglion (PAG), and dorsal-root ganglion (DRG). Image was produced using the OpenWorm browser utility (openworm.org). (B) Visualization of anterior sensory neurons and their neurite projections by expression of a GFP reporter transgene. The Y105E8A.5::GFP fusion transgene is expressed in amphid, OL, and IL sensory neurons of the head (R. Newbury and D. Moerman, Wormatlas; wormatlas.org). (C) Use of cameleon reporter transgene to detect calcium transients in the *C. elegans* pharynx. The animal carries a transgene with *myo-2*, a pharynx-specific myosin gene, fused to YC2.1, a calcium-sensitive fluorescent detector. False-color red in the pharyngeal bulb reflects real-time calcium releases in the cell of the living animal. Image was adapted from Kerr *et al.* (2000). (D) Electron microscopic section showing synapses. Collections of densely staining vesicles can be seen in neuron 1 at the point of synaptic connection to neurons 2 and 3 (arrows). Synaptic varicosities (V) that contain vesicles can be seen clustered around the active zone. DCV identifies a dense-core vesicle. Image is from D. Hall (Wormatlas; wormatlas.org). (E) Worm behavior on a bacterial plate. Left image shows the standard laboratory N2 strain foraging as individuals evenly dispersed across the bacterial food. Right image shows an *npr-1* mutant strain foraging in grouped masses (sometimes called a \u201csocial\u201d feeding phenotype). Image is from M. de Bono, taken from Schafer (2005).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1806, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "64a5dcd2-7e15-4f73-837d-6c1306eeffe5": {"__data__": {"id_": "64a5dcd2-7e15-4f73-837d-6c1306eeffe5", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.9, para 1](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3ab3866b-3ded-44a3-b545-3c707002ba20", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.9, para 1](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "82ccff77aa2ff52c762aaf7ec8cc652b3b4de99c26279deae383f83ec6639055", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "(Ruvkun and Hobert 1998). For example, Hedgehog (Hh) signaling is important in vertebrates for the patterning of various organs during development, but *C. elegans* lacks many of the genes in the regulatory cascade (B\u00fcrglin and Kuwabara 2006). Although some *C. elegans* cells can be studied *in vitro* \\[e.g., embryonic glial cells, larval muscle, and neuronal cells (Zhang *et al.* 2011; Stout and Parpura 2012)], no *C. elegans* cell culture lines exist. The small size of the animal and its cells also provides a challenge, since experimental manipulation in individual tissues of an organism that is less than a millimeter long is difficult. Electrophysiology of *C. elegans* neurons and muscle is possible, but demanding (Raizen and Avery 1994; Lockery and Goodman 1998; Cook *et al.* 2006; Richmond 2006) and indirect measurements of neuronal activity, such as calcium imaging are often used instead (Kerr 2006). Finally, biochemical approaches in *C. elegans* have lagged behind the genetic approaches, but the development of an axenic culture medium for *C. elegans* (e.g., Rao *et al.* 2005) has meant that biochemical studies can be done on animals under defined conditions.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1185, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "541547ac-0a0d-4560-a0bf-75621a255445": {"__data__": {"id_": "541547ac-0a0d-4560-a0bf-75621a255445", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.9, para 2](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ae9c7631-19e6-4da0-80c3-0728bd89cf52", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.9, para 2](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "eb42cfd788af50b5c1a2ee23ccd8038f4f99cd7574d6142bd86ec2d23a300763", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### *C. elegans* Tissues", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 24, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8bc64966-30f1-451d-907d-ccb1c8958eb8": {"__data__": {"id_": "8bc64966-30f1-451d-907d-ccb1c8958eb8", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.9, para 3](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ca0fc613-2dc7-466d-bca9-c5a36ee16945", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.9, para 3](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "89acfc9dd9d3bef8fc6048ddd083a073a9937d736cc998b0bbebb4523aaf48b1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "One attractive feature of *C. elegans* is that despite its simplicity, it has defined tissues. The animal is often described as a series of concentric tubes (Figure 3C). The outer layer of cells, the epidermis (traditionally called the hypodermis) encloses a pseudocoelomic fluid-filled cavity housing the main organ systems. Just inside the epidermis are the bands of muscle, which control movement of the organism, as well as the ventral and dorsal nerve cords that innervate the muscles. Inside the neuromuscular region are the digestive, excretory, and reproductive systems. In addition, *C. elegans* has six cells in the pseudocoelomic cavity, called coelomocytes, which act as scavengers in the body cavity (Grant and Sato 2006). These cells behave similarly to vertebrate macrophages (although they have a fixed position within the animal), are highly active in endocytosis, and are thought to sort through and clear material in the pseudocoelomic cavity of the animal. More extensive descriptions of these systems with beautiful electron micrographs of the various cell types can be found in WormAtlas (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1111, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d8fb8137-aa2d-42c7-94a2-97e8a6895223": {"__data__": {"id_": "d8fb8137-aa2d-42c7-94a2-97e8a6895223", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.9, para 5](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "44b1cb50-9de4-4da4-876a-f0f40d282546", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.9, para 5](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "3f183a97f0a79072861703d00ce7420e4fc03f3b7d49cf9525797a1d03d5afd6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "). Here, we will cover some of the basic aspects of the anatomy, particularly with respect to how the organ systems are advancing the understanding of cell and developmental biology.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 182, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4ec37e02-ad45-4e73-8841-f3986551c203": {"__data__": {"id_": "4ec37e02-ad45-4e73-8841-f3986551c203", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.9, para 6](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "49a66e82-2d16-496d-afb2-15f5f6cd4534", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.9, para 6](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "a2b23dd7888af2d43eee79c9fea1676d2e7b30cb79fafafc2b705acd4dec9e9d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "#### Epidermis: a model for extracellular matrix production, wound healing, and cell fusion", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 91, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "93af1181-ded0-4341-a2aa-bcc1e7a3b4f4": {"__data__": {"id_": "93af1181-ded0-4341-a2aa-bcc1e7a3b4f4", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.9, para 7](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4143aa4d-f182-408c-804a-c2d339d5f9c9", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.9, para 7](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "29fa689a693262057fa41103efde7ef9fb6faf4ef6bb0b32a94f7deb7ab72804", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The outer epithelial layer, the epidermis, of the embryo undergoes a series of cell fusions to make large multinucleate, or syncytial, epidermal cells. These cells secrete the cuticle, a protective layer of specialized extracellular matrix (ECM) consisting primarily of collagen, lipids, and glycoproteins (Chisholm and Hardin 2005; Page and Johnstone 2007). The cuticle determines the shape of the body and, through", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 416, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c479ebb6-2ef3-485c-8883-5c199fcb6985": {"__data__": {"id_": "c479ebb6-2ef3-485c-8883-5c199fcb6985", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.10, para 0](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7a93a0b0-b029-43a9-800c-c752922e3af6", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.10, para 0](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "cdcf9831eaaacef4ed32e66c666bc7bc5115d22bcc7d30a1063aeafeed26394b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "connection from the epidermis to muscle, provides anchoring points for muscle contraction (Figure 5A). The cuticle also serves as a model for ECM formation and function with molecules and pathways involved in cuticle biogenesis conserved in vertebrates (Page and Johnstone 2007).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 279, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6ffce76e-916e-435f-a9f5-ecc1a37534d8": {"__data__": {"id_": "6ffce76e-916e-435f-a9f5-ecc1a37534d8", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.10, para 1](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1008d648-e065-4606-a1f6-35455242e7e4", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.10, para 1](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "bb8ed5f35b30869851cb2cb4a3e97ef9c0bf4d94f90ce707b86f929f43611948", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Mutations in several genes needed for cuticle formation produce visible phenotypes (Figure 6). Mutations in collagen genes can result in animals that move in a cork-screw fashion \\[the Roller (Rol) phenotype] or that have normal width but reduced length \\[the Dumpy (Dpy) phenotype]. Other mutations affect the struts formed between layers of the adult cuticle, resulting in fluid-filled blisters \\[the Blister (Bli) phenotype]. Still other mutations make the animals longer than normal \\[the Long (Lon) phenotype]. At the end of each larval stage (Figure 2), *C. elegans* sheds its cuticle and secretes a new one to accommodate the growing organism. Genes involved in cuticle formation are regulated so that the cuticle is reestablished after each molt.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 754, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "91ecd3d2-8695-4973-aa93-3986f11160d3": {"__data__": {"id_": "91ecd3d2-8695-4973-aa93-3986f11160d3", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.10, para 2](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "daff6187-bd81-410e-b225-50ee7cabd387", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.10, para 2](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "e11ca98317ca35722c2a2da7c009cfff8990d6014b361442f1a1c39ffd15569e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Studying the epidermis has led to insights in early cell movements, wound healing, cell\u2013cell fusions, and the establishment of epithelial layers in developing embryos (Chisholm and Hardin 2005; Podbilewicz 2006). As the \u201cskin\u201d of *C. elegans*, the epidermis is a model for the innate immune response to pathogens and for repair after a physical wound such as a needle puncture. The wounded epidermis upregulates both Ca^++ signaling to direct actin polymerization for repair and innate immune signaling pathways to help promote survival after injury (Xu *et al.* 2012). The cell\u2013cell fusion events leading to the multinucleate epidermis and genes important for this process have been studied (Podbilewicz 2006). This work has supported the idea that repression of fusion in some cells may be just as important for proper development as activation of cell fusion in other cells (Podbilewicz 2006).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 896, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "60eaae71-aff3-4813-b8a3-31e7b0c0b718": {"__data__": {"id_": "60eaae71-aff3-4813-b8a3-31e7b0c0b718", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.10, para 3](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7c1b4ca0-473c-4970-bdb3-ce3e9772fddd", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.10, para 3](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "4d2bc7f776f62d7fc41ccbff51257225872d6a544f7b52e656cbb26ab5f6699f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Muscles\u2014controlling animal movement", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 38, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a7a0bf88-81d0-476c-b88c-56125fee0efc": {"__data__": {"id_": "a7a0bf88-81d0-476c-b88c-56125fee0efc", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.10, para 4](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3fb7d6e9-66da-4138-8a1c-03eae2b9391a", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.10, para 4](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "05d0dea62093c311d057349c43f044e9cfa72e49a3d9d5fe92170b67508e68de", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Just interior and connected to the epidermis are four quadrants (95 cells) of body-wall muscles that run along the length of the body (Figure 3). The regular contraction and relaxation of the muscle cells leads to the \u201celegant\u201d sinusoidal movement of the animal. These somatic muscles are striated (although, unusually, they are obliquely striated) and mononucleate (muscle cells do not fuse as they do in vertebrates) with multiple sarcomeres per cell (Moerman and Fire 1997). The innervation of these muscles is also unusual in that the muscle cells send extensions (\u201cmuscle arms\u201d) to the ventral and dorsal cord to receive en passant synapses from the motor neurons instead of the more usual case of receiving axonal projections from motor neurons (White *et al.* 1986; Figure 5D).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 784, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "154603ba-9060-4a12-b037-7570af4d8fd7": {"__data__": {"id_": "154603ba-9060-4a12-b037-7570af4d8fd7", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.10, para 5](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6c6cd3df-92f6-4deb-8647-92ecd97f81ea", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.10, para 5](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "ec083aa0957cc7045a3d40e9ff3f4ece58afe08457b03400e647215a5806d804", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Genetic studies of muscle led to the first cloning and sequencing of a myosin gene (*unc-54*; MacLeod *et al.* 1981), and this finding provided major insights into the structure of all myosins. *unc-54* and many other *unc* (uncoordinated) genes encoding proteins needed for muscle activity pro-", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 295, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "868bfac6-1989-48df-8ac9-fb679b8b01bd": {"__data__": {"id_": "868bfac6-1989-48df-8ac9-fb679b8b01bd", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.10, para 6](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a1893da6-4391-4488-b56b-2e8d9a46a33d", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.10, para 6](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "985ef62c51df0088e51deda2c8f229eb7846bd18610aaa046cc9361053696a3d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "duce a \u201cfloppy paralytic\u201d phenotype (Hodgkin 1983). The study of the assembly of sarcomeres into functional muscles and, in particular, the proteins mediating attachment to the plasma membrane has revealed many molecules in common with vertebrate focal adhesion complexes (Moerman and Williams 2006). Genetic screens designed to understand molecules involved in muscle contraction have also led to insights regarding muscle-wasting diseases such as Duchenne\u2019s muscular dystrophy (Chamberlain and Benian 2000) and cardiomyopathies (Benian and Epstein 2011). In addition to the body-wall muscles, *C. elegans* has muscles that control eating (pharyngeal muscles), egg laying (vulval and uterine muscles and the contractile gonad sheath), mating (male-specific tail muscles), and defecation (enteric muscles).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 806, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "790c563b-639e-4570-b1bb-4a6119e7a58c": {"__data__": {"id_": "790c563b-639e-4570-b1bb-4a6119e7a58c", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.10, para 7](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7c9fd3d3-0a4b-400c-9417-48e00e84925d", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.10, para 7](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "1264e9fc96d7cfa72bbfe2335067b605933bdd9eacecb387df527175f6750ec9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## The digestive system\u2014a model for organogenesis and pathogenesis", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 66, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "75666066-3988-4bd0-8d18-a6206e24fbc6": {"__data__": {"id_": "75666066-3988-4bd0-8d18-a6206e24fbc6", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.10, para 8](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "518d6087-ff1c-4ce2-84db-543eabf85b1b", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.10, para 8](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "d099fe3726063ee54b6cbd07bae7eeec5ec8e4045798d89d9ed8741c1c4df852", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Food (bacteria) enters the anterior of the animals and passes through the pharynx, a two-lobed neuromuscular pump that grinds the food before it is passed on to the intestine for digestion (Figure 5C; Avery and You 2012). The pumping behavior of the animals depends on the availability and the quality of the food; for example, animals pump more when hungry and less when full (Avery and Shtonda 2003). Studying pharyngeal development has been a model for organogenesis, including how epithelial morphogenesis and cell-fate specification occur during development (Mango 2007). For example, the transcription factor PHA-4 plays a major regulatory role in the organ identity of the pharynx (Mango *et al.* 1994). Animals defective in PHA-4 function do not contain a pharynx and embryos that overexpress PHA-4 have more pharyngeal cells (Mango 2007). The vertebrate FoxA transcription factors are homologous to PHA-4 and are involved in gut development in many species (Carlsson and Mahlapuu 2002).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 995, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3e5a2ffc-e4ce-4bd5-adab-bab190dfd0bf": {"__data__": {"id_": "3e5a2ffc-e4ce-4bd5-adab-bab190dfd0bf", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.10, para 9](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8eef5443-c458-4255-b3ed-c830fd3125b4", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.10, para 9](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "2cda2c6d7941e73fe07c5ab9a61a17ac081f2e779432770e2ad56a2652375495", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The *C. elegans* intestine is attached to the posterior pharynx and consists of 20 large, polyploid epithelial cells arranged in pairs that form a tube running the length of the animal. Intestinal development has been studied in detail (McGhee 2007). Presumably to handle the increasing demands of the growing animal, the intestinal cells undergo one round of nuclear division during the first larval stage and subsequent rounds of DNA replication, but not nuclear division, in the later larval stages (Hedgecock and White 1985). *C. elegans* has served as a model to study infection and response to infection by several different bacterial pathogens, microsporidia, and viruses that colonize the digestive system (Darby 2005; Balla and Troemel 2013; Diogo and Bratanich 2014).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 777, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ba1e226a-0ead-4f2b-afb1-7fc905cd359b": {"__data__": {"id_": "ba1e226a-0ead-4f2b-afb1-7fc905cd359b", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.10, para 10](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b064593a-4e3b-42ef-9330-fcc60d9ffc91", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.10, para 10](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "442195b9e570801a9d2faa4257119d70527e119db24d5196a12a1d23d4a52d3f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## The nervous system\u2014small yet complex", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 39, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "99eb1b45-f153-46a1-8785-b8572555f8f9": {"__data__": {"id_": "99eb1b45-f153-46a1-8785-b8572555f8f9", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.10, para 11](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "51f639c4-ab72-493c-8470-cb6453b8bf14", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.10, para 11](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "b29d1699c8fcb22acf4462f8424cbad3086d5e5edb2082bb8d9ad865f029ba29", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "*C. elegans* has become an important model for the study of neurobiological questions. Researchers have identified genes and mechanisms needed for neuronal generation and specification, cell death, precursor migration, synapse formation,", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 237, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4bd444b2-9707-4c01-89c3-f8ebb23a5607": {"__data__": {"id_": "4bd444b2-9707-4c01-89c3-f8ebb23a5607", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.11, para 0](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2000f007-6af1-4925-b7e0-b9a21ee17852", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.11, para 0](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "f761c830507aea3e162e33cf0b915e8da69267cda53c5b82fb5210af18a2d3e5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# C. elegans tissue morphology", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 30, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "afe6fa6a-bf48-47a8-ba8d-2ba6287c3fb6": {"__data__": {"id_": "afe6fa6a-bf48-47a8-ba8d-2ba6287c3fb6", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.11, para 1](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2d68e046-dfdb-463a-ba96-05c648f92f75", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.11, para 1](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "a146486adb3c251ccf291bc74c6ca6bfd8ba84385aa7643f2d277836038e56a5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Figure 5 C. elegans tissue morphology. (A) Cross-section of the outer layers of the animal showing muscle cells below the epidermis and cuticle viewed by transmission electron microscopy. (B) Single gonad arm dissected out of a hermaphrodite showing germ cell DNA (stained white). Meiosis begins in the region labeled \"pachytene\" (top right) and continues around the loop of the gonad until oocytes are formed. The stored sperm are located in the spermatheca of the gonad (bottom right). This image is a composite of three gonad arms and dashed lines represent regions not captured in the individual micrographs. (C) The anterior of the animal showing the mouth where food enters, the pharynx with its two bulbs, and the beginning of the intestine viewed with differential interference contrast (DIC). (D) A single body wall muscle cell with six muscle arms (marked with asterisks) extending to the ventral nerve cord (lateral view). The micrograph shows fluorescence from both muscle and neuronal GFP reporters \\[him-4p::MB::YFP (muscle), hmr-1b::DsRed2 (neuron), and unc-129nsp::DsRed2 (neuron)]. All images are modified from WormAtlas (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1139, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d8de01bc-00c4-4552-855b-ee313ebe15ec": {"__data__": {"id_": "d8de01bc-00c4-4552-855b-ee313ebe15ec", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.11, para 3](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "94747c06-24d5-44b6-baa7-bc560f501bd7", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.11, para 3](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "7109c53c908e6375aa6fd2f8714bc66b72eb5e7f106316f03c20b95f749b0597", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "). Photo credits: (A) D. Hall, (B) J. Maciejowski and E. J. Hubbard, and (C and D) WormAtlas.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 93, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3de4b2f8-b281-4e69-b413-2d9cfc93515a": {"__data__": {"id_": "3de4b2f8-b281-4e69-b413-2d9cfc93515a", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.11, para 4](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8b16bf54-13ca-46d9-a642-4936c2112dac", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.11, para 4](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "024bb624e6adb2edf15f1a81a7958df0e6dfc921d118b1d130ff4536ad876cc2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "chemosensory and mechanosensory transduction, neuronal degeneration, neurite regeneration, and glial function (Driscoll and Chalfie 1992; Silhankova and Korswagen 2007; Hammarlund and Jin 2014; Shaham 2015). Researchers also have investigated a variety of behaviors, both simple and complex, including chemotaxis, thermotaxis, several responses to touch, male-specific mating rituals, social feeding, and both associative and nonassociative learning (Bargmann 2006; Hart 2006; Barr and Garcia 2006; Ardiel and Rankin 2010; Figure 4E). C. elegans also experiences periods of restful inactivity that are similar to aspects of mammalian sleep (Raizen et al. 2008).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 661, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "49ec8168-36a1-4a89-989a-d8549832bbeb": {"__data__": {"id_": "49ec8168-36a1-4a89-989a-d8549832bbeb", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.11, para 5](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c5d07231-ec89-4836-bec7-17a1885fc0ca", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.11, para 5](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "56e3c2ae9007699bb62c429f1ff81da06854149001d22330a2caedc74c6b5f98", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The nervous system of the adult hermaphrodite has 302 neurons (Sulston and Horvitz 1977; White et al. 1986); that of the adult male has 383 neurons (Figure 4; WormAtlas.org). The majority of neuronal cell bodies are arranged in a few ganglia in the head, in the ventral cord, and in the tail (the specialized male tail has the majority of the extra neurons). Most of the neurons have a simple structure with one or two neurites (or processes) exiting from the cell body, but a few cells, such as the FLP and PVD mechanosensory neurons, have elaborately branched neurites (Dong et al. 2013). Except for sensory dendrites, which are often easy to identify, most neurites cannot be distinguished as axons or dendrites because they both give and receive synapses (although they are often referred to as \u201caxons\u201d). The neurites form synapses to each other in four major areas: the nerve ring (which encircles the pharynx), the ventral nerve cord, the dorsal nerve cord, and the neuropil of the tail. In addition to neurons, C. elegans has several glia-like support cells, which are primarily associated with sensory neurons, but are not as numerous as in vertebrates (Oikonomou and Shaham 2011).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1189, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5f0379b0-7706-4c58-9c89-8e2b434dee7e": {"__data__": {"id_": "5f0379b0-7706-4c58-9c89-8e2b434dee7e", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.11, para 6](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bff25476-2311-4543-94b2-c293a1440219", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.11, para 6](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "b37778da9ab44e4550c0eae8c3d87d09275bc8e6c04157320a2b78a50753cc86", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Nerve conduction in C. elegans appears to be primarily passive. No sodium-dependent action potentials have been detected in neurons (Goodman et al. 1998) and the genome has no genes for voltage-gated sodium channels (Bargmann 1998). The absence of action potentials may be due to the very high membrane resistance. Indeed, many neurons are essentially isopotential; changes in voltage are experienced virtually instantaneously by the entire cell (Goodman et al. 1998), so action potentials may not be necessary (Lockery and Goodman 2009). Neurons express a wide variety of ion channels (Hobert 2013), including an unexpectedly large number of genes encoding potassium channels (Salkoff et al. 2005).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 699, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9bf7d458-2de5-44d3-ae41-27cec3189b9e": {"__data__": {"id_": "9bf7d458-2de5-44d3-ae41-27cec3189b9e", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.11, para 7](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5d27a9ad-07ea-4fe9-ae17-dfccd01d3314", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.11, para 7](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "0ce84316c0ba02fed300cca04a037c6f9a581073f01ad2c6e8ea4d277296c51b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "C. elegans neurons make more than 7000 chemical synapses and gap junction connections (White et al. 1986). Unlike in vertebrate nervous systems, C. elegans neurons do not send terminal branches with boutons to make synapses. Most of the connections are made en passant (side by side as neurites pass each other), although many bilaterally symmetrical neurons join their tips together with gap junctions at the midline and some motor neurons similarly join with homologs end to end. Nematodes are unusual in that motor neurons do not send processes that synapse onto muscle; instead muscles send cellular projections to motor neurons to receive synapses. Chemical synapses are identified in electron micrographs by presynaptic darkening and synaptic vesicles; postsynaptic specializations are not obvious (Figure 4D). C. elegans uses many of the most common neurotransmitters, including acetylcholine, glutamate, \u03b3-amino butyric acid (GABA), dopamine, and serotonin and has several receptors for their detection (Hobert 2013). Gap junctions are detected in electron micrographs as parallel membranes in the closely apposed neurons. As with other invertebrates, gap junctions are formed from innexins (Starich et al. 2001). In addition to the chemical synaptic and gap junction connections, C. elegans neurons are modulated by numerous neuroendocrine signals (Li and Kim 2008). From the", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1384, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "da200f3c-0720-4147-89d8-d30ca7abdae5": {"__data__": {"id_": "da200f3c-0720-4147-89d8-d30ca7abdae5", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.12, para 1](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "13b385c5-f373-4e3e-9e06-d22cb82330d2", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.12, para 1](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "0220abc5705c71313920d99cdd60a6373491ecfddbf2be4ad6e181b1a407151a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Figure 6 C. elegans mutant phenotypes. Wild-type animals (WT) are approximately 1 mm long with a smooth exterior, and they move in a sinusoidal pattern. Rolling (Rol) animals twist their body like a corkscrew and as a result often remain in the same region moving in a circular pattern. Dumpy (Dpy) animals are shorter than wild type. Multivulvae (Muv) hermaphrodites have protrusions along the ventral side (white arrowheads) where vulvae form but are not able to attach to the uterus. Strain sources: D. Eisenmann and A. Golden.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 530, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "baa8fe7f-6cb9-43f7-9046-a9455e17b45c": {"__data__": {"id_": "baa8fe7f-6cb9-43f7-9046-a9455e17b45c", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.12, para 2](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ced02bca-dc96-47f6-9ff5-2bc081538a4b", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.12, para 2](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "84ee3380227b10649f333f9ef6c3826f7de1cefa22a0692daacd40c4dfa9a095", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "gradient of development (Hubbard and Greenstein 2005; Kimble and Crittenden 2005; Figure 5B). Studying the germline has been a model for meiosis, gamete development, fertilization, stem cell biology, and even tumor formation (Kimble and Crittenden 2005).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 254, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "74494f9e-56f0-44a8-93fa-ac6f25505552": {"__data__": {"id_": "74494f9e-56f0-44a8-93fa-ac6f25505552", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.12, para 3](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6dab20ab-3b08-450a-9153-09c4937e4862", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.12, para 3](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "10ea8582187400f5dfbdd57992885abf6898cd6f35d7af67bcd143d7afe82899", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Secondary sexual mating structures are the vulva in hermaphrodites and the fan-shaped tail in males (Emmons 2005; Herman 2006). The vulva develops in the center of the epidermis on the ventral side of the hermaphrodite and is the conduit for sperm entry from the male and egg laying from the uterus (Sternberg 2005). Studying vulval morphogenesis has provided insights into signaling by the Notch, EGF, and Wnt pathways that coordinate the spatiotemporal development of the organ. Defects in these pathways can lead to animals with no vulva \\[the egg-laying defective (Egl) phenotype] or with many vulval-like protrusions \\[the multivulva (Muv) phenotype; Figure 6]. In many cases these animals cannot lay eggs (or mate), and their progeny develop internally, hatch within the hermaphrodite, and create the \u201cbag-of-worms\u201d phenotype whereby the larvae consume the mother (a process called endotokia matricidia). This phenotype, which also occurs when wild-type adult hermaphrodites are starved, has been used to identify numerous egg-laying defective mutants. For example, details of Ras GTPase/MAP Kinase signaling have been elucidated through the identification of mutants in enhancer/suppressor screens of vulval phenotypes (Sundaram 2013).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1242, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6616519a-b432-47da-ab90-bd953052080d": {"__data__": {"id_": "6616519a-b432-47da-ab90-bd953052080d", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.12, para 4](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4511f3f3-9a9c-4452-ad9a-bf8ddcc6ac68", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.12, para 4](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "7062648b2512f76e94782750a29a3c847e85db18ec095bdf2f4d3e3b99fc6d1a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Adult males are thinner than hermaphrodites (due to their smaller gonad and the absence of developing embryos), and their tails are flattened into a fan of cuticular material with 18 projections of neurons and associated support cells called rays (Figure 3B). As with vulval development, the development of male tail structures and their associated muscles involves the coordinated action of multiple signaling pathways (Emmons 2005). Interestingly, the same signaling pathways are used in both males and hermaphrodites in the development of reproductive tissues (e.g., Wnt signaling), yet these pathways produce very different sex-specific organs and structures (Emmons 2005).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 677, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7599f4d4-36fd-49d6-bddb-b46f493ea870": {"__data__": {"id_": "7599f4d4-36fd-49d6-bddb-b46f493ea870", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.12, para 5](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b73b09a2-1213-481a-b922-a1ffa0455f5a", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.12, para 5](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "c5fd3df8a07572f025a122bbc2365701d3c6267486e42fc1ec50095cf9da9dec", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The outward morphology of males and hermaphrodites is determined by a regulatory cascade that controls the transcription factor TRA-1 (Zarkower 2006). The activity of TRA-1 depends on the X-to-autosome (or X:A) ratio. In males, TRA-1 is inactive and leads to male fate and the production of sperm. In hermaphrodites, TRA-1 is active and leads to a female somatic fate and the formation of female gametes. C. elegans also has a dosage compensation system that downregulates expression of genes on the X-chromosome in hermaphrodites to equalize X-linked expression between the sexes. A sex-specific dosage compensation complex, analogous to the chromatin condensin complex used in mitosis and meiosis, decorates the X chromosomes in hermaphrodites and downregulates X-linked genes by 50% to equal the gene expression from the single X chromosome in males (Meyer 2005).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 866, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "eeeb5c52-e138-41c8-a0a8-9ad4da1ca92b": {"__data__": {"id_": "eeeb5c52-e138-41c8-a0a8-9ad4da1ca92b", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.12, para 6](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b32cb178-7da1-4cc2-9807-bb4a79455dab", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.12, para 6](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "42aeb3a3c35f4c96a6087c80446ede7cd267471d187f618c3cac4f4eceb0661e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "perspective of cellular and molecular detail, most of the problems of neurobiology can be studied in the worm.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 110, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4117fdb6-55e7-4307-9e44-7bb56e7091c9": {"__data__": {"id_": "4117fdb6-55e7-4307-9e44-7bb56e7091c9", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.12, para 7](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cb3045ec-000b-4b4d-a2b1-e59e7f36db46", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.12, para 7](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "b88285c92ce2177f197ba90426bd62c7751f97b818f1473aa8c320cb3a361247", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In C. elegans, some individual neurons perform functions that would be performed by multiple neurons in vertebrates. For example, individual olfactory neurons express multiple G protein-coupled odorant receptors (Troemel et al. 1995; Wes and Bargmann 2001), rather than a single receptor as in vertebrates; each of the two mirror image bilateral ASE chemosensory cells respond to several different ions (Hobert 2010); and the connectivity of the touch receptor neurons suggests that their stimulation initiates several different activities (Chalfie et al. 1985). Thus, functions of multiple vertebrate sensory neurons are compressed into a single neuron in C. elegans. This multifunctionality (or \u201cpolymodality\u201d) may be an evolutionary consequence of the small number of neurons in the C. elegans nervous system. Alternatively, multifunctionality may reflect a general feature of nervous systems that was revealed by the ability to do detailed single-cell analyses with this animal.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 982, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "dd0c36cc-1151-4ab9-934d-30b4101ed73b": {"__data__": {"id_": "dd0c36cc-1151-4ab9-934d-30b4101ed73b", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.12, para 8](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3542cbee-9917-460c-8e88-6f4e1fa57988", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.12, para 8](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "839cff6d7d380229c35c7371f7323fb476801c036c9e27dbb9e811f6a7f55a6f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Reproductive tissue\u2014sex-specific anatomy", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 43, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "465b00c6-04eb-40b9-aeec-e34769545df8": {"__data__": {"id_": "465b00c6-04eb-40b9-aeec-e34769545df8", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.12, para 9](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b43a0470-a5cf-48e5-98ba-f4fac4ed6b55", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.12, para 9](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "965cbe42a366ecee8f8db11eb525c5bfe0e52d639894ae6850b4f7b5c45bcfe2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The C. elegans sexes display several obvious anatomical differences in the somatic gonad, secondary sexual structures, and body size (Figure 2, Figure 3, A and B). The somatic gonad is located in the center of the body alongside the intestine. In hermaphrodites the gonad consists of two mirror-image U-shaped tubes; in males the gonad consists of a single U-shaped lobe (Figure 3). Both gonads house the germline where the oocytes and sperm develop (Hubbard and Greenstein 2005). The somatic gonad and the germline develop together during larval stages until animals reach maturity at the young adult stage. A powerful advantage for studies of the C. elegans germline is that one can observe all stages of meiosis at once as the germline is a visible", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 751, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8ce0f30d-4add-4bc7-bfbc-9a685eb174e5": {"__data__": {"id_": "8ce0f30d-4add-4bc7-bfbc-9a685eb174e5", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.13, para 0](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d6340515-6f48-4382-a8f5-84162d4deb42", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.13, para 0](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "bad316c442d911cac0b88c72f14c365fc7ea89b96f89bc2efee24e8336ee1b1b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# The C. elegans Genome", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 23, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "058d06d8-266f-454f-b572-650945d332d0": {"__data__": {"id_": "058d06d8-266f-454f-b572-650945d332d0", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.13, para 1](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "411637a3-502c-4954-8ba6-2fe302fd108e", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.13, para 1](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "1406ab92e2d092d6bd8f587e1dc70295286262e752915e64a646b20633c26d0a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "C. elegans was the first multicellular eukaryotic organism to have its genome sequenced (C. elegans Sequencing Consortium 1998). As sequence information from additional Caenorhabditis species as well as more distantly-related nematodes has become available in the past decade, the information from C. elegans has provided the basis for rich comparative genomics studies (Coghlan 2005). The entire C. elegans genome is 100 Mb (C. elegans Sequencing Consortium 1998) and has 20,444 protein-coding genes (WormBase release WS245, October 2014). Both C. elegans sexes contain five autosomal chromosomes named linkage group (LG) I, II, III, IV, and V and the X chromosome. Individual genes of C. elegans are arranged in conventional eukaryotic fashion with 5\u2032 untranslated regions, open reading frames (ORFs) containing exons and introns, and 3\u2032 untranslated regions. Compared to vertebrate genes, C. elegans genes are relatively small with the average gene size of 3 kb due primarily to the presence of very small introns (Spieth and Lawson 2006; C. elegans genes also have many normal-sized introns). The chromosomes do not contain traditional centromeres; during mitosis the microtubule spindle attaches to more than one position along the chromosome (these attachments are said to be holocentric or polycentric). In fact, a specific sequence does not seem to be required for attachment since extrachromosomal DNA-containing transgenes can be inherited throughout many cell divisions.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1481, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "91038cb8-25f6-40d0-9dd7-4a3029eab2b8": {"__data__": {"id_": "91038cb8-25f6-40d0-9dd7-4a3029eab2b8", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.13, para 2](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e2d3bf97-8c91-4b44-91a1-9083681de3c7", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.13, para 2](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "000a9d47c55b4c57721efbf593b2eb543f2545d544f7d30eae731c4dba4326c3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The C. elegans genome has two unusual aspects: most protein-coding mRNAs are trans-spliced and some genes are organized in operons (Blumenthal 2005). Trans-splicing is the addition of one of two 22-nucleotide leader sequences (SL1 and SL2) at the 5\u2032 end of mRNA. The leader sequence is believed to aid in translational initiation and, because SL1/2 sequences are known, can be used experimentally to identify the sequence at the 5\u2032 end of mRNAs. Some C. elegans mRNAs are formed from multigenic transcripts with the first mRNA spliced to SL1 and subsequent mRNAs to SL2. The genes that code for these transcripts are closely spaced together in tandem and are transcribed under the control of a single promoter. These transcripts are similar to those produced by bacterial operons and code for gene products that are coexpressed (Blumenthal 2005). They differ, however, in that the processed transcripts in C. elegans generate multiple mRNAs. Past experiments have indicated that DNA is not methylated in C. elegans, but recent, higher resolution studies have suggested that some methylation does occur (Hu et al. 2015). Aspects of gene regulation such as transcription, translation, chromatin remodeling, and post-transcriptional modifications (ubiquitination, phosphorylation, histone methylation, and glycosylation) have all been studied using the genetic tools of C. elegans.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1378, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c5b78331-13bf-4fb0-9e13-034bd3c4a377": {"__data__": {"id_": "c5b78331-13bf-4fb0-9e13-034bd3c4a377", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.13, para 3](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "01e99813-fbb3-44cf-b8d1-9ab08a474055", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.13, para 3](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "6b827d954dac9ab006cea49faff557fe2175dfdddb44732a1606d4302e2d30cc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "considered \u201ccosmopolitan\u201d since they are found in many habitats (Kiontke and Sudhaus 2006). Although often mischaracterized as a soil nematode, larval and adult C. elegans have been routinely recovered from organic-rich garden soils, compost, and rotting fruit and plant stems, and only rarely from \u201cwild\u201d soil (Blaxter and Denver 2012; F\u00e9lix and Duveau 2012). Compost-like locations are likely to be attractive to the animals because they are abundant in the bacterial food the animals need. Outside of rotting fruits and stems, C. elegans are usually found as dauer larvae, the dispersal form of the animal. Dauer larvae are unusual in that they engage in \u201cnictating\u201d behavior, wherein they stand on their tails and wave their heads in the air (Lee et al. 2011). This activity is thought to aid in attachment of the dauer larva to other invertebrate couriers, such as isopods, so the nematode can be dispersed from a depleted food source to a new food source (Croll and Matthews 1977). Recent work on nematode ecology has included studies on wild population structures and competition between Caenorhabditis species (F\u00e9lix and Duveau 2012) and the effect of the richness of the bacterial biomass on nematode growth (Darby and Herman 2014). In addition, Rechavi et al. (2014) recently demonstrated that starvation in C. elegans leads to an upregulation of small RNAs that target nutrition genes and are inherited by multiple generations (\u201ctransgenerational inheritance\u201d) providing a mechanism for memory of past environmental conditions.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1538, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d3b2fb81-40e3-4fbb-b3fa-ee5cab886935": {"__data__": {"id_": "d3b2fb81-40e3-4fbb-b3fa-ee5cab886935", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.13, para 4](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "09ae3606-2b0d-4c08-b333-ca12d780c12f", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.13, para 4](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "4be697f669073887640997f1ed771808d583c79d4888bf49b9a2f52b61ca4b65", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Caenorhabditis and other nematodes belong to the phylum Nematoda, which is part of a larger group of the clade Ecdysozoa (Figure 7A; Bourlat et al. 2008). This clade contains organisms that shed a cuticle by molting (or ecdysis) (Bourlat et al. 2008). Therefore, C. elegans are more related to Drosophila and other insects than to mollusks, earthworms, or humans. The Caenorhabditis genus is included in the order Rhabditida, itself part of the larger subclass Chromadoria (De Ley 2006). While all known Caenorhabditis species are free living, the Rhabditidae include animal and plant parasites, as well as free-living species that exist in a variety of terrestrial and aquatic ecosystems (Kiontke and Fitch 2005). As the ecology of Caenorhabditis is increasingly better understood, more species have been identified (Figure 7B; F\u00e9lix et al. 2014). C. elegans has served as a rich starting place for comparative evolutionary studies among species. For example, developmental biologists use related nematode species to explore the changes in regulatory pathways and organogenesis that occur during evolution (Sommer 2005) and the frequent independent evolution of hermaphroditism (Figure 7B; Baldi et al. 2009).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1210, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "49255d4b-b645-48e5-82de-859f18c1baa0": {"__data__": {"id_": "49255d4b-b645-48e5-82de-859f18c1baa0", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.13, para 5](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9229e751-a113-4543-a5d4-8460a794b734", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.13, para 5](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "7a352924561ceca325916d92a27184bc121f057ab33f023ef225debe2cdc0009", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The evolutionary relationship between C. elegans and parasitic nematode species has prompted research questions with direct human health relevance. Nematode parasites of humans cause major health problems, especially in less-developed nations. These parasites include hookworm and other soil-transmitted helminths that cause malnutrition and obstructive bowel disease, filarial nematodes such as Onchocerca volvulus, which causes river blindness, and Brugia malayi, which causes lymphatic filariasis (elephantiasis;", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 515, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5a08a8a8-e3a9-44f9-8a1b-2fe2d693c8d3": {"__data__": {"id_": "5a08a8a8-e3a9-44f9-8a1b-2fe2d693c8d3", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.13, para 6](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "91fd96f0-a9fe-43b7-afa2-0a2ad32fb59d", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.13, para 6](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "fc0e419378881b22c9e70dc71cf67916ba9b8cb0bb4457679e82374e0fd30ac9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Caenorhabditis Ecology and Evolution", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 39, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b2515808-4b4a-4ac3-954b-e16d4af9884f": {"__data__": {"id_": "b2515808-4b4a-4ac3-954b-e16d4af9884f", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.13, para 7](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b26f331c-3f36-46f4-9570-de42b0f5767c", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.13, para 7](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "b0f6d327c7c19dcef69bbccdf61c163237e804942b1a2c31721461791fdda45d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In the wild, C. elegans is primarily restricted to temperate regions. In contrast, related species such as C. briggsae are", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 122, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8690058b-d97d-4de4-84cc-dd2b2459b9fa": {"__data__": {"id_": "8690058b-d97d-4de4-84cc-dd2b2459b9fa", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.14, para 1](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d69a9da9-0b24-418a-b47c-bbd0f5765090", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.14, para 1](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "f16be4906f5cb84850442022a470b723eaa859277c51b831f0e7a36befdd15cb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Figure 7 Caenorhabditis species in the animal kingdom. (A) Phylogenetic tree placing Caenorhabditis species (boxed in red) among metazoans based on sequence data from two ribosomal subunits, eight protein coding genes, and mitochondrial genomes. Image was modified from Bourlat et al. (2008). (B) Phylogenetic tree placing C. elegans (boxed in red) among named Caenorhabditis species grown in the laboratory. Species in red have hermaphrodites and males; species in blue have females and males. An \u2018o\u2019 denotes branches with low support. Image modified from F\u00e9lix et al. (2014).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 577, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e1a499c2-4d26-4441-9fb4-e97fa90e9992": {"__data__": {"id_": "e1a499c2-4d26-4441-9fb4-e97fa90e9992", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.14, para 2](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b757292e-aba9-4dcb-ad4d-6cf52b066305", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.14, para 2](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "25d87013de2f2d03a133239b395c324ee068ed46be1e46461d020812e80dd880", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Blaxter 1998). Plant parasitic nematodes cause significant crop damage (billions of dollars each year; Kandoth and Mitchum 2013) and animal parasites devastate domesticated animals (including heartworm in dogs and cats; McCall et al. 2008). *C. elegans* has played a critical role in elucidating the mode of action of anthelmintic drugs (Holden-Dye and Walker 2014). *C. elegans* may also prove useful in identifying new strategies to reduce or alleviate the action of parasitic nematodes, particularly since the emergence of resistance to current drugs (Holden-Dye and Walker 2014).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 583, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d7d6b532-a3ae-4ede-b21f-19dafcc4e5d2": {"__data__": {"id_": "d7d6b532-a3ae-4ede-b21f-19dafcc4e5d2", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.14, para 3](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "73f4bf70-4b8c-4fcb-b895-0fbb398bf973", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.14, para 3](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "99906e48e9e1395c3308691ebbac70192bc23f2a9b0e9bdf449ffe35b941443b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Brief History of *C. elegans* Research and Key Discoveries", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 62, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6d5be370-f30b-4607-ba0b-1cb07dfe1417": {"__data__": {"id_": "6d5be370-f30b-4607-ba0b-1cb07dfe1417", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.14, para 4](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b198a53c-6970-4a1d-86a1-1a405a7f2cbb", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.14, para 4](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "a8b22ebff3384a54c82eb9fd05d94592bbb2c5c003fa73816a7ab8daa6aedd3d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In Brenner\u2019s original vision, detailed elucidation of the development and anatomy of *C. elegans* would serve as the foundation for the subsequent analysis of mutants. Both of these efforts were completed primarily at the LMB. The transparency of the animal allowed John Sulston, Robert Horvitz, Judith Kimble, David Hirsh, and Einhard Schierenberg to describe every cell division starting with the single-celled zygote and ending with the adult male and hermaphrodite (Sulston and Horvitz 1977; Kimble and Hirsh 1979; Sulston et al. 1980, 1983). These efforts produced the first and only entire cell lineage of any multicellular organism. During this same time, John White, Sydney Brenner, Donna Albertson, Eileen Southgate, Sam Ward, and Nichol Thomson described the anatomy and connectivity of all 302 neurons of the adult hermaphrodite (Ward et al. 1975; Albertson and Thomson 1976; White et al. 1976, 1986). These projects set a standard for completeness in the understanding of the animal that has been a hallmark of *C. elegans* research. Such completeness was also seen in the sequencing of the *C. elegans* genome (*C. elegans* Genome Consortium 1998), the description of the wiring diagram of the adult male (Jarrell et al. 2012), and development of genome-wide feeding RNAi experiments (Fraser et al. 2000; Kamath et al. 2001). Sydney Brenner, Robert Horvitz, and John Sulston were awarded the 2002 Nobel Prize in Physiology or Medicine in part for the significance of the lineage project as a platform for discovery of genes that orchestrated developmental decisions.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1579, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e464c39f-fd58-4e13-aafb-6d73a29ebe2f": {"__data__": {"id_": "e464c39f-fd58-4e13-aafb-6d73a29ebe2f", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.14, para 5](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b74a0783-f722-4da9-95fb-11e771d0297b", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.14, para 5](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "341b24b2ec8708a33be2c5bbc524e2d2a9f8281874a250608b03a0e9d6b74247", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Since work on *C. elegans* genetics began in earnest during the 1970s, this animal has proven fruitful for making general discoveries about cell and developmental biology (Table 2). These findings have helped us understand molecular genetic mechanisms in all animals. Evolution has maintained thousands of conserved genes that play similar, or in some cases nearly identical, functions in nematodes and other animals", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 416, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e02443a0-0a0e-4222-a422-36399566cf5b": {"__data__": {"id_": "e02443a0-0a0e-4222-a422-36399566cf5b", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.15, para 1](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "46c5a167-35e6-4d69-abdf-60c05c87374c", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.15, para 1](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "4d5f41645cadba2d54e04b8190540a46519b312c0ea6ba7994a5c2362b9c3ff1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Year|Discovery|References|\n|-|-|-|\n|1974|Identification of mutations that affect animal behavior|Brenner 1974 PMID: 4366476; Dusenberry et al. 1975 PMID: 1132687; Hart 2006|\n|1975|First description of mutations that affect thermotaxis and mechanotransduction|Hedgecock and Russell 1975 PMID: 1060088; Sulston et al. 1975 PMID: 240872; Chalfie and Sulston 1981 PMID: 7227647; Mori and Ohshima 1995, PMID: 7630402|\n|1977|First cloning and sequencing of a myosin gene|Macleod et al. 1977 PMID: 909083|\n|1977|Genetic pathways for sex determination and dosage compensation described|Hodgkin and Brenner 1977 PMID: 560330; Meyer 2005 PMID: 18050416; Zarkower 2006 PMID: 18050479|\n|1981|Identification of mutations affecting touch sensitivity|Sulston et al. 1975 PMID: 240872; Chalfie and Sulston 1981 PMID: 7227647|\n|1981|First germline stem cell niche identified|Kimble and White 1981 PMID: 7202837; Kimble and Crittenden 2005 PMID: 18050413|\n|1983|Notch signaling, presenilins, ternary complex, and lateral inhibition roles in development described|Greenwald et al. 1983 PMID: 6616618; Levitan and Greenwald 1995 PMID: 7566091; Petcherski and Kimble 2000 PMID: 10830967; Greenwald and Kovall 2012 PMID: 23355521|\n|1983|First complete metazoan cell lineage|Sulston and Horvitz 1977 PMID: 838129; Kimble and Hirsh 1979 PMID: 478167; Sulston et al. 1983 PMID: 6684600|\n|1983|Discovery of apoptosis (cell death) genes|Hedgecock et al. 1983 PMID: 6857247; Ellis and Horvitz 1986 PMID: 3955651; Yuan and Horvitz 1992 PMID: 1286611; Yuan et al. 1993 PMID: 8242740; Conradt and Xue 2005 PMID: 18061982|\n|1984|Identification of heterochronic genes|Ambros and Horvitz 1984 PMID: 6494891; Slack and Ruvkun 1997 PMID: 9442909|\n|1986|First complete wiring diagram of a nervous system|White et al. 1986 PMID: 22462104; Jarrell et al. 2012 PMID: 22837521; White 2013 PMID: 23801597|\n|1987|Discovery of the first axon guidance genes|Hedgecock et al. 1987, 1990 PMID: 3308403 PMID: 2310575; Culotti 1994 PMID: 7950328|\n|1987|Identification of role of Notch signaling in embryonic blastomeres|Priess et al. 1987 PMID: 3677169; Priess 2005 PMID: 18050407|\n|1988|Discovery of \\*par\\* genes, whose products affect the asymmetric distribution of cellular components in embryos|Kemphues et al. 1988 PMID: 3345562; G\u00f6nczy and Rose 2005 PMID: 18050411|\n|1988|Identification of the first LIM and POU homeodomain transcription factors|Way and Chalfie 1988 PMID: 2898300; Finney et al. 1988 PMID: 2903797; Hobert 2013 PMID: 24081909|\n|1990|First description of a role for RAS signaling function in metazoan development|Beitel et al. 1990 PMID: 2123303; Han and Sternberg 1990 2257629; Sternberg 2005 PMID: 18050418; Sundaram 2013 PMID: 23908058|\n|1993|Demonstration of a role for insulin pathway genes in regulating lifespan|Friedman and Johnson 1988 PMID 8608934; Kenyon et al. 1993 PMID: 8247153; Kimura et al. 1997 PMID: 9252323; Collins et al. 2007 PMID: 18381800|\n|1993|Identification of genes for conserved synaptic functions|Gengyo-Ando et al. 1993 PMID: 8398155; Richmond et al. 1999 PMID: 10526333; Richmond 2007 PMID: 18050398|\n|1993|First microRNA (\\*lin-4\\*) and its mRNA target (\\*lin-14\\*) described|Lee et al. 1993 PMID: 8252621; Wightman et al. 1993 PMID: 8252622; Vella and Slack 2005 PMID: 18050425|\n|1993|Identification of nonsense-mediated decay genes|Pulak and Anderson 1993 PMID: 8104846; Hodgkin 2005 PMID: 18023120|\n|1994|Introduction of GFP as a biological marker|Chalfie et al. 1994 PMID: 8303295; Boulin et al. 2006 PMID: 18050449|\n|1994|First demonstration of specific olfactory receptor/ligand pair|Sengupta et al. 1994 PMID: 8001144; Bargmann 2006 PMID: 18050433|\n|1998|First metazoan genome sequenced|C. elegans Sequencing Consortium 1998 PMID: 9851916; Schwarz 2005 PMID: 18023117|\n|1998|Discovery of RNA interference (RNAi)|Fire et al. 1998 PMID: 9486653|\n|2000|Conservation and ubiquity of miRNAs|Pasquinelli et al. 2000 PMID: 11081512|\n|2000|Development of genome-wide RNAi screening/first full genome-wide profiling of gene function|Fraser et al. 2000 PMID: 11099033; Kamath et al. 2001 PMID: 11178279|\n|2000|Transgenerational inheritance and its mediation by piRNA|Grishok et al. 2000 PMID: 10741970; Ashe et al. 2012 PMID: 22738725|\n|2002|First cytoplasmic polyA polymerase (\\*gld-2\\*) discovered|Wang et al. 2002 PMID: 12239571; Kimble and Crittenden 2005 PMID: 18050413|\n|2005|First full-genome RNAi profiling of early embryogenesis|S\u00f6nnichsen et al. 2005 PMID: 15791247|\n|2005|First use of channelrhodopsin optogenetics in an intact animal|Nagel et al. 2005 PMID: 16360690|\n|2011|Discovery of first nematode viruses|F\u00e9lix et al. 2011 PMID: 21283608|\nPrimer 401", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4670, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e069be2c-03f6-4eb7-a64e-16978de0c9a1": {"__data__": {"id_": "e069be2c-03f6-4eb7-a64e-16978de0c9a1", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.16, para 0](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f601d8ff-c393-4595-bdcf-6faa2a482639", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.16, para 0](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "e98256ed954e5e1d58aea9e0a679f14ed144e67b5105f3305f6cab80c2708280", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "including humans (Carroll *et al.* 2004). For example, the vertebrate apoptosis regulator Bcl-2 can functionally substitute for its *C. elegans* ortholog *ced-9* (Hengartner and Horvitz 1994). Thus, discoveries with direct relevance to understanding all animals were made possible by what initially appeared to be an ambitious and esoteric undertaking to define in detail the structure and genetics of an apparently simple animal.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 430, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b5a572fa-ae99-4fec-bce7-bcebab8b0ff5": {"__data__": {"id_": "b5a572fa-ae99-4fec-bce7-bcebab8b0ff5", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.16, para 1](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "abb0f5e4-2dc0-440f-a202-4d3be2f859e6", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.16, para 1](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "6a7009c3e860147479882380114495e8756cb2db4b77a17638f035d75b76a2bb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Genetic screens in *C. elegans* have yielded a number of first discoveries of genes and pathways that play important roles in all animals. These discoveries include key genes regulating apoptosis (programmed cell death) (Hedgecock *et al.* 1983; Ellis and Horvitz 1986), the Ras and Notch signaling pathways (Priess 2005; Greenwald and Kovall 2013; Sundaram 2013), synaptic function (Gengyo-Ando *et al.* 1993; Richmond *et al.* 1999), axon pathfinding (Hedgecock *et al.* 1987, 1990), longevity (Kenyon *et al.* 1993; Kimura *et al.* 1997), and developmental timing (the heterochronic genes) (Ambros and Horvitz 1984). The study of the heterochronic genes yielded the first small regulatory RNA, the microRNA (miRNA) product of the *lin-4* gene (Lee *et al.* 1993). Robert Horvitz\u2019s 2002 Nobel Prize was awarded in part to recognize the broad significance of the genetic mechanisms of apoptosis, and Gary Ruvkun and Victor Ambros shared the 2008 Albert Lasker Award for Basic Medical Research in recognition of the general importance of miRNA.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1044, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "251e5bdf-ff90-4486-a24a-2f85ba61c300": {"__data__": {"id_": "251e5bdf-ff90-4486-a24a-2f85ba61c300", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.16, para 2](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "20f2b0dc-ee51-4572-b51a-da6aea9d958e", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.16, para 2](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "7aa2d6c09763fec0e5a8dcc78d78e664c09ce09ed37c9f7c5bee941825d680ee", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "*C. elegans* researchers also made important technical discoveries that were subsequently adapted and applied to other biological systems. For example, early gene-cloning efforts helped advance techniques for defining and assembling overlapping (contiguous) clones from animal genomes, which led to *C. elegans* being the first metazoan to have its entire genome sequenced in 1998 (*C. elegans* Genome Consortium 1998). Some of these strategies were also employed in early human genome sequencing efforts. Another discovery that led to a novel technique with broad biological impact was gene silencing by RNA interference (RNAi) (Fire *et al.* 1998). This powerful technique allows researchers working with many organisms to silence the expression of any gene and earned Andrew Fire and Craig Mello the 2006 Nobel Prize in Physiology or Medicine (Fire 2007; Mello 2007). Finally, the development of green fluorescent protein (GFP) as a biological marker (Chalfie *et al.* 1994) for which Marty Chalfie shared the 2008 Nobel Prize in Chemistry grew directly from his interest in characterizing gene expression in live (and transparent) *C. elegans*. Now GFP and other fluorescent proteins are widely-used biological tools.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1221, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a2a56a0f-3022-4a60-94a3-8c6e9471749c": {"__data__": {"id_": "a2a56a0f-3022-4a60-94a3-8c6e9471749c", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.16, para 3](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9452c41f-bf76-4b08-941b-c111155ba755", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.16, para 3](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "eeb9850298e7af37c71e5b158bc01e0023c3edafab7fe03f1fb35fa9f3063ac6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## The *C. elegans* Community", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 29, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7f5a1913-7d2a-42e4-8e07-f515170a3c66": {"__data__": {"id_": "7f5a1913-7d2a-42e4-8e07-f515170a3c66", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.16, para 4](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9e68640e-e6b0-47f4-83f1-ee86ff7727fb", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.16, para 4](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "f2068c7438e03d82017831ec244f3082ae53a51c0265e6f96b1bd0a6350c0b2f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Having mentioned all the biological reasons that *C. elegans* provides outstanding opportunities to study biological questions and all the achievements that past studies have accomplished, we would be remiss if we did not mention one other reason why the field has flourished: the community of *C. elegans* researchers. Our field has had a long tradition of openness and sharing of reagents and ideas. This openness was first encouraged by the publication of the *C. elegans* newsletter, *The Worm Breeder\u2019s Gazette*. The Gazette was started by Bob Edgar at the University of California, Santa Cruz so *C. elegans* researchers could tell each other about their research. Often work was described in the Gazette many months before it was officially published. For example, the first description of GFP as a biological marker (in the October 1993 issue of the Gazette) preceded the \u201cofficial\u201d publication by 5 months (Chalfie *et al.* 1994). The Gazette, now entirely online, is published as part of WormBook and is an excellent resource for new methods and helpful hints to aid *C. elegans* research.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1099, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "aebecac5-9d69-4d7f-8bda-b3a24fd6a4c6": {"__data__": {"id_": "aebecac5-9d69-4d7f-8bda-b3a24fd6a4c6", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.16, para 5](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "036684c6-45a5-4c8d-9e07-bd00c64812e8", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.16, para 5](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "c838626644e4395c69a1998496e3fdd7c33f4fd2962e4f711bb111ddbce00a9b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The second person to greatly support and promote a community spirit among *C. elegans* researchers was John Sulston. When John began determining the physical map of the *C. elegans* genome with Alan Coulson, one of his goals was to promote sharing. He did this by not having any independent research of his own (taking away even a hint that he might be a competitor) and by providing a service whereby any researcher could get large amounts of DNA on either side of a cloned fragment or in the region of a mapped gene. As a result, researchers did not hoard their DNA before publication and investigators benefited by having clones of entire genes. The mapping project was able to link the physical (DNA) and genetic (recombination) maps. Consequently, several collaborations were initiated because scientists shared their data before publication (e.g., Savage *et al.* 1989; Miller *et al.* 1992). As the mapping project turned to the sequencing of the *C. elegans* genome, John made sure that the openness continued; results of the sequencing project were made available daily. This same approach was used when John and Alan along with Bob Waterston and many others turned to sequencing the human genome.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1206, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "598669b2-0956-48d1-81d8-2e2cb2c8893a": {"__data__": {"id_": "598669b2-0956-48d1-81d8-2e2cb2c8893a", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.16, para 6](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "63e8146d-a517-4964-8a93-e23f3795716f", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.16, para 6](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "911ee42e810365869544669e09caeed5de59e36d6642d2c82308e71981589a9a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "A field with many thousands of researchers cannot be as closely associated as in the early days when virtually all researchers knew one another because they were Sydney Brenner\u2019s F1 and F2 progeny. Nonetheless, the *C. elegans* field continues to share resources and information. The many free online resources (Table 1), the *Caenorhabditis* Genetics Center, and the many large, community projects (e.g., ModEncode Project, National Bioresource Project for the Experimental Animal *C. elegans*, and *C. elegans* Gene Knockout Consortium) show that the sharing spirit continues. This spirit and the general enthusiasm of *C. elegans* researchers are also evident at the biennial *C. elegans* and the many alternate-year special topics and local meetings. *C. elegans* has also proven a useful system for undergraduate and even high school education. The field continues to grow and to share.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 891, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "31549ef4-8464-48b0-9580-76e3fb07d886": {"__data__": {"id_": "31549ef4-8464-48b0-9580-76e3fb07d886", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.16, para 7](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1761aa1e-4ba4-4a93-8fb4-d07686829716", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.16, para 7](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "9d783f50d10803b5a16af9fa5177ddb097f5ae91c5cf58fcca6c19549fd29569", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Looking to the future, *C. elegans* will continue to be an important source of scientific discoveries. Many of the reasons for past successes will aid future research, especially the ability to look at individual cells within the context of the entire animal. Soon genome editing should generate", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 295, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5b8c1426-2e41-4f90-9c6f-8cf3d7d6573a": {"__data__": {"id_": "5b8c1426-2e41-4f90-9c6f-8cf3d7d6573a", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.17, para 0](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "da4ade99-f7b4-4683-8703-d0864401fbf6", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.17, para 0](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "eeafb8d2ecec435df21b5a40d14022041f0ee4b9769e1a8c436afc5327a3ea0d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "loss-of-function alleles and transcriptionally and translationally tagged reporters for every gene in the genome allowing structure/function studies of all the genes and their encoded products. In addition, analysis of the ever-increasing collection of regulatory RNAs certainly will add to our understanding of the development and adaptability of *C. elegans*. Continued use of optogenetics on larger and larger sets of neurons and the analysis of the functional expression of neurotransmitters, neuropeptides, and their receptors and of gap junction proteins is likely to produce the first integrated view of the working of a complete nervous system. Investigations using *C. elegans* promise to generate insights into new areas, such as host\u2013pathogen interactions, synthetic biology, and ecology. Finally, we are confident that new and unexpected discoveries made in *C. elegans*, as they have done so often in the past, will change our views of how organisms develop, live, and age. We invite you to join us to be part of this exciting future.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1047, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "06d9af45-3f2b-4292-9af2-c9e7b42afc5d": {"__data__": {"id_": "06d9af45-3f2b-4292-9af2-c9e7b42afc5d", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.17, para 1](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9ad9c36f-d79b-4493-93d3-fe278610099f", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.17, para 1](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "8476c86b7c895a27dd6bb4208cad8b53887db89ce4473565b3012c2b0d666532", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Acknowledgments", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 18, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c7feda1e-9bc3-40b8-8e90-ae6fc73ed89a": {"__data__": {"id_": "c7feda1e-9bc3-40b8-8e90-ae6fc73ed89a", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.17, para 2](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "25d780f1-d724-4049-bc03-3c04e7303d3c", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.17, para 2](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "ca816d83beee78a141cb677dcb419b8c64b560c95292b843f7addaf1d09350ce", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We thank the following individuals for helpful discussions and manuscript improvements: Oliver Hobert, Jonathan Hodgkin, Beth De Stasio, Eric Haag, Andy Golden, and members of the WormBook Editorial Board. We also thank Christopher Crocker and David Hall for the original illustration files that were modified in Figure 3. Research in M.C.\u2019s laboratory is supported by National Institutes of Health (NIH) grant GM30997, in B.W.\u2019s laboratory by NIH grant R15GM107799, and in A.K.C.\u2019s laboratory by past grants from the National Institute of Dental and Craniofacial Research at NIH.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 580, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0b27d848-2a9c-4c0c-a9fd-ef2d0a7baf10": {"__data__": {"id_": "0b27d848-2a9c-4c0c-a9fd-ef2d0a7baf10", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.17, para 3](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "04305512-f29c-47bf-b874-fc24e6afe620", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.17, para 3](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "76707d88e206a558cf6d3c714edfe97a0a99bfa054a1014aa522d6154b2cb518", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Literature Cited", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 19, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "93a0a5ae-94e0-4c95-a7e3-6ac2c9deb016": {"__data__": {"id_": "93a0a5ae-94e0-4c95-a7e3-6ac2c9deb016", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.17, para 4](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1bd3b2af-c7a6-4f05-8006-132b4c9170f6", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.17, para 4](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "8cd0f8ccf1feeb22400ff07fef52a3b9b9f58764aa3639ada80b790adb0a2be2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* Ahringer, J., 2006 Reverse genetics (April 6, 2006), *WormBook*, ed. 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The *C. elegans* Research Community, *WormBook*, doi/10.1895/wormbook.1.10.2,", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 188, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "86e377b3-9003-4afd-a17c-fd40a3c010fe": {"__data__": {"id_": "86e377b3-9003-4afd-a17c-fd40a3c010fe", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.18, para 53](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "200bb028-d801-4f77-90a4-94bdd3a12b8a", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.18, para 53](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "4c8193b07c86a75d310ab4b9d87be28e04f654251a8916621468d1f24e0081d2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ".", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4e32420b-2016-4b09-96fa-ac4c87f38353": {"__data__": {"id_": "4e32420b-2016-4b09-96fa-ac4c87f38353", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.18, para 54](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "234195d9-aec3-4d80-8835-ff3da72cd365", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.18, para 54](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "056da52932761c226abd25fe2e1a0fb68b3d24717a5ef9822bc8b26569e8ad65", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Greenwald, I., 1985 lin-12, a nematode homeotic gene, is homologous to a set of mammalian proteins that includes epidermal growth factor. Cell 43: 583\u2013590.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 155, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "31d82b04-b4c8-4d5a-9ab8-bf41b3b3cc3e": {"__data__": {"id_": "31d82b04-b4c8-4d5a-9ab8-bf41b3b3cc3e", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.19, para 1](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a25bcf54-9ac1-4896-8113-97e38d207016", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.19, para 1](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "9c38a806fd04c5c7118231ecd2cbde67c27f67a55859986f3a92e0e27284bfd5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Greenwald, I. S., P. W. Sternberg, and H. R. Horvitz, 1983 The lin-12 locus specifies cell fates in Caenorhabditis elegans. Cell 34: 435\u2013344.\\\nGrishok, A., H. Tabara, and C. C. Mello, 2000 Genetic requirements for inheritance of RNAi in C. elegans. Science 287: 2494\u20132497.\\\nHammarlund, M., and Y. Jin, 2014 Axon regeneration in C. elegans. Curr. Opin. Neurobiol. 27: 199\u2013207.\\\nHan, M., and P. W. Sternberg, 1990 let-60, a gene that specifies cell fates during C. elegans vulval induction, encodes a ras protein. Cell 63: 921\u2013931.\\\nHart, A. C., 2006 Behavior (July 3, 2006), WormBook, ed. 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The C. elegans Research Community, WormBook, doi/10.1895/wormbook.1.84.1,", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 153, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "62531a4e-4ee8-49ff-bf56-97dabc01baac": {"__data__": {"id_": "62531a4e-4ee8-49ff-bf56-97dabc01baac", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.21, para 49](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9196f6bb-317e-4ecb-9dc3-a495632f3a73", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.21, para 49](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "4699bc5e0fbcf0ea5b2bd2e2333c6e2ba2094a01ee4d3142f4fc25bd8b26d1b5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ".", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b0d3cfbf-b57f-4a86-b8e2-3918dfe65151": {"__data__": {"id_": "b0d3cfbf-b57f-4a86-b8e2-3918dfe65151", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.21, para 50](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "416372f6-ec9e-4114-9653-a9b213d17cf6", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.21, para 50](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "a3a08b93ef717ca5337f0e6bb227fb5f1471da3e532f1e97e6e9e45f05bc97cd", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Zhang, S., D. Banerjee, and J. R. Kuhn, 2011 Isolation and culture of larval cells from C. elegans. PLoS ONE 6: e19505.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 119, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a5422392-7450-4c1e-b495-1a88a086e46a": {"__data__": {"id_": "a5422392-7450-4c1e-b495-1a88a086e46a", "embedding": null, "metadata": {"source document": "Publication: [PrimerOnCElegans, p.21, para 51](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4708537d-aa05-44fb-95a1-a295d277ca71", "node_type": "4", "metadata": {"source document": "Publication: [PrimerOnCElegans, p.21, para 51](https://academic.oup.com/genetics/article/200/2/387/5936175)"}, "hash": "d8c71d3c47fe3015765c7c1c440312fd8249b78ec9b010fdc0f18950e3163ff0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Zuryn, S., S. Le Gras, K. Jamet, and S. Jarriault, 2010 A strategy for direct mapping and identification of mutations by whole-genome sequencing. Genetics 186: 427\u2013430.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 168, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8f931373-e150-4d20-9fbf-42d4645ac2d6": {"__data__": {"id_": "8f931373-e150-4d20-9fbf-42d4645ac2d6", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.1, para 0](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ea67200e-1795-40a4-8013-2ff9b965235b", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.1, para 0](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "217fa2e14bb79a48aea0abd38e3c78961170ddf22aad1e41fbbaee191cf30dd2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Available online at www.sciencedirect.com\n**ScienceDirect**\n**Current Opinion in Systems Biology**\nELSEVIER", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 107, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "36bebc54-8c3c-4c74-b255-b68365db581a": {"__data__": {"id_": "36bebc54-8c3c-4c74-b255-b68365db581a", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.1, para 1](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f7a015c5-24fa-4556-98dc-494b52e43781", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.1, para 1](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "9b31ae7d7497b5b67f55d0c657fe44777c02a9490ae9b3e91e3fe9bf19d13177", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Whole animal modeling: piecing together nematode locomotion", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 61, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "34b285d6-a7d1-426b-bc1d-74686f52092c": {"__data__": {"id_": "34b285d6-a7d1-426b-bc1d-74686f52092c", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.1, para 3](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b245b99e-5f98-4f73-b0ad-942821490ee7", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.1, para 3](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "da76c7730fa65d3d85a265acae179219d5c11fcf0b69c3f3db9c05c631cf28f4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Abstract**\nWith a reconstructed and extensively characterized neural circuit, *Caenorhabditis elegans* is a fascinating model system for the study of neural circuits and behavior. Here, we review the recent progress in the study of locomotion in this animal from a systems perspective. We discuss how complementary approaches, from network science, through dynamical systems to biomechanics are transforming the current understanding of this system into a unified whole animal description. This transformation has been achieved through the integration of mechanistic studies and decompositional approaches: on the one hand, mapping the components of the system and their functions and on the other hand, providing qualitative and quantitative methods to probe the physical basis of locomotion, motor behavior, neural dynamics, and structure\u2013function relation in neural circuits.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 880, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a3f3e767-8ac9-45b9-adfc-9fe45aa00e3e": {"__data__": {"id_": "a3f3e767-8ac9-45b9-adfc-9fe45aa00e3e", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.1, para 7](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e89b08f8-51f8-49e9-ba1c-d5c8fb99f98a", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.1, para 7](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "030cb1ea0cd1110968795ae716905c8cb39fce02cb9763c7f564bd772e83080c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Current Opinion in Systems Biology** 2019, **13**:150\u2013160\nThis review comes from a themed issue on **Systems biology of model organisms**\nEdited by **Denis Dupuy** and **Baris Tursun**\nFor a complete overview see the Issue and the Editorial\nAvailable online 12 December 2018", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 276, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3a6347ae-9040-4f0e-8771-f9d3b0038f10": {"__data__": {"id_": "3a6347ae-9040-4f0e-8771-f9d3b0038f10", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.1, para 8](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9757b0dc-3326-4912-bcd8-7c25c43321b1", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.1, para 8](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "7092d6c9032a9171dfd2ec95c990b75f941e606ffb536b1388a478d88fabe807", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "2452-3100/\u00a9 2019 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 113, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "425ea376-3de0-46cd-b93f-46a8a7ac803d": {"__data__": {"id_": "425ea376-3de0-46cd-b93f-46a8a7ac803d", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.1, para 9](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2c2cfb02-6b0d-4857-a9c4-a6f4f5a6a60c", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.1, para 9](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "ad937316f1ffdc9bc750a7a44e4cd65478a39444aeb9c816aa739cb19f76d896", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ").", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1a70955c-1396-4293-ba0d-8d207c2bba07": {"__data__": {"id_": "1a70955c-1396-4293-ba0d-8d207c2bba07", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.1, para 10](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "120b9e1b-ceab-4f3a-b8a7-ab24fa061e5f", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.1, para 10](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "b53c7af0cd61ed94730c039172668c7185354a89dd027ffd1f93f4bb0be0da01", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Introduction", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 15, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3ad13523-bd56-4135-951d-331454cc7536": {"__data__": {"id_": "3ad13523-bd56-4135-951d-331454cc7536", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.1, para 11](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a81ee017-24eb-49fb-85a9-6988e7cd8141", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.1, para 11](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "dfebdcae8c3235bf0f11f0d567e90e06413ed8b4c5aad5bdd946ac723f41dd3f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Deciphering the neural control of behavior is a systems challenge that requires integration of structure, function, and dynamics across scales, from the gene to the behaving animal. Here, we review recent progress in our understanding of a subset of behaviors in the model organism *Caenorhabditis elegans*, with a focus on progress and open challenges for systems modeling.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 374, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "12b80a02-c327-4fa9-a6d7-e7217a767041": {"__data__": {"id_": "12b80a02-c327-4fa9-a6d7-e7217a767041", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.1, para 12](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "59dd52d2-0fcb-4af6-a7f0-5a184374a173", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.1, para 12](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "a1a6a4f2b7ffd6dc6bba9cfbafd0608cd5701ae7283914740ca9c17ee5258c3a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In comparison to humans, the anatomical structure of nematodes is remarkably simple. *C. elegans* has a fully mapped and invariant cell lineage; the adult hermaphrodite has 959 somatic cells including 95 body wall muscles and precisely 302 neurons (with a fully mapped connectome \\[1\u20134]). The slender, 1 mm long animal is lined with muscles that are controlled by a relatively distributed nervous system.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 404, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "742b0ac3-9ebc-406f-8e4c-9d24e7697caa": {"__data__": {"id_": "742b0ac3-9ebc-406f-8e4c-9d24e7697caa", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.1, para 13](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c67476eb-51f5-431a-a8fe-dea495f67284", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.1, para 13](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "fd3397a23043a1af7e9e2b542eb94252fe757917fe01ae36a7258783a406a718", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The compact and small nervous system of nematodes precludes the complex organization of the human brain, as well as many neural functions. Nematodes have no visual or auditory system or any obvious evidence of neuronal representations of complex spatial or other features, nor do they possess limbs or any means of complex communication. Yet, they are fully functioning, free-living animals that can forage for food, escape predation, and effectively navigate complex physical terrains and rich chemical environments. These are the elementary functions of nervous systems that are common to most animals. Not surprisingly, these tend to be heavily reliant on locomotion. *C. elegans* and its neural control of locomotion offer us a window to focus on the principles and mechanisms behind these essential behaviors.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 814, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9984a2b9-a5fa-4646-8d78-1f8091321a9f": {"__data__": {"id_": "9984a2b9-a5fa-4646-8d78-1f8091321a9f", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.1, para 14](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6f6fe195-e36e-46f1-9dd1-0f9fe595e1c5", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.1, para 14](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "fea3c8060c2e8c907d1fe719d40b53c03e5017a672e12f0fd9b7710d67854696", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In the lab, the movement of *C. elegans* is studied predominantly on the surface of agar gels. Here, nematodes lie on one side of their body (either left or right) and undulate in the dorsoventral plane, propagating waves from head to tail and pushing against the substrate to generate forward movement. Occasionally, animals will reverse the direction of their undulations to move backward. Backward movement is often implicated either in escape or in reorientation. To turn, animals can either gently steer by biasing head and neck undulations, with the body following suit \\[5\u20138], or turn more sharply, by deeply bending the body into stereotypical omega or delta body shapes \\[9\u201311] and emerging in a new orientation. Deep bends that mediate an escape response can generate a near 180\u00b0 reorientation \\[12], whereas other turns, typically observed during area-restricted search, foraging, and chemotaxis, generate more broadly distributed reorientations \\[10,11,13]. Studies in other physical environments demonstrate the ability of the animal to robustly adapt its waveform and kinematics to the surrounding environment \\[14\u201317].", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1133, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c4d2b0ab-cd09-4990-a60d-bdcc572b7229": {"__data__": {"id_": "c4d2b0ab-cd09-4990-a60d-bdcc572b7229", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.1, para 15](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2c3d42a3-ea8e-4053-8d1d-8a1321d77af0", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.1, para 15](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "63b6e65b6e2d974b0d5403285b14c07ef6be05961431d4b6ec8608c94bacfef1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Common topological structures across nervous systems", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 55, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d6a43d8e-baf2-4c1d-badb-89c44832f5d9": {"__data__": {"id_": "d6a43d8e-baf2-4c1d-badb-89c44832f5d9", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.1, para 16](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "264a2f41-ff57-4e6a-ba4a-92efa89ac30b", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.1, para 16](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "3caac44848037567f7141a25a827cebe0f2ea78f32fef27188ca4afca3a7bca5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The known structure of the *C. elegans* nervous system provides an excellent starting point for linking neural", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 110, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a9d1bf2b-e263-4e19-a30d-03439f295d5e": {"__data__": {"id_": "a9d1bf2b-e263-4e19-a30d-03439f295d5e", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.1, para 17](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1841209b-198d-42fa-9775-41ff0a630cc5", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.1, para 17](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "a217c1c77457b5ef53702d02e3ce4b972f70d7df0661ef11dbd8e4ec41e21744", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Current Opinion in Systems Biology** 2019, **13**:150\u2013160\nwww.sciencedirect.com", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 81, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d10697b2-dbd2-4798-b865-e0db5f4677b8": {"__data__": {"id_": "d10697b2-dbd2-4798-b865-e0db5f4677b8", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.2, para 1](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3d9bb5f6-975f-4c41-8279-b05e4031d40a", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.2, para 1](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "7d284420ded6a6b719c802144932f38813b2b6d1dd63875c1ed2c11372b43280", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "dynamics with behavior. While the size and organization of vertebrate and nematode nervous systems are vastly different, some broad principles appear to unify them, including a hierarchical structure with high clustering and a small-world organization \\[18]. Hierarchical structure refers to a multiscale architecture with nesting of modular subnetworks, whereas high clustering corresponds to local features, often manifesting in a large proportion of connected three-node subcircuits \\[19\u201322]. Studies also find similar topological features connecting low-level (microcircuit) clusters or network motifs with the modular high-level (brain-wide) architectures. Specifically, both small-world and rich-club organization have been identified in the wiring of the *C. elegans* nervous system \\[18,23] and high-level connectivity in the human brain \\[24].", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 852, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "95672db2-c86b-4186-92a9-0ca2679cf481": {"__data__": {"id_": "95672db2-c86b-4186-92a9-0ca2679cf481", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.2, para 2](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "60d06be9-72c7-4e5e-86d0-e5698b78a711", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.2, para 2](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "767cb21893ed491fca9345313aa22923dc30ea38d947c761873f16b458191d28", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In small-world networks, most neurons can be reached from every other neuron through a small number of synaptic connections; the short distances or path lengths between neurons are often mediated through high-degree hub nodes. Rich-club networks contain hub nodes that are themselves disproportionately interconnected, a topology that may serve to enhance the robustness and resilience of certain network functions. In both *C. elegans* and the human brain, these features of network topology suggest a great deal of coordination between specialized subcircuits. As in the human brain \\[24], so in *C. elegans*, the rich club has been linked with whole brain communication \\[25]; in *C. elegans*, however, the prevalence of locomotion interneurons in the rich club (Figure 1a) indicates a direct and strong coupling between sensory information, global brain dynamics, and motor behavior \\[25,26]. This is not surprising given the importance of locomotion for the survival of the animal.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 986, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9f5efcc9-9923-46f6-a2d4-e909f5a2eeb7": {"__data__": {"id_": "9f5efcc9-9923-46f6-a2d4-e909f5a2eeb7", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.2, para 3](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "726060f4-3a71-4f15-b810-a6b073feb336", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.2, para 3](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "3bda25b672e0ac3303aecb69fb0452d96f53505780b99009f7031f6ca9d8e8cb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The mapped connectome and ability to target, manipulate and record from identified neurons in *C. elegans* have meant that most neuron classes are identified with specific subcircuits and motor behaviors, including a number of locomotion interneurons driving forward and backward locomotion \\[25,27\u201330]. These locomotion interneurons act as on/off switches to gate distinct forward and backward locomotion circuits in the ventral nerve cord (VNC). Importantly, all but one of the set of rich-club neurons identified corresponds to locomotion interneurons, pointing to the essential role of this circuit for the survival of the animal.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 634, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "310de2ee-cbe8-4adf-8a0f-5701fb414579": {"__data__": {"id_": "310de2ee-cbe8-4adf-8a0f-5701fb414579", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.2, para 4](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d96531b2-6474-4eb6-af5a-996209ae6daf", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.2, para 4](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "39cdb9cb90be26f00449082bc17837cbebcdd5969cfa149baa5b9dc874b40663", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## From structure to function", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 29, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "63b13a10-f139-480c-b5f3-da56793ce6a7": {"__data__": {"id_": "63b13a10-f139-480c-b5f3-da56793ce6a7", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.2, para 5](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bc810a9f-2676-46b5-9390-26de84247e7c", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.2, para 5](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "1447d40c1130aaeb5c1ad4de87db266f13bbcc918b0f2ea66301fcdecfd7e4ec", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Network theory offers tools for inferring function and dynamics from topology. However, to learn about *C. elegans* dynamics from this advancing mathematical field, we must tread carefully. For example, it is tempting to interpret the feed-forward network motif, so prevalent in the *C. elegans* sensory system, as a logical AND gate \\[19], but there is as yet no experimental demonstration of corresponding dynamics. Similarly, the short path lengths, coupled with the small number of hub nodes, are often interpreted as mediating rapid communication and synchronization among nodes or brain areas, but a recent simulation study shows that the governing time scales of dynamics on the *C. elegans* connectome are not a straight forward consequence of either path length or in-degree (i.e. the number of presynaptic connections) \\[31]. On the one hand, that study suggests that the *C. elegans* circuit is in some sense optimized for fast, coordinated control but on the other hand that we still lack the network theoretic tools to pin down the corresponding structure\u2013function relation. An alternative approach is to consider the connectome as a test bed for evaluating network theoretic tools and the validity of their assumptions.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1233, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b92cd7b8-eb45-43b8-b5eb-16c1c9d0adf9": {"__data__": {"id_": "b92cd7b8-eb45-43b8-b5eb-16c1c9d0adf9", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.2, para 6](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e032ffe0-d2d2-4dfe-acb7-179eb246662d", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.2, para 6](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "34c8ed5c0009c204240f71d6327f8eabfd828574a7a547a4ccd0044ca7886084", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Controllability of the *C. elegans* nervous system is one example of this alternative approach. Yan et al. \\[26,32] use control theory to ask which muscles can be independently controlled and which neural nodes and pathways control specific muscles or specific motor behaviors, focusing on the locomotory response of the animal to gentle touch. Within the framework of the model assumptions and subject to the limitations of the available connectome \\[2,3], the authors find that 89 of the 95 body wall muscles are independently controllable. Furthermore, elimination of specific classes of neurons only rarely leads to a reduction in the number of independently controllable muscles, indicating that this level of controllability is robust: In this model, only 12 classes of neurons appeared to reduce controllability, and all but one of these loci of controllability are identified with the locomotor circuit \\[23,32].", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 920, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "da140b89-b786-468e-98b0-ba15e4467e7a": {"__data__": {"id_": "da140b89-b786-468e-98b0-ba15e4467e7a", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.2, para 7](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "12b2c1c6-4ca4-4be2-861d-28d38531044a", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.2, para 7](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "d56ec9907711280f9f8b9c73ea8a987f4c748c7a5934ca63caf577ceba6f55df", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Naively, the ability to independently control 89 body wall muscles suggests the potential for rich neuronal dynamics and a vast space of possible patterns of muscle activation. In fact, although the worm exhibits a rich repertoire of motor behaviors, these behaviors appear highly coordinated and involve smooth propagation of muscle activation along its slender body. Given the strong assumptions of the model \u2014 linear dynamics subject to a single governing time scale \u2014 the level of controllability is best interpreted as an upper bound. The apparent discrepancy with observed low-dimensional behavior points to the importance of additional factors in determining controllability and calling for further advances in network control theory to cope with these more general classes of dynamics \\[33].", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 799, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f1c471b2-ba53-4173-a8f2-d5e4dd9208e5": {"__data__": {"id_": "f1c471b2-ba53-4173-a8f2-d5e4dd9208e5", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.2, para 8](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ac1b4e0b-4603-4d41-b233-ccb3a758996a", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.2, para 8](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "76f7ebb19058e7433b5fa0e8e0aadc7d2b90762d2cf8d877b556e0156754a2e2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "One regime in which a linearity assumption may be instructive is in the immediate neighborhood of a bifurcation. Large-scale anatomically grounded computational models of the human brain best capture empirical data of spontaneous resting activity when the system operates at the critical point of an instability \\[34]. In such models, intrinsic fluctuations", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 357, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d4fbea3e-6d55-4224-99b9-e715b081b4fe": {"__data__": {"id_": "d4fbea3e-6d55-4224-99b9-e715b081b4fe", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.2, para 9](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c43c2413-f949-4e56-8579-781f9d0a46b6", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.2, para 9](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "8548c2195f94b1e8401c21b942fed508b3f0e11b8494b5f5d9cee0af92ed2258", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "www.sciencedirect.com Current Opinion in Systems Biology 2019, 13:150\u2013160", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 73, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "dbbd1c6d-2aba-4a05-a727-9decf2e7283e": {"__data__": {"id_": "dbbd1c6d-2aba-4a05-a727-9decf2e7283e", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.3, para 2](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "44120d7c-06e8-43e7-8710-ebe8e5e5caea", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.3, para 2](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "96349f07bf10acd11ccd7fb47ab7025b56d7c9edb39d7d32880c659abc42c2b4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**a**\n\\[The image shows a network diagram of the C. elegans rich club neurons. Nine classes of neurons are represented as colored circles: AIB (green), RIB (green), RIA (green), DVA (green), PVC (blue), AVB (blue), AVA (red), AVD (red), and AVE (red). A \"Sensory Input\" arrow points to RIB. Arrows labeled \"Forward Locomotion\" originate from PVC and AVB. Arrows labeled \"Backward Locomotion\" originate from AVE, AVD, and AVA. The neurons are interconnected by black lines (chemical synapses) and red lines (electrical synapses/gap junctions). Self-loops indicate intraclass synapses.]", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 584, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "da71c7d4-5e35-4b37-bb4f-a45e6cea6208": {"__data__": {"id_": "da71c7d4-5e35-4b37-bb4f-a45e6cea6208", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.3, para 3](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "432d4009-4c2b-45b9-b058-14753194d9f3", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.3, para 3](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "e1e3eb921cfbdf68ed91e8578cfbeb186e8cd861de5f35ef307fdad0e3c73d1f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**b**\n\\[The image shows a simplified locomotion motor circuit of the C. elegans VNC as repeating neuromuscular units. It features a series of neurons (DB, DD, DA, VB, VD, VA) arranged between dorsal and ventral muscle rows (M). Arrows indicate connections: green arrows for excitatory synapses, red lines with circles for inhibitory synapses, and dashed blue lines for stretch receptors. The diagram is oriented from \"Head\" to \"Tail\".]", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 435, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "786f5b3c-bb54-4d26-8a8f-9ed251071e72": {"__data__": {"id_": "786f5b3c-bb54-4d26-8a8f-9ed251071e72", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.3, para 4](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d115217c-4337-48f8-b570-7008d0ceaa7f", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.3, para 4](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "350dc562d8236c33478659b4dd0f991cdf86046a190b0b35d2a1ada91aba18c8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**c**\n\\[The image shows one of six repeating neural units derived from the connectome. It is a complex wiring diagram involving motoneuron classes: AS (yellow), DA (red), DB (green), DD (blue), VD (blue), VB (green), and VA (red). The neurons are positioned between dorsal (D) and ventral (V) muscle layers. Connections are shown as lines: black and red lines for chemical synapses (width represents contact strength) and purple lines for gap junctions. The diagram is labeled \"Anterior\" on the left and \"Posterior\" on the right.]", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 530, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e618708c-8933-40a5-a656-3fabcb586dba": {"__data__": {"id_": "e618708c-8933-40a5-a656-3fabcb586dba", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.3, para 5](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "12c84c4b-19c1-402c-92b1-d572b069bc69", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.3, para 5](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "0b8f6703948c2558e1ef380a27af018c5dc68d2f527904bf9649fceb7d7c9ccb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Insights from the *C. elegans* connectome into locomotion control.** **(a)** The *C. elegans* rich club features nine classes of neurons (circles) that are prominent in sensorimotor decisions and motor commands (adapted from Towlson et al. \\[23]). AIB neurons double as first-layer interneurons, integrating over sensory inputs and as locomotion gates, synapsing onto VNC motoneurons as well as other locomotion interneurons. RIA and RIB are second-layer interneurons combining thermo- and chemo-sensory integration functions with motor control, e.g. through extensive outputs to head motoneurons. DVA head interneurons are proprioceptive and fine tune forward accelerations and reversals during locomotion; they also regulate both head and tail touch circuits. Ventral nerve interneurons that gate forward (AVB) and backward (AVA, AVD, and AVE) locomotion are innervated predominantly by anterior sensory as well as first- and second-layer interneurons. PVC interneurons integrate mechano- and chemo-sensory inputs in the tail and help gate forward locomotion. Line widths represent the number of chemical (black) and electrical (red) synapses. All self-connections denote intraclass synapses (between left and right neurons). **(b)** Simplified locomotion motor circuit of the *C. elegans* VNC, depicted as repeating neuromuscular units, has served as a basis for a number of computational models. The model circuit depicts mirror images of forward and backward locomotor circuits. Motoneurons of classes VA, VB, VD (DA, DB, DD) innervate ventral (dorsal) muscles. **(c)** One of six repeating neural units derived from the connectome (adapted from Haspel and O\u2019Donovan \\[67], updated by Gal Haspel, personal communication), including AS class motoneurons in addition to motoneuron classes in Figure 1b. Neuronal placement is determined by their muscle connectivity, and the repeating structure was obtained by selecting sufficiently strong and sufficiently repeated connections along the VNC. Gap junctions are purple. Line widths for chemical synapses represent contact strength. VNC, ventral nerve cord.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2110, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "94be7eb3-fa74-4319-a83b-649c7fc14544": {"__data__": {"id_": "94be7eb3-fa74-4319-a83b-649c7fc14544", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.3, para 6](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "956c5fc9-d791-4e08-915a-c20b05ccff8b", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.3, para 6](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "22bc0a096dc9904119770bc269438c8e7bc8c01ccf66c4177413020671f50fb3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Current Opinion in Systems Biology 2019, 13:150\u2013160 www.sciencedirect.com", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 73, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "bbff81b5-9073-4bd6-89d6-e08b7abcc9b1": {"__data__": {"id_": "bbff81b5-9073-4bd6-89d6-e08b7abcc9b1", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.4, para 1](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4f0302fe-b7c5-4536-b4f7-bec1fd6a1417", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.4, para 1](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "a49355ee6aacf503378aa8d2bc22849fd569a6a7155e7008009bf348ca3b0339", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "spontaneously trigger waves of activity \u2014 dynamical excursions to one of multiple accessible attractor states \u2014 whose form is largely dictated by the anatomical connectivity. It is therefore in this rest state that the anatomical and functional connectivities of the system can be best explored simultaneously \\[34]. Whether the same reasoning applies to *C. elegans* remains an open question and could be explored further by explicitly linearizing the dynamics near a critical point.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 484, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d523d027-274f-4fd4-ae22-8fc550dc49bf": {"__data__": {"id_": "d523d027-274f-4fd4-ae22-8fc550dc49bf", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.4, para 2](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bc326bc6-fb3a-44b3-8490-11b8358ca3dd", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.4, para 2](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "53a5c22744fa847fe2510646324fee20b1171e3f5c5f5fc2bb4a04c75c78643c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Support for the crossing of a bifurcation as the worm transitions from quiescence to arousal comes from brain-wide imaging studies of *C. elegans* \\[35]. Brain-wide imaging has now been performed both at rest and in freely moving animals \\[36\u201338], revealing complex patterns of both spontaneous and evoked activity of head neurons \\[36]. Moreover, Nichols et al. \\[35] identify global attractor states corresponding to different motor programs (and a fixed state for quiescent behavior), generalizing the concept of gating different motor behaviors through a single locomotion interneuron to brain-wide distributed networks, again supporting a picture of competition between a set of attractor states.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 701, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "dbbbbeb3-2d44-40d0-a7b4-ca59c48edce7": {"__data__": {"id_": "dbbbbeb3-2d44-40d0-a7b4-ca59c48edce7", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.4, para 3](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d2d8bbed-2cd8-4942-8a09-47b5b8f3cec7", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.4, para 3](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "81790ce2da2de2069c1d36ec3c087b66150aae7a8ad2e5cf6b9053d0a3cd53a1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "One might expect the highly recurrent topology of the circuit to give rise to sustained oscillations under external stimulation. However, simulations of a virtual connectome subject to stimulation of one node at a time \\[39] yielded stationary network states except under very strong current input to a small number of neurons. Importantly, this and follow-up simulation models also assume linear neurons with a single governing time scale \\[39,40]. Any nonlinearities in these models arise due to the synaptic and gap junctional connectivity. Therefore, if, as these models suggest, the structure of the connectome does not lend itself to spontaneous oscillations, this offers a further indication of the importance of nonlinearities in generating oscillations in *C. elegans*.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 778, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2f255114-3535-4603-bd63-880c1567857f": {"__data__": {"id_": "2f255114-3535-4603-bd63-880c1567857f", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.4, para 4](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f1297de3-8d24-4b32-b260-fa90168dba33", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.4, para 4](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "de47f0c0e0f36bbaef92b565cb7cf60a712660e71f1af5442354b2cf463165c0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Top-down insight from behavior", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 34, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0ab61d81-b364-42af-a11b-28ed0f65b47c": {"__data__": {"id_": "0ab61d81-b364-42af-a11b-28ed0f65b47c", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.4, para 5](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1d998aaa-1317-45a0-b6e1-a75bb087c9c7", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.4, para 5](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "8f32efb4f96f8b1a974892ddb7daf8663a10ae9352e1c1c72d6d0ac5fd62a30b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The aforementioned connectome-wide simulations \\[39,40] suggest that whatever the fine control of the neural circuit, the number of stable global modes supported by this circuit is low. A complementary approach is to consider the postural modes of the animal. Assessing free behavior is particularly interesting as it is not limited to stable states. Thus, it may initially seem surprising that nearly all postures of this nematode on agar can be well approximated by a very low (four to five) dimensional space \\[11,41]. Furthermore, the dynamics of these postures can be mapped to a small number of attractor states, corresponding to distinct classes of motor behaviors, such as forward movement, backward movement, and turning. Together, these results point to strong organizing principles of animal behavior: Whereas the anatomical connectome may point to up to 89 muscles that may be independently controlled, suggesting unfathomable complexity, the observed repertoire of behavior is in fact very limited, occupying specific manifolds within a low-dimensional \u2018state space\u2019.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1080, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "13685301-aac6-4b58-ae60-cb2e955c21dc": {"__data__": {"id_": "13685301-aac6-4b58-ae60-cb2e955c21dc", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.4, para 6](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5d5b1455-874d-4a81-8764-ba793e8e0a4a", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.4, para 6](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "f3cba9a386f0fb39072783339655a208e8205b1bdef494695c730175acfc82ee", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The ability to describe up to 95% of worm postures using a small number of principle components, dubbed eigenworms \\[11,41], has proved to be a powerful tool in the *C. elegans* community. Observing behavior through the lens of eigenmodes has led to the identification of a new turning behavior dubbed delta turns that occur independently of omega turns (stereotypical of the escape response), suggesting that these distinct motor programs are produced by distinct pathways. Eigenworms and other low-dimensional representations of posture have been used for genetic fingerprinting of different wild-type and mutant *C. elegans* strains \\[11,42,43]. Another application has been a powerful visualization tool for neural recordings \\[25,38], revealing a tight correspondence between global neural and behavioral states \\[25,38]. Finally, Li et al. \\[44] recently applied a machine learning approach to synthetic posture and trajectory generation; a neural network, using a brief seed of postures as input (in dimensionally reduced form), generated worm postures that were subsequently used to generate realistic trajectories in space. Such results lend further credence to the conjecture that low-dimensional neural dynamics can account for observed motor behaviors. Furthermore, the ability to synthetically phenocopy trajectories of different mutant strains provides a useful tool not only for genetic fingerprinting but potentially also for mechanistic models of neural control.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1479, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "556e35b0-1477-4bea-86b4-aef297951d23": {"__data__": {"id_": "556e35b0-1477-4bea-86b4-aef297951d23", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.4, para 7](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "72970d3b-b4ef-4c2c-86ca-58497bc0fd10", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.4, para 7](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "9c00b3d136ab7f79ae025247b3e3f7bffd4f3df72af114a3190afbb28d3e4134", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### The locomotor circuit", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 25, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8a6b87b7-744b-499f-884d-6d7d5866d922": {"__data__": {"id_": "8a6b87b7-744b-499f-884d-6d7d5866d922", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.4, para 8](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ce24f03b-c9f8-43a1-9779-bf056f5b838c", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.4, para 8](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "d19005df92709b16aa2ed25296531e6fe3e43c838d012f08f0143add3b67ed05", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The small size and relative simplicity of the *C. elegans* connectome, together with powerful genetic, molecular, and optical tools, allow for a detailed analysis of neuronal connections and functions \\[1\u20133,45,46]. The VNC runs along the body and contains eight classes of motoneurons, each with characteristic anatomy, that drive ventral and dorsal body wall muscles \\[27,47]. Early inspection of the connectivity highlighted key departures from familiar network motifs in other locomotor circuits \\[48\u201351]: The circuit in the VNC is dominated by excitatory neurons and gap junctions \\[52] rather than inhibition, raising questions about the mechanisms of pattern generation. In contrast, models of the head circuit \\[53,54] and recent experimental reports \\[55,56] indicate that the head locomotion circuit is dominated by inhibition.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 836, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "02d8406b-27c3-4189-bced-c9f7cdcbffe0": {"__data__": {"id_": "02d8406b-27c3-4189-bced-c9f7cdcbffe0", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.4, para 9](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f6b3f2f1-9dd4-44ca-9041-ff4c639a2608", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.4, para 9](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "a0e16bf8e03edd26f03ae90cab9aadc10223b3be0a83c3b2a4852f3e48e4eb81", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Systematic neuronal ablations and more recent *in vivo* calcium imaging and optogenetic experiments associated distinct classes of motoneurons with distinct motor behaviors \\[12,27,57\u201360]. Of the eight classes of motoneurons in the ventral nerve cord, forward movement (consisting of dorsoventral activation that flows from head to tail) requires VB and DB cholinergic excitatory", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 379, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "129f3f90-598e-4815-950c-c22346968699": {"__data__": {"id_": "129f3f90-598e-4815-950c-c22346968699", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.4, para 10](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "794b111a-dc92-4cc6-81e7-d9839b93781a", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.4, para 10](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "16ea2be87eb5d30caf8c1cfec67d4eea62f3ecd9dea95f0ad42deab7d26dab71", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "www.sciencedirect.com Current Opinion in Systems Biology 2019, 13:150\u2013160", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 73, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "49d80063-b6cb-4cfa-b7d7-6a284ca50572": {"__data__": {"id_": "49d80063-b6cb-4cfa-b7d7-6a284ca50572", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.5, para 1](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7886c636-11a6-4175-851d-26fecb73a86a", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.5, para 1](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "3b37ea3a8e4116f1b8054127baa82e79e2b2449ea427ea80235861d84626ae11", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "motoneurons (B-type for short, Figure 1). The backward locomotion circuit approximately mirrors the forward circuit, supporting the flow of activation from tail to head, via VA and DA (A-type) excitatory motoneurons. The only \\gamma-amino butyric acid (GABA)ergic motoneuron classes in the VNC, VD, and DD modulate undulatory locomotion but do not appear essential for crawling \\[51,57,60,61]. AS cholinergic motoneurons contribute to locomotion, but recent experiments suggest that they are not essential for rhythm generation in either forward or backward movement \\[60], and VC cholinergic motoneurons have been implicated primarily in egg laying \\[59].", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 656, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9de0e627-a952-4823-bf2b-79064d1ab4ac": {"__data__": {"id_": "9de0e627-a952-4823-bf2b-79064d1ab4ac", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.5, para 2](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "48ba5ec1-2c98-46f3-ab56-4ee9a3c8b6eb", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.5, para 2](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "9ab736963dbbf748cf46b6f058a2faf117f0b8ed8cc4e99380226980445eeb48", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "With this class assignment in hand, early descriptions of the VNC sought to view it as a set of repeating subcircuits. As the number of neurons differs from class to class, a parsimonious simplified structure was proposed, with a single neuron of each class per repeating unit \\[1,27,47] (Figure 1b). Although computational models using such simplified wiring diagrams have yielded significant insights into pattern generation and neuromechanics, \\[48,50,51,62\u201366], the reduced complexity of repeating structures risks the loss of key degrees of freedom that underpin behaviorally important forms of neural dynamics, especially if those involve previously overlooked classes of motoneurons that have a role in distributed computation. In particular, the apparent inability of such minimal representations to endogenously generate distributed locomotory patterns motivated a systematic connectomic analysis that accounted for the varying cardinality of each class \\[67,68] (Figure 1c). The resulting set of repeating units also include a previously uncharacterized motoneuron class (AS motoneurons), suggesting a role in the control of locomotion.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1146, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b0c9b459-a945-4862-af03-d0165f7b17b8": {"__data__": {"id_": "b0c9b459-a945-4862-af03-d0165f7b17b8", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.5, para 3](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "68a7f8c8-25b4-415f-a2e8-cd148b5b80b5", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.5, para 3](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "da2bba9e4070ee8a02e84b36f4136608977755f345838ce13bfb39720fbdd06d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Feed-forward and feedback models of locomotion", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 49, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0220fbe0-1950-4e63-974f-3ad6d45ca095": {"__data__": {"id_": "0220fbe0-1950-4e63-974f-3ad6d45ca095", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.5, para 4](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f31f3c55-e057-4913-84c8-3dfdf87b06fc", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.5, para 4](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "211d210fc07bea0b6d84b08ab66e5fcfa14aed0080c3bb8876f063007c784e9f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The elegant sinuous gait presents three fundamental questions \\[65,69]: How are rhythmic oscillations generated? How are they coordinated across opposite (dorsal and ventral) muscles? And, how is their propagation coordinated along the animal? Recent experiments provide the first hints that B-type neurons in the forward locomotor circuit may support distributed oscillations along the body \\[61,64], with possible coupling to a pacemaker in the head \\[61,64]; meanwhile, a number of theoretical studies have asked whether peripheral control may provide a pathway for pattern generation \\[14,40,51,63]. Whether centrally or peripherally generated, there is strong experimental evidence that the entrainment or phase coordination of these oscillations requires proprioceptive feedback \\[61,64,70].", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 797, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f542010e-235c-4f99-bad1-0d4ee1fa4860": {"__data__": {"id_": "f542010e-235c-4f99-bad1-0d4ee1fa4860", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.5, para 5](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cd70fdcb-cc34-47b4-8187-87edcb11479d", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.5, para 5](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "8106156de2e0ec19d9c31c637e8f852b8faabbb00514073bcf4a86a1bdb9db6e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "As noted previously, connectome-based disembodied models with linear neurons \\[39] have struggled to generate fictive oscillations. In contrast, Olivares et al. \\[71] considered bistable neural dynamics in a simplified connectome \\[67,68] (Figure 1c). This model exhibits distributed oscillations that are generated by three classes of motoneurons \\[71], including the newly conjectured AS motoneurons \\[67]. Importantly, however, the oscillatory motifs (obtained in this model through an evolutionary search algorithm) rely on extensive inhibition. This work reinforces the difficulty of generating endogenous oscillations without either pacemakers or sensory feedback. As a follow-up to this modeling study, direct recordings of AS activity appear to rule out their role in pattern generation, instead implicating them in the locomotion interneuron gating circuit and in modulating the kinematics of undulations \\[60].", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 920, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f5f86af4-a450-40cc-af54-a9dcdd3c7ec9": {"__data__": {"id_": "f5f86af4-a450-40cc-af54-a9dcdd3c7ec9", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.5, para 6](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d805045b-a677-43ee-8889-81b289768657", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.5, para 6](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "883759f41355e0e95c8401ef9849a0ce5681576b825c99bb0a5f1aede8cf3a82", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Pattern generation is much more easily achievable in computational models of proprioceptive control \\[49\u201351,63,72\u201374]: Local bending of one side of the body triggers stretch activation of the opposite B-type motoneurons. Either posteriorly facing \\[75] or anteriorly facing \\[64,70] proprioceptive fields can mediate robust undulations when coupled to a pacemaker in the head. But, body undulations can be generated in models even in the absence of head oscillations \\[51,63]. Bryden and Cohen \\[50] demonstrated that adding local to distal proprioception enhances the robustness of undulations, and Boyle et al. \\[51] and Denham et al. \\[63] showed that local proprioception is sufficient for crawling on agar-like substrates, but not for swimming in low viscosity liquids. Together, these models predict that the spatially extended field manifests behaviorally in more dilute media. As we see below, in these models, the frequency and wavelength of undulations are tightly coupled through the proprioceptive integration of the body posture which, in turn, depends on the time taken by the biomechanical body to bend in its physical environment.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1146, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b717136a-8611-4891-b8d5-d93120e14edc": {"__data__": {"id_": "b717136a-8611-4891-b8d5-d93120e14edc", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.5, para 7](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a2840d90-194d-4a6d-97a5-be32fc7988de", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.5, para 7](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "bb3da10465639e29e3091e1f8ea8eceed03901cb8ff176e26c41331b48c284c6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Interestingly, proprioceptively driven models have long required strong nonlinearities in B-type excitatory motoneurons \\[49\u201351,64,65,76]. Bryden and Cohen \\[50] required strongly nonlinear stretch receptor conductances in their model of B-type motoneurons, effectively yielding on-off (resting and upstate) membrane potentials. Following this work, direct electrophysiological recordings gave the first direct evidence of bistable motoneurons in *C. elegans* (the RMD neurons in the head) \\[28], inspiring Boyle et al. \\[51] to consider bistability in B-type motoneurons in their model. More recently, electrophysiological recordings provided direct evidence for bistability in both A- and B-type motoneurons \\[77]. The argument for bistability in B-type motoneurons is strengthened by intuition from engineering principles: First, the hysteresis inherent in the proposed switching mechanism provides robustness to fluctuations; second, the distinct on/off states allow for efficient alternating action of opposing muscles \\[51,65].", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1033, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "73327979-5fd5-4cf9-9be7-1e165079b69b": {"__data__": {"id_": "73327979-5fd5-4cf9-9be7-1e165079b69b", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.5, para 8](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "acdb1d4c-0b0c-4ddf-8e32-c098f06c1809", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.5, para 8](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "a6c0854e0b5128b8a6bd277505e391bee8c3a30569db9f6f8c3ed430bfc6776d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Current Opinion in Systems Biology** 2019, **13**:150\u2013160 www.sciencedirect.com", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 81, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "09bda2bc-405b-468f-8bca-2bf26bf305c7": {"__data__": {"id_": "09bda2bc-405b-468f-8bca-2bf26bf305c7", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.6, para 1](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "223c7fcc-834e-4303-92fd-4807b52f896a", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.6, para 1](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "50ae5cd3efc18d6374302c0436321a3c47ab53f22be41d3f51cedab7c08a8bb1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "A further prediction that arose from the model of Boyle et al. \\[51] is a resetting mechanism that coordinates robust antiphase activation of dorsal and ventral muscles. Whereas the conventional intuition is that D-type inhibitory motoneurons suppress muscles of the noncontracting side, this model suggests an additional rhythm generating role for D-type neurons through the inhibition of excitatory motoneurons on the ventral side (Figure 1b). This requirement arises directly from the bistability condition in B-type neurons: Without ventral inhibition, the bistable switch could lead to pairs of ventral and dorsal motoneurons being on (or off) at the same time, thus disrupting or even freezing the undulatory wave. Inhibition on one side of the body suffices to avoid such a failure, by imposing dorsoventral coordination. Importantly, the ability to discern this neuronal reset depends on the biomechanics of the locomotion: The model predicts that the contribution of neural inhibition would be masked on agar but has growing importance for rapid, swimming undulations in less viscous fluids.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1100, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "09aa97de-7202-4b38-abe6-f98d06940f7b": {"__data__": {"id_": "09aa97de-7202-4b38-abe6-f98d06940f7b", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.6, para 2](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "947621db-17d2-4c05-b039-a13f871f0a06", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.6, para 2](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "9853764cb3e9e400857007707e09020a92ad368e51c43bab9f934eab4a765d4a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "How do forward and backward locomotion patterns differ? Backward locomotion is a rarer transient behavior, lasting at most a few undulations \\[10]. A combination of studies including optogenetic, electrophysiological, and calcium imaging techniques ascribe this effect to an imbalance in the locomotion interneuron circuit \\[55,60,78,79]. Haspel and O\u2019Donovan \\[67,68] give the first hint of subtle but systematic asymmetries between the forward and backward microcircuits of the VNC. Recent experiments point to slow pacemaking A-type motoneurons in the backward circuit \\[80]. The picture that emerges assigns three roles to A-type neurons: in gating \\[64,78,79], in endogenous pattern generation \\[80], and in mediating proprioceptive feedback \\[80].", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 753, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3eed428f-089a-45b3-9e65-2399fd2de08c": {"__data__": {"id_": "3eed428f-089a-45b3-9e65-2399fd2de08c", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.6, para 3](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e2359571-b76d-46ec-ac46-2a1d05d94598", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.6, para 3](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "de46a85e449b8548eb49d64dfac4fe6331d2e5b9d481fb6604c45b2b59c06cce", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "How does the head control and modulate undulations along the body? While neuromechanical models of the body appear fully capable of realistic undulations \\[51,63], the circuit that orchestrates, modulates, and switches between different motor programs resides in the head \\[25,35,36,46]. During forward locomotion, the body clearly follows the head, and biased head oscillations that track sensory inputs can thus steer the locomotion \\[7,8,72]. Omega turns are similarly initiated in the head \\[11,12] but require the body to actively follow, for example, in one model, through a traveling wave of suppressed proprioception \\[74]. In a separate neuromechanical model, a worm lacking a VNC circuit can still follow the head on agar, although severely uncoordinated \\[73]; this model relies on proprioceptively driven oscillations generated by SMD and RMD head motoneurons. Understanding the interface between head and body circuits is complicated by the possibility of mismatched frequencies and phases between head and body oscillations \\[36,61]. Proprioceptive mechanisms are a strong candidate for coordinating the head and the body. Dorsal SMD (SMDD) neurons (implicated in steering) have now been experimentally demonstrated to be proprioceptive \\[8]. Spatially extended neural processes (posteriorly facing in SMD and anteriorly facing in the anterior-most VB motoneurons) may inform the proprioceptive range and mechanisms of such coordination \\[1,4].", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1458, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "db3d3ab5-5fa5-4adf-a85c-127adf8cb5d4": {"__data__": {"id_": "db3d3ab5-5fa5-4adf-a85c-127adf8cb5d4", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.6, para 4](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e354f3e4-e320-4847-b21e-5ed1e35b28a8", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.6, para 4](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "062fe6c60f4aefce67abbe5080c31cfb1c4626f037a95fc94dc30fa874adbb9f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Biomechanical and neuronal substrates of gait adaptation", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 59, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f4234245-d40a-49f4-96f2-aa1e584f6370": {"__data__": {"id_": "f4234245-d40a-49f4-96f2-aa1e584f6370", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.6, para 5](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "482648a2-d83a-481c-8ab2-e4142c1fdf12", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.6, para 5](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "22d4567cd755c4e99c28b5004c2dd2e8bc52b77653b1ce7306277794657f0f02", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "When *C. elegans* is placed in a low viscosity liquid, its elegant, slow and sinuous crawling gait is replaced by rapid, long wavelength, and high amplitude undulations, dubbed swimming \\[14,81]. Berri et al. \\[14] showed that swimming and crawling constitute a single biomechanical gait that is smoothly modulated as a function of the resistivity of the environment \\[15,62,65,82,83]. Boyle et al. \\[51] demonstrated that this form of gait modulation is a natural outcome of proprioceptively controlled locomotion: A single fixed-parameter and \u2018headless\u2019 model worm can produce both swimming and crawling, as well as undulations in intermediate Newtonian, linear viscoelastic and obstacle-rich environments. This form of gait modulation can be summarized by a smooth relationship between kinematic parameters: The faster the undulations, the longer the wavelength and amplitude of undulations along the body.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 909, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "65acc678-7bc7-4161-80b9-b6cbf30a3fb5": {"__data__": {"id_": "65acc678-7bc7-4161-80b9-b6cbf30a3fb5", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.6, para 6](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0116fb6a-9482-4e04-a076-ddf62df14909", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.6, para 6](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "e56016ad1e377f9e679525231c6afba692ad0cfa893d55b4881809693f377dac", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Key to understanding the interplay between the neural dynamics and biomechanics underpinning this modulation are the material properties of the body. In the case of the worm, dissecting the relative roles of essential contributing factors has relied extensively on biomechanical models, often iterating closely with experiment. Contributing factors include internal pressure and bulk elasticity \\[84], elasticity of the cuticle and muscles \\[15,85\u201389], internal viscosity of the body \\[85,87,88], and the activity-dependent regulation of muscle tone \\[90]. Some models (with various levels of abstraction) have also used the worm as a platform to characterize liquid flow and viscoelastic properties of Newtonian and complex fluids \\[14,82,91\u201393]. The aforementioned approaches to characterizing material and fluid properties require only a model of the body and surrounding environment (without neural control) to solve the equations of motion. For example, by periodically forcing the mechanical model with different waveforms and simulating the dynamics in different fluid environments, it can be shown that the modulation of waveform as a function of fluid viscoelasticity provides important kinematic advantages (minimizing power and enhancing locomotion speed) \\[89].", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1273, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "01cdccd3-e835-4345-be63-bf0c23ff1d3a": {"__data__": {"id_": "01cdccd3-e835-4345-be63-bf0c23ff1d3a", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.6, para 7](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "351c1146-e476-4f85-ad5e-b988c96e8681", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.6, para 7](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "3a5aaec18fa65e8997a32baf86dbd6839c2e3cd41306dc8fce74b79b572a3f5d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "An important test of biomechanical models lies in their capacity to advance our understanding through the integration of neural control and biomechanics in a single, whole animal model. At the software level, this", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 213, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b2139e5a-e98d-4cb8-a86b-0dd0f3635c69": {"__data__": {"id_": "b2139e5a-e98d-4cb8-a86b-0dd0f3635c69", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.6, para 8](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7f2da720-39cc-47a2-a762-c19f2c37bcb0", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.6, para 8](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "3d313041b2a1bda5f81bf9dfb804359851768b49b1d4ba5e275ae9bebeaa4c96", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "www.sciencedirect.com Current Opinion in Systems Biology 2019, 13:150\u2013160", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 73, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "98351314-7766-437f-8f9f-8ed5d032ee4b": {"__data__": {"id_": "98351314-7766-437f-8f9f-8ed5d032ee4b", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.7, para 1](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e53cae30-775d-4566-8177-5e2215372215", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.7, para 1](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "4c2e4926fa0e258efb6acb448ef4b4d402ddf23d6c98ac85a3c5b4488a698d4d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "calls for flexible interfaces between neural, muscular, and mechanical components of the model to support plug-and-play experimentation with different forms of neural control \\[63]. Furthermore, as the number of control parameters grows in a model, computational efficiency becomes of paramount importance. Several of the models mentioned previously have the capacity to support a variety of simulation experiments, including extensive parameter sweeps, leading to fundamental insights into this system. For example, Denham et al. \\[63] revisited the constraints on material properties in a model of proprioceptively driven control (akin to Ref. \\[51]) integrated into a viscoelastic shell model \\[89]. The model demonstrates how body elasticity and external drag reduce to a single universal parameter that describes the kinematics of the motion in Newtonian media and to two parameters in the case of linear viscoelastic media. Furthermore, the model predicts that only a limited range of effective body elasticity can support the full range of observed gait modulation. Importantly, the capacity of this neuromechanical model to address gait modulation benefits from the exact mathematical formulation of the model \\[89], departing from previous formulations that linearize the equations around a point in parameter space.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1325, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "75eedc8f-53c6-45db-9502-13f870fcee8e": {"__data__": {"id_": "75eedc8f-53c6-45db-9502-13f870fcee8e", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.7, para 2](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5a8e821a-b57d-443e-a2f0-59d38e4f2c47", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.7, para 2](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "eef3172144dede51aa874c5d8ae90f0ad3306c79f7f5a9bd8d4a41906a567c7d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Integrated neuromechanical models also provide a framework to test hypotheses about neural control and to identify candidate targets of internal modulation. For example, fish can independently alter activation frequency and duty cycle of centrally generated rhythms, but only some neural pathways of such modulations have been identified. *C. elegans* too can modulate its locomotion speed and some kinematic parameters. Denham et al. \\[63] asked what gait modulation would look like under proprioceptive control, focusing on the three natural targets of modulation: a change in elasticity due to the modulation of muscle tone, the activation threshold of B-type motoneurons, and the spatial range of the proprioceptive field. Targeting locomotion interneurons AVB (or AVA) or the AVB-B (or AVA-A) gap junctions in the forward (or backward) circuit directly maps to a modulation of threshold in this model. Following the aforementioned reasoning, the internal modulation of mechanical properties such as body elasticity mirrors that of environmentally (or externally) imposed gait modulation, yielding a positive frequency\u2013wavelength correlation. In contrast, internal modulation of neural parameters gives rise to the opposite relation: The higher the frequency, the lower the wavelength of undulations. This signature of internal gait modulation in the form of an inverse wavelength\u2013frequency relation is specific to proprioceptive pathways of control and is therefore unlikely to be obtained by a modulation of a central pattern generator. The result therefore lends itself to a number of direct experimental predictions that may shed light on the respective roles of central and peripheral control in *C. elegans* locomotion in the forward and backward circuits and may help identify neural pathways and targets for their modulation. For example, if A-type (backward locomotion) but not B-type (forward locomotion) neurons act as pacemakers, the modulation of their respective circuits should yield distinct kinematic signatures.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2033, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "271e8e1c-bc41-440f-8ca1-ed50e6a2e924": {"__data__": {"id_": "271e8e1c-bc41-440f-8ca1-ed50e6a2e924", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.7, para 3](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9269c943-4dc9-4eb1-a96c-ce3ef1259d01", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.7, para 3](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "a5caf0108e5003fe3ecc3301bfd1cdf3c5827cc225920cdac2b172065698d6e5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Discussion and future outlook", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 32, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d6446c5a-0ccf-46de-8234-b3a83be1d789": {"__data__": {"id_": "d6446c5a-0ccf-46de-8234-b3a83be1d789", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.7, para 4](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c9c69b41-3341-42de-8f98-5301016826e6", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.7, para 4](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "0a5604c8d9299aad044f6c88a2a52082a04e07e26bed392938c6504b386a737c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Animal locomotion is a fascinating playground for exploring the interplay among the genetic, molecular, and biophysical contributions in neurobiology; the structure, function, and dynamics of neural circuits; and the biomechanics of motor behavior. The relative simplicity of *C. elegans* has allowed for an unprecedented level of characterization and an ever-growing experimental toolkit; together, these have facilitated interdisciplinary discourse, leading to significant advances in our understanding of the locomotion system and a window into understanding the \u2018state of mind\u2019 of the worm and organization of its nervous system more generally. This review has highlighted the contributions of theory and data-driven models. A recurring thread in this review has been to highlight how different formulations of the problem can serve, not always to generate testable predictions but rather to allow for the testing and, in some cases, falsification of model assumptions.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 973, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6a679f56-6c42-4492-8baf-baad5dba2345": {"__data__": {"id_": "6a679f56-6c42-4492-8baf-baad5dba2345", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.7, para 5](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1add4ec6-4dba-4f6a-b019-9a3b1ca37fd9", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.7, para 5](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "1e83f5b69d11d8fd58f90d6c03ac7c729de6a0ac083b8c2babe3e650bc41d91a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The neurodynamics of the *C. elegans* head circuit maps onto locomotor states and is well described by competition and transitions among a small number of attractors. Transitions among motor programs are clearly evident in the switching of locomotion interneuron states that drive the motor circuits along the body. The most prevalent motor behavior \u2014 forward locomotion \u2014 is well described by a single biomechanical gait that adapts smoothly and continuously to the external physical environment. Internal regulation of muscle tone and modulation of the neural circuit allow for an impressive range and specificity of kinematic control across a range of motor programs. There is now compelling evidence for proprioceptive control of the A- and B-type excitatory motoneurons of the VNC, although specific stretch receptor proteins are yet to be identified and characterized. Recent experiments are also beginning to unravel the possible roles of distributed pattern generation along the body. The interplay between central and peripheral control is therefore an exciting topic of ongoing and future investigation. Unlike the VNC, the head circuit appears to be dominated by inhibition, and the connectome suggests a number of candidate circuits for central pattern generation. As data accumulate, models are beginning to address the sensorimotor control of oscillations in the head, the role of proprioception, and the coordination between the head and the body.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1462, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d5b42c74-baf3-463d-8118-8c20bf6b99a4": {"__data__": {"id_": "d5b42c74-baf3-463d-8118-8c20bf6b99a4", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.7, para 6](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "11575de5-954e-4bb1-9da3-abe8c030dd8b", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.7, para 6](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "d84a383072b23d2768c3d3194118a003566db6faf3cc43c2f724607c2259d9d5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Current Opinion in Systems Biology** 2019, **13**:150\u2013160 www.sciencedirect.com", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 81, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6823fc09-aca4-4b73-9322-8827adf20819": {"__data__": {"id_": "6823fc09-aca4-4b73-9322-8827adf20819", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.8, para 1](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fd5c53c5-b044-4c89-9698-4f515f8cc3bc", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.8, para 1](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "733345b1027f9509da169bf9c9a2bf8ad226c393e457f70ad08caf7ebf2f306b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "This review has focused on the connectome, neural dynamics, and behavioral aspects of locomotion, excluding the large body of research on the genetic specification of behavior \\[94], neurophysiology, and biophysical properties of neurons and muscles \\[52,78,79] and exciting advances in our understanding of extrasynaptic communication networks \\[95], with their contributions to remodeling of neurons and neural circuits.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 422, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d3cb646c-1595-47d4-ab67-4d98baba81dc": {"__data__": {"id_": "d3cb646c-1595-47d4-ab67-4d98baba81dc", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.8, para 2](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4bbe3b67-7685-4124-9b76-af1b8db09330", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.8, para 2](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "6a9e2c962582fdb2b137bb5ada3c14e0a2ded831b9c9b33cdd7c7b25d9965365", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Rapidly growing computational power, tools, and resources are facilitating a step change in the generation and analysis of big data, including static networks, behavioral, and brain-wide imaging data, or high-throughput simulation. Simulation frameworks such as Openworm \\[96\u201398] and *Si elegans* \\[99,100] are pushing the computational limits. Aimed principally at emulating the biological system, these frameworks are designed to provide unprecedented anatomical and molecular level detail of the biophysics and mechanics and are already leading to simulations of sensorimotor behavior in embodied, situated, and freely behaving model worms \\[100]. The plurality of modeling frameworks and data will allow a variety of modeling questions to be addressed, benefiting from validation across different platforms. Future progress is therefore increasingly relying on plug-and-play software environments, in which anatomically or biophysically detailed model components \u2014 and data \u2014 can be seamlessly switched on or off or interchanged with simpler, theory- or hypothesis-driven models.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1083, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "703a0b7b-6f2e-4eef-8e61-965278c93e82": {"__data__": {"id_": "703a0b7b-6f2e-4eef-8e61-965278c93e82", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.8, para 3](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "670faa05-e7da-45a0-a86d-cff7a70a6c55", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.8, para 3](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "ba00e9f68cfc845c755a149d4457d3ea142d23dde0f3c882c789e0779169c5ae", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Conflict of interest statement", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 34, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "97b5b889-c504-4535-9937-bb22dbe2c4b1": {"__data__": {"id_": "97b5b889-c504-4535-9937-bb22dbe2c4b1", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.8, para 4](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9a9dc1ed-2569-4e4a-a65d-d0fe87a472c4", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.8, para 4](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "57891b393b74b818154c7dab9725038d9f38f790ee90fc8ad9da590ba872d1d4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Nothing declared.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 17, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "24b0fd83-94c0-48c4-821b-19e8919f651c": {"__data__": {"id_": "24b0fd83-94c0-48c4-821b-19e8919f651c", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.8, para 5](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cdc34927-7111-44b2-8814-a212059f7541", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.8, para 5](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "85dc53711b5f513ae884089fa49a75e8f85c481e73dc02caa207195fc4dcd9ba", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Acknowledgements", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 20, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "44b95912-cd22-413f-9897-246a980474cd": {"__data__": {"id_": "44b95912-cd22-413f-9897-246a980474cd", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.8, para 6](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d08a704c-d50b-4160-ae46-0eac72918a7b", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.8, para 6](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "c4294e750be74ea73da5a36759cf4a80648dc74dd02cae27240b267a3cfec638", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "N.C. acknowledges funding from the EPSRC (EP/J004057/1 and EP/S01540X/1). The authors thank Thomas Ranner, Felix Salfelder, Gal Haspel, Ian Hope and Samuel Braunstein for useful discussions.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 190, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fd8463d1-9730-4c5a-b39a-4ede7a622266": {"__data__": {"id_": "fd8463d1-9730-4c5a-b39a-4ede7a622266", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.8, para 7](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "83558dee-dbd1-430e-9bd2-09712fcad30e", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.8, para 7](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "c11aef01e986ce254b9d6c569e414fae1ac6d38fbb38e2de89b2200686b2d9c7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### References", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 14, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b37e1327-cbbf-4e78-b51f-2884d9437228": {"__data__": {"id_": "b37e1327-cbbf-4e78-b51f-2884d9437228", "embedding": null, "metadata": {"source document": "Publication: [CohenDenham2019, p.8, para 8](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "45260d7e-406b-4ad0-8eb7-bc84d8e3035f", "node_type": "4", "metadata": {"source document": "Publication: [CohenDenham2019, p.8, para 8](https://www.sciencedirect.com/science/article/pii/S2452310018301082)"}, "hash": "ef9da3b7fbe8f6ad3ff71199b7936733ac3720c7718f16490d46113025abb7cc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "1. 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^2Universidade Federal do ABC, S\u00e3o Bernardo do Campo, Brazil; ^3SUNY Downstate Medical Center, Brooklyn, United States; ^4Center for Biomedical Imaging and Neuromodulation, Nathan Kline Institute for Psychiatric Research, Orangeburg, United States; ^5Erasmus University Rotterdam, Rotterdam, Netherlands; ^6Arizona State University, Tempe, United States; ^7MetaCell Ltd, Cambridge, United States; ^8Opus2 International Ltd, London, United Kingdom; ^9CNRS, Gif-Sur-Yvette, France; ^10University of Washington, Seattle, United States", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 641, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "652b3ade-d768-45ec-98e6-fa3321086da4": {"__data__": {"id_": "652b3ade-d768-45ec-98e6-fa3321086da4", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.1, para 15](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4c2f51da-b7e2-4eba-bd7e-67f26466ce64", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.1, para 15](https://elifesciences.org/articles/95135)"}, "hash": "2f376bdc576b0a615571a677fa5b94ae76cd3478a26219ed8ca952b0ec294810", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Reviewing Editor:** Eilif B Muller, University of Montreal, Canada", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 68, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9bb8cf41-6aee-49a7-9f32-416247395c23": {"__data__": {"id_": "9bb8cf41-6aee-49a7-9f32-416247395c23", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.1, para 16](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a9cc6343-5f17-45d0-9e89-c1a55f943e96", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.1, para 16](https://elifesciences.org/articles/95135)"}, "hash": "146b0f3de8b3791fb5e94dd598e10a669a382e491cf5e84c528c82431823fceb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "\u00a9 Copyright Sinha, Gleeson et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 231, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e03977c4-dab3-4316-9d54-3274d23fb739": {"__data__": {"id_": "e03977c4-dab3-4316-9d54-3274d23fb739", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.1, para 17](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2f5bcf40-0d66-4483-b590-d41e2064d439", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.1, para 17](https://elifesciences.org/articles/95135)"}, "hash": "addd27fe30b2879b52cf31d5fe79c1703e062fc9203dbb9be536f16e4dc2ccfb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### eLife Assessment", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 20, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0fc68418-f32e-48d0-8957-3b00a532a625": {"__data__": {"id_": "0fc68418-f32e-48d0-8957-3b00a532a625", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.1, para 18](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0172281a-7a89-4802-9656-a44a8c7acc9a", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.1, para 18](https://elifesciences.org/articles/95135)"}, "hash": "3d63ca4cdecd3a2a8bcdd5617e125207feaeddc602cab260507766975b341b9e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "This **important** work presents a consolidated overview of the NeuroML2 open community standard and provides **convincing** evidence for its central role within a broader software ecosystem for the development of neuronal models that are open, shareable, reproducible, and interoperable. A major strength of the work is the continued development over more than two decades to establish, maintain, and adapt this standard to meet the evolving needs of the field. This work is of broad interest to the sub-cellular, cellular, computational, and systems neuroscience communities undertaking studies involving theory, modeling, and simulation.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 640, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d14fc013-4702-4b3f-bde1-c3b075884819": {"__data__": {"id_": "d14fc013-4702-4b3f-bde1-c3b075884819", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.1, para 19](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0e5e58bb-e1ae-4135-99f8-314d71fdd4e2", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.1, para 19](https://elifesciences.org/articles/95135)"}, "hash": "773586417d798c458191acf945dfe4ec741f5fbb6ae84c6a295af5ae7b626ee9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Abstract", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 12, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d0a3a074-ed15-4691-a54f-2cba16702333": {"__data__": {"id_": "d0a3a074-ed15-4691-a54f-2cba16702333", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.1, para 20](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fee70051-1100-4ab3-8b94-9abfeb888975", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.1, para 20](https://elifesciences.org/articles/95135)"}, "hash": "81ba0824c4fdd232622189a29345528f12ab0a93ce77dc89bd1fba2de5ccaf0c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Data-driven models of neurons and circuits are important for understanding how the properties of membrane conductances, synapses, dendrites, and the anatomical connectivity between neurons generate the complex dynamical behaviors of brain circuits in health and disease. However, the inherent complexity of these biological processes makes the construction and reuse of biologically detailed models challenging. A wide range of tools have been developed to aid their construction and simulation, but differences in design and internal representation act as technical barriers to those who wish to use data-driven models in their research workflows. NeuroML, a model description language for computational neuroscience, was developed to address this fragmentation in modeling tools. Since its inception, NeuroML has evolved into a mature community standard that encompasses a wide range of model types and approaches in computational neuroscience. It has enabled the development of a large ecosystem of interoperable open-source software tools for the creation, visualization, validation, and simulation of data-driven models. Here, we describe how the NeuroML ecosystem can be incorporated into research workflows to simplify the construction, testing, and analysis of standardized models of neural systems, and supports the FAIR (Findability, Accessibility, Interoperability, and Reusability) principles, thus promoting open, transparent and reproducible science.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1464, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f677d216-ca8f-4bcf-bc5f-8eda19d3d221": {"__data__": {"id_": "f677d216-ca8f-4bcf-bc5f-8eda19d3d221", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.1, para 21](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1f87f03f-39c4-4987-b4ac-cb5080a9e9df", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.1, para 21](https://elifesciences.org/articles/95135)"}, "hash": "48e2d2caca46585f6adc3723e1457d77d4c15fb48491a41aaf85c9b37bf4a56d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135 1 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 93, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "03da519a-b995-479b-9bf2-c6de1dc74b91": {"__data__": {"id_": "03da519a-b995-479b-9bf2-c6de1dc74b91", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.2, para 1](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7e096bc9-934c-4719-86cb-c15ee88b10f8", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.2, para 1](https://elifesciences.org/articles/95135)"}, "hash": "1fb36403083337cbd4b029ec585967735f2bc7f793da418180b9c6062419dc8c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Introduction", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 14, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7db84ddb-f135-4432-bc64-d139247ba043": {"__data__": {"id_": "7db84ddb-f135-4432-bc64-d139247ba043", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.2, para 2](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "349bcb14-2333-46eb-8086-744770926f5f", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.2, para 2](https://elifesciences.org/articles/95135)"}, "hash": "38e436792c3a3188bee4be9a07b148da23bd41a565df03d2532e2272e5c78868", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Development of an in-depth, mechanistic understanding of brain function in health and disease requires different scientific approaches spanning multiple scales, from gene expression to behavior. Although \u2018wet\u2019 experimental approaches are essential for characterizing the properties of neural systems and testing hypotheses, theory and modeling are critical for exploring how these complex systems behave across a wider range of conditions, and for generating new experimentally testable, physically plausible hypotheses. Theory and modeling also provide a way to integrate a panoply of experimentally measured parameters, functional properties, and responses to perturbations into a physio-chemically coherent framework that reproduces the properties of the neural system of interest (**Einevoll et al., 2019; Yao et al., 2022; Poirazi and Papoutsi, 2020; Gurnani and Silver, 2021; Gleeson et al., 2018; Cayco-Gajic et al., 2017; Billings et al., 2014; Vervaeke et al., 2010; Kriener et al., 2022; Billeh et al., 2020; Markram et al., 2015**).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1043, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ee4ba846-cc43-4120-97a3-f285e82bef39": {"__data__": {"id_": "ee4ba846-cc43-4120-97a3-f285e82bef39", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.2, para 3](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "08d973c6-7c03-4e90-b3fc-373366e662b2", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.2, para 3](https://elifesciences.org/articles/95135)"}, "hash": "bfe072147523cb8286e11bc7241f2b753a2718049c00f07513e59003bd6ffac3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Computational models in neuroscience often focus on different levels of description. For example, a cellular physiologist may construct a complex multi-compartmental model to explain the dynamical behavior of an individual neuron in terms of its morphology, biophysical properties, and ionic conductances (**Hay et al., 2011; De Schutter and Bower, 1994; Migliore et al., 2005**). In contrast, to relate neural population activity to sensory processing and behavior, a systems neurophysiologist may build a circuit-level model consisting of thousands of much simpler integrate-and-fire neurons (**Lapicque, 1907; Potjans and Diesmann, 2014; Brunel, 2000**). Domain specific tools have been developed to aid the construction and simulation of models at varying levels of biological detail and scales. An ecosystem of diverse tools is powerful and flexible, but it also creates serious challenges for the research community (**Cannon et al., 2007**). Each tool typically has its own design, features, Application Programming Interface (API) and syntax, a custom set of utility libraries, and finally, a distinct machine-readable representation of the model\u2019s physiological components. This represents a complex landscape for users to navigate. Additionally, models developed in different simulators cannot be mixed and matched or easily compared, and the translation of a model from one tool-specific implementation to another can be non-trivial and error-prone. This fragmentation in modeling tools and approaches can act as a barrier to neuroscientists who wish to use models in their research, as well as impede how Findable, Accessible, Interoperable, and Reusable (FAIR) models are (**Wilkinson et al., 2016**).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1714, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7957e321-0eb6-471b-b725-fd6440076744": {"__data__": {"id_": "7957e321-0eb6-471b-b725-fd6440076744", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.2, para 4](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1ebd4802-0bef-49eb-9632-56214853561a", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.2, para 4](https://elifesciences.org/articles/95135)"}, "hash": "c18c25b4a4c2ceb1c83f30efff93a836c6a61a481af0be07969fda18d2be6c15", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "To counter fragmentation and promote cooperation and interoperability within and across fields, standardization is required. The International Neuroinformatics Co-ordinating Facility (INCF) (**Abrams et al., 2022**) has highlighted the need for standards to \u2018make research outputs machine-readable and computable and are necessary for making research FAIR\u2019 (**INCF, 2023**). In biology, several community standards have been developed to describe experimental data (e.g. Brain Imaging Data Structure \\[BIDS; **Gorgolewski et al., 2016**], Neurodata Without Borders \\[NWB; **Teeters et al., 2015**]) and computational models (e.g. Systems Biology Markup Language \\[SBML; **Hucka et al., 2003**], CellML \\[**Lloyd et al., 2004**], Scalable Open Network Architecture TemplAte \\[SONATA; **Dai et al., 2020**], PyNN \\[**Davison et al., 2008**] and Neural Open Markup Language \\[NeuroML; **Gleeson et al., 2010**]). These standards have enabled open and interoperable ecosystems of software applications, libraries, and databases to emerge, facilitating the sharing of research outputs, an endeavor encouraged by a growing number of funding agencies and scientific journals.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1168, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0ab33b84-6d8d-42f1-ade6-243a2d4620b3": {"__data__": {"id_": "0ab33b84-6d8d-42f1-ade6-243a2d4620b3", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.2, para 5](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "701e23ee-2418-4991-866a-484b218c9523", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.2, para 5](https://elifesciences.org/articles/95135)"}, "hash": "ffcbf4940109381492cafe7ad086d3793a0cdc91d35279aea22d8d60508cafdf", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The initial version of the NeuroML standard, version 1 (NeuroMLv1), was originally conceived as a model description format (**Goddard et al., 2001**) and implemented as a three-layered, declarative, modular, simulator-independent language (**Gleeson et al., 2010**). NeuroMLv1 could describe detailed neuronal morphologies and their biophysical properties as well as specific instantiations of networks. It enabled the archiving of models in a standardized format and addressed the issue of simulator fragmentation by acting as the common language for model exchange between established simulation environments\u2014NEURON (**Hines and Carnevale, 1997; Awile et al., 2022**), GENESIS (**Bower and Beeman, 1998**), and MOOSE (**Ray and Bhalla, 2008**). While solving a number of long-standing problems in computational neuroscience, NeuroMLv1 had several key limitations. The most restrictive of these was that the dynamical behavior of model elements was not formally described in the standard itself, making it only partially machine readable. Information on the dynamics of elements (i.e. how the state variables should evolve in time) was only provided in the form of human-readable documentation, requiring the developers of each new simulator to re-implement the behavior of these elements", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1289, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2d024f01-9f93-4545-836b-3eb059964400": {"__data__": {"id_": "2d024f01-9f93-4545-836b-3eb059964400", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.2, para 6](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "914c5c16-c616-4898-a4bf-333742c69d41", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.2, para 6](https://elifesciences.org/articles/95135)"}, "hash": "76377a7aa6568e2203fac3fa966c4d8fc8900d91613d4a07c25433a03db03ec2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135 2 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 93, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "16674d44-9b7a-427e-ae6a-279c0973ed72": {"__data__": {"id_": "16674d44-9b7a-427e-ae6a-279c0973ed72", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.3, para 1](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d2e0ac03-7ade-464b-b37f-478017a43ec0", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.3, para 1](https://elifesciences.org/articles/95135)"}, "hash": "45e544f4319153737e4a0786a8ae0e7c557b9c7d66b4cbc373765bf14113f2e3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Figure 1.** The NeuroML software ecosystem supports all stages of the model development life cycle.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 101, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "26debbb7-83c5-4023-ae19-5f1b26bdc311": {"__data__": {"id_": "26debbb7-83c5-4023-ae19-5f1b26bdc311", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.3, para 2](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fafb432a-ab88-44c3-a19a-4a47a077db9a", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.3, para 2](https://elifesciences.org/articles/95135)"}, "hash": "c1bfdb6b20c6b960b19904e5ef5595e6fe16865bae188349d2e625d4bedb6e14", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "in their native format. Additionally, the introduction of new model components required updates to the standard and all supporting simulators, making extension of the language difficult. Finally, the use of Extensible Markup Language (XML) as the primary interface language limited usability\u2014applications would generally have to add their own code to read/write XML files.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 372, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "bdd73f37-bcff-4355-8022-a4f91300fc19": {"__data__": {"id_": "bdd73f37-bcff-4355-8022-a4f91300fc19", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.3, para 3](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3216ee12-db47-4f4a-8957-24e72006df27", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.3, para 3](https://elifesciences.org/articles/95135)"}, "hash": "76164ceb58a2485379ea3f12f0b59864ec39cb62a15837341f6d52bd125b98fb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "To address these limitations, NeuroML was redesigned from the ground up in version 2 (NeuroMLv2) using the Low Entropy Modeling Specification (LEMS) language (*Cannon et al., 2014*). LEMS was designed to define a wide range of physio-chemical systems, enabling the creation of fully machine-readable, formal definitions of the structure and dynamics of any model components. Modeling elements in NeuroMLv2 (cells, ion channels, synapses) have their mathematical and structural definitions described in LEMS (e.g. the parameters required and how the state variables change with time). Thus, NeuroMLv2 retains all the features of NeuroMLv1\u2014it remains modular, declarative, and continues to support multiple simulation engines\u2014but unlike version 1, it is extensible, and all specifications are fully machine-readable. NeuroMLv2 also moved to Python as its main interface language and provides a comprehensive set of Python libraries to improve usability (*Vella et al., 2014*), with XML retained as a machine-readable serialization format (i.e. the form in which the model files are saved/shared).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1094, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "49bed470-214c-4f4c-bfba-c550d094b0be": {"__data__": {"id_": "49bed470-214c-4f4c-bfba-c550d094b0be", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.3, para 4](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1cb3f501-4f31-474d-a580-322444f07f04", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.3, para 4](https://elifesciences.org/articles/95135)"}, "hash": "f7e72a656d869be7390c5bab7481cd86b7865030e592383d13b6a3c2678a949e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Since its release in 2014, the NeuroMLv2 standard, the software ecosystem, and the community have all steadily grown. An open, community-based governance structure was put in place\u2014an elected Editorial Board, overseen by an independent Scientific Committee, maintains the standard and core software tools\u2014APIs, reference simulators, and utilities. Although these tools were initially focused on enabling the simulation of models on multiple platforms, they have been expanded to support all stages of the model life cycle (*Figure 1*). Modelers can use these tools to easily create, inspect and visualize, validate, simulate, fit and optimize, share and disseminate NeuroMLv2 models and outputs (*Billings et al., 2014; Cayco-Gajic et al., 2017; Gurnani and Silver, 2021; Kriener et al., 2022; Gleeson et al., 2019b*). To provide clear, concise, searchable information for both users and developers, the NeuroML documentation has been significantly expanded and re-deployed using the latest modern web technologies (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1016, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4cedb7bd-2427-49f6-bb53-3dc6d8a5a649": {"__data__": {"id_": "4cedb7bd-2427-49f6-bb53-3dc6d8a5a649", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.3, para 5](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ee83f100-0432-4644-9a14-a00af5bb39d9", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.3, para 5](https://elifesciences.org/articles/95135)"}, "hash": "0e17ced9f46d77634d297f7947ea6bfa4eda1da7c442b4306b090ebd79a4c3fc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "). Increased community-wide collaborations have also extended the software ecosystem well beyond the NeuroMLv2 tools developed by the NeuroML team: additional simulators such as Brian (*Stimberg et al., 2019*), NetPyNE (*Dura-Bernal et al., 2019*), Arbor (*Akar et al., 2019*) and EDEN (*Panagiotou et al., 2022*) all support NeuroMLv2. We have worked to ensure interoperability with other structured formats for model development in neuroscience such as PyNN (*Davison et al., 2008*) and SONATA (*Dai et al., 2020*). Platforms for collaboratively developing, visualizing, and sharing NeuroML models (Open Source Brain (OSB) *Gleeson et al., 2019b*) as well as a searchable database of NeuroML model components NeuroML", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 718, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fafb24e0-9f41-40a4-b37a-d51bb7f8a977": {"__data__": {"id_": "fafb24e0-9f41-40a4-b37a-d51bb7f8a977", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.3, para 6](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3779c82a-f215-456e-9e71-5e5bd74fe90c", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.3, para 6](https://elifesciences.org/articles/95135)"}, "hash": "d70e63fde9e9f01366a20fff5f70ca077d816ceec6d3493fb6d6153ea0c3c6a8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135 3 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 93, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "13c3c5f8-cd91-4f0f-bb9a-f6a8c84990f3": {"__data__": {"id_": "13c3c5f8-cd91-4f0f-bb9a-f6a8c84990f3", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.4, para 1](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "83fdd465-5bd2-477e-aa8a-a67592de2572", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.4, para 1](https://elifesciences.org/articles/95135)"}, "hash": "6c170b663791f94dd3b78cd62c52744a0733b31c612efefb45e3eb937dfee862", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Database (NeuroML-DB) (*Birgiolas et al., 2023*) have been developed. These enhancements, driven by an ever-expanding community, have helped NeuroMLv2 grow into a standard that has been officially endorsed by international organizations such as the INCF and COmputational Modeling in Biology NEtwork (COMBINE) (*Hucka et al., 2015*), and that is now sufficiently mature to be incorporated into a wide range of research workflows.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 429, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1379d1eb-891f-43ea-906a-7235de079d1d": {"__data__": {"id_": "1379d1eb-891f-43ea-906a-7235de079d1d", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.4, para 2](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6dde65d4-23f4-43f3-8c39-1e1973acba46", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.4, para 2](https://elifesciences.org/articles/95135)"}, "hash": "d398664fd80a77d90a0939095ebf00d7c423b3c915931d79ab8da4dd7a4339fd", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In this paper, we provide an overview of the current scope of version 2 of the NeuroML standard, describe the current software ecosystem and community, and outline the extensive resources to assist researchers in incorporate NeuroML into their modeling work. We demonstrate, with examples, that NeuroML supports users at all stages of the model development life cycle (*Figure 1*) and promotes FAIR principles in computational neuroscience. We highlight the various NeuroML tools and libraries, additional utilities, supported simulation engines, and the related projects that build upon NeuroML for automated model validation, advanced analysis, visualization, and sharing/re-use of models. Finally, we summarize the organizational aspects of NeuroML, its governance structure and its community.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 796, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "de4ca08c-7e8d-4442-9209-d1fc0b851e9d": {"__data__": {"id_": "de4ca08c-7e8d-4442-9209-d1fc0b851e9d", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.4, para 3](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6bfeb3fa-a0ef-4c01-be23-90437210ed1f", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.4, para 3](https://elifesciences.org/articles/95135)"}, "hash": "1f9790c2610f3986f3614cea4e1f14f74f54174a86188a47bbef0fc530e1b3db", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Results", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 9, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "facbfcc4-bdc0-414f-8f6d-1ec003a7b4a3": {"__data__": {"id_": "facbfcc4-bdc0-414f-8f6d-1ec003a7b4a3", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.4, para 4](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0fe68df3-2e9a-42be-abc6-929f00fd5a84", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.4, para 4](https://elifesciences.org/articles/95135)"}, "hash": "042a18aef1856ccfa2b59b24c27ba46e28a5d58e8b2c04b6848fece3b0c6a465", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## NeuroML provides a ready-to-use set of curated model elements", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 64, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fb44156b-e06b-4d23-8239-6e17c03dbb6c": {"__data__": {"id_": "fb44156b-e06b-4d23-8239-6e17c03dbb6c", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.4, para 5](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d82eec43-e7cd-4ecc-936b-834e45d7af07", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.4, para 5](https://elifesciences.org/articles/95135)"}, "hash": "24e5530daab4f99fdfef66a7b992f9bc1e994d967b58ee7e4980ee7d806b37a1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "A central aim of the NeuroML initiative is to enable and encourage the use of multi-scale biophysically detailed models of neurons and neuronal circuits in neuroscience research. The initiative takes a range of steps to achieve this aim.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 237, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a5997a83-81a0-43cc-a883-99dc1171c1cf": {"__data__": {"id_": "a5997a83-81a0-43cc-a883-99dc1171c1cf", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.4, para 6](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b346b5b3-b8cc-4478-bf3e-501bfc1129fb", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.4, para 6](https://elifesciences.org/articles/95135)"}, "hash": "d3328b33e113d7348a235109962cd02cd60ab1261bdfee8fbb3693b2a16d25c5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "NeuroML provides users with a curated library of model elements that form the NeuroML standard (An index of all the model elements included in version 2.3 of NeuroML, with links to further online documentation, is provided in *Tables 1 and 2; Figure 2*). The standard is maintained by the NeuroML Editorial Board that has identified a fundamental set of model types to support, to ensure that a significant proportion of commonly used neurobiological modeling entities can be described with the language. This includes (but is not limited to): active membrane conductances (using Hodgkin-Huxley style \\[*Hodgkin and Huxley, 1952*] or kinetic scheme-based ionic conductances), multiple synapse and plasticity mechanisms, detailed multi-compartmental neuron models with morphologies and biophysical properties, abstract point neuron models, and networks of such cells spatially arranged in populations, connected by targeted projections, receiving spiking and currently based inputs.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 981, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "16f57a8b-b503-401f-a0e6-5559948e1f5d": {"__data__": {"id_": "16f57a8b-b503-401f-a0e6-5559948e1f5d", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.4, para 7](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "be838c2a-c8cd-4ca1-b155-748abd6eaa60", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.4, para 7](https://elifesciences.org/articles/95135)"}, "hash": "e1f0bf87605017da16e1648e79391a767a5d4dd6b2fd68043a4f13cae1b30acc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The NeuroMLv2 standard consists of two levels that are designed to enable users to easily create their models without worrying about simulator-specific details. The first level defines a formal \u2018schema\u2019 for the standard model elements, their attributes/parameters (e.g. an integrate and fire cell model and its necessary attributes: a threshold parameter, a reset parameter, etc.), and the relationships between them (e.g. a network contains populations; a multi-compartmental cell morphology contains segments). This allows the validation of the completeness of the description of individual NeuroML model elements and models, *prior to simulation*. The second level defines the underlying dynamical behavior of the model elements (e.g. how the time-varying membrane potential of a cell model is to be calculated). Most users do not need to interact with this level (which is enabled by LEMS), which, among other features, enables the automated translation of *simulator-independent* NeuroML models into *simulator-specific* code.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1031, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "dbd6ec6b-9e68-4f63-a21b-972f0dc54f94": {"__data__": {"id_": "dbd6ec6b-9e68-4f63-a21b-972f0dc54f94", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.4, para 8](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e0c52716-c6c3-4c58-802b-c80e9ea074d2", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.4, para 8](https://elifesciences.org/articles/95135)"}, "hash": "346651bcc0f7e3815819638cd0cad5ab3dcf3131a1419a09695f0ec4236572df", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Thus, modelers can use the standard NeuroML elements to conveniently build simulator-independent models, while also being able to examine and extend the underlying implementations of models. As a simulator-independent language, NeuroML also promotes interoperability between different computational modeling tools, and as a result, the standard library is complemented by a large, well-maintained ecosystem of software tools that support all stages of the model life cycle\u2014from creation, analysis, simulation, and fitting, to sharing and reuse. Finally, as discussed in later sections, for advanced use cases where the existing NeuroML model building blocks are insufficient, NeuroML also includes a framework for creating and including new model elements.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 756, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7abcf06a-116c-4276-8a18-7f75aa5d6149": {"__data__": {"id_": "7abcf06a-116c-4276-8a18-7f75aa5d6149", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.4, para 9](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c1a32302-a137-4d98-ae89-517dee795141", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.4, para 9](https://elifesciences.org/articles/95135)"}, "hash": "ce43b7fa51d16128a73fb8c5d4bf556c1aa5a61dd307ebb357979e4a8f1a8980", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## NeuroML is a modular, structured language for defining FAIR models", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 69, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cf77a591-0dc7-40aa-b5e1-b06f540aca69": {"__data__": {"id_": "cf77a591-0dc7-40aa-b5e1-b06f540aca69", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.4, para 10](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a0819b25-5748-415c-b692-e57c8f27430f", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.4, para 10](https://elifesciences.org/articles/95135)"}, "hash": "df4492a775e2a9944fe296cbf69968040963e8cf4591fdbffd414149dd3f0622", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "NeuroMLv2 is a modular, structured, hierarchical, simulator-independent format. All NeuroML elements are formally defined, independent, and self-contained with hierarchical relationships between them. An \u2018ionic conductance\u2019 model element in NeuroML, for example, can contain zero, one, or more \u2018gates\u2019 and be added into a \u2018cell\u2019 model element along with a \u2018morphology\u2019 element, which can then", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 392, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c459a645-61bd-446f-90a1-edebac860e31": {"__data__": {"id_": "c459a645-61bd-446f-90a1-edebac860e31", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.4, para 11](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1b1de738-a6d4-4cbf-9664-ec7df1b9d09a", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.4, para 11](https://elifesciences.org/articles/95135)"}, "hash": "e0d70f94229a1667b58188067527067018fb85057ffcc3ae7299b3dd465d51c5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135 4 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 93, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "30003655-0bfb-4ce8-8042-0b8aa5bbc7dd": {"__data__": {"id_": "30003655-0bfb-4ce8-8042-0b8aa5bbc7dd", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.5, para 1](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "66d39a90-2896-41ab-ab50-48de3812d12b", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.5, para 1](https://elifesciences.org/articles/95135)"}, "hash": "db7871550f357c9f992c835275dffbf02fa6422163ea30ce7d85257b3862cebe", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Table 1.** Index of standard NeuroMLv2 ComponentTypes.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 56, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e4bfa345-dd42-4d4e-9b1d-30ac6b64c972": {"__data__": {"id_": "e4bfa345-dd42-4d4e-9b1d-30ac6b64c972", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.5, para 2](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d605a100-9d03-4cc1-a967-9a8a739ac18c", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.5, para 2](https://elifesciences.org/articles/95135)"}, "hash": "cc94cb78d6fd1e06ff7aa49b8c1fd5223849f20ef1c10de388961bc5358cbe47", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Core components|Core components|Core components|\n|-|-|-|\n|annotation|bqbiol\\_encodes|bqbiol\\_hasPart|\n|bqbiol\\_hasProperty|bqbiol\\_hasTaxon|bqbiol\\_hasVersion|\n|bqbiol\\_is|bqbiol\\_isDescribedBy|bqbiol\\_isEncodedBy|\n|bqbiol\\_isHomologTo|bqbiol\\_isPartOf|bqbiol\\_isPropertyOf|\n|bqbiol\\_isVersionOf|bqbiol\\_occursIn|bqmodel\\_is|\n|bqmodel\\_isDerivedFrom|bqmodel\\_isDescribedBy|rdf\\_Bag|\n|rdf\\_Description|rdf\\_li|rdf\\_RDF|\n|property|point3DWithDiam|notes|\n|Core dimensions|||\n|area|capacitance|charge|\n|charge\\_per\\_mole|concentration|conductance|\n|conductance\\_per\\_voltage|conductanceDensity|current|\n|currentDensity|idealGasConstantDims|length|\n|per\\_time|per\\_voltage|permeability|\n|resistance|resistivity|rho\\_factor|\n|specificCapacitance|substance|temperature|\n|time|voltage|volume|\n|Abstract cell models|||\n|adExIaFCell|fitzHughNagumoCell|hindmarshRose1984Cell|\n|iafCell|iafRefCell|iafTauCell|\n|iafTauRefCell|izhikevich2007Cell|izhikevichCell|\n|pinskyRinzelCA3Cell|||\n|ComponentTypes related to biophysically detailed cells|||\n|biophysical Properties|biophysicalProperties2CaPools|cell|\n|cell2CaPools|concentration Model|decayingPoolConcentrationModel|\n|distal|distalProperties|fixedFactorConcentrationModel|\n|fixedFactorConcentrationModelTraub|from|include|\n|inhomogeneousParameter|inhomogeneousValue|initMembPotential|\n|intracellular Properties|intracellularProperties2CaPools|member|\n|membraneProperties|membraneProperties2CaPools|morphology|\n|parent|path|pointCellCondBased|\n|pointCellCondBasedCa|proximal|proximalProperties|\n|segment|segment Group|species|\n|spikeThresh|subTree|to|\n|variable Parameter|channel Density|channelDensityGHK|\n|channelDensityGHK2|channelDensityNernst|channelDensityNernstCa2|\n|channelDensityNonUniform|channelDensityNonUniformGHK|channelDensityNonUniformNernst|\n|channelDensityVShift|channelPopulation|channelPopulationNernst|\n|ComponentTypes related to ion channels|||\n|fixedTimeCourse|forward Transition|gate|\n|gateFractional|gateHHInstantaneous|gateHHrates|\n|gateHHratesInf|gateHHratesTau|gateHHratesTauInf|", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2046, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4671828f-7b56-4a4e-99f5-99c94765be9c": {"__data__": {"id_": "4671828f-7b56-4a4e-99f5-99c94765be9c", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.5, para 4](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4c5a8286-74c3-400d-b46f-b1a1bda2ee93", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.5, para 4](https://elifesciences.org/articles/95135)"}, "hash": "da2d737d7fd818bdd265a3608b88258624f0fee75387c0b4e27c4ee791784b8d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135 5 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 93, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6cd3f708-a126-4878-9d11-e23d27cc72b2": {"__data__": {"id_": "6cd3f708-a126-4878-9d11-e23d27cc72b2", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.6, para 3](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ac5a8bcb-eb26-4e04-b756-0abee1b7354b", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.6, para 3](https://elifesciences.org/articles/95135)"}, "hash": "eef570b7ae190e4b40e32e4cac80cc77ba32ede36fd8642991f2ff7a184e1b4f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|gateHHtauInf|gateKS|HHExpLinearRate|\n|-|-|-|\n|HHExpLinearVariable|HHExpRate|HHExpVariable|\n|HHSigmoidRate|HHSigmoidVariable|ionChannel|\n|ionChannelHH|ionChannelKS|ionChannelPassive|\n|ionChannelVShift|KSState|KSTransition|\n|open State|q10ConductanceScaling|q10ExpTemp|\n|q10Fixed|reverse Transition|sub Gate|\n|tauInfTransition|vHalfTransition|closedState|", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 354, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "889cf7cc-73cc-4460-8fcf-ad47f39650e3": {"__data__": {"id_": "889cf7cc-73cc-4460-8fcf-ad47f39650e3", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.6, para 4](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "efff4b7c-bd16-4e61-b4c3-7701fb602b6a", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.6, para 4](https://elifesciences.org/articles/95135)"}, "hash": "959edee1a807d6b2854d12ecaa63e2f984de9fc17f4fc9f7a3aaeea94b9c09a7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "fit into a 'population' of a 'network' (**Figure 2**). To support the range of electrical properties found in biological neurons, ionic conductances with distinct ionic selectivities and dynamics can be generated in NeuroML through the inclusion of different types of gates (e.g. activation, inactivation), their dependence on variables such as voltage and \\[Ca^2+] and their reversal potential. Cell types with different functional and biophysical properties can then be generated by conferring combinations of ionic conductances on their membranes. The conductance density can be adjusted to generate the electrophysiological properties found in real neurons. In practice, many examples of ionic conductances that underlie the electrical behavior of neurons are already available in NeuroMLv2 and can simply be inserted into a cell membrane (**Figure 2**). Indeed, a model element, once defined in NeuroML, acts as a building block that may be reused any number of times within or across models. Elements such as ionic conductances, cell biophysics, cell morphologies, and cell definitions that incorporate them can be serialized in separate files and 'included' in other models (e.g. morphologies", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1199, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2b7e5d5e-2348-4245-8e8f-b160e9d50463": {"__data__": {"id_": "2b7e5d5e-2348-4245-8e8f-b160e9d50463", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.6, para 5](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "df4e5149-e1c5-4b6b-9ffd-ce6e9608cfde", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.6, para 5](https://elifesciences.org/articles/95135)"}, "hash": "d3daedb57821c8e6babbbf16a67090ba44957e076e1f513e6c02248c434fa18f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "). Such reuse of model components speeds model construction and prototyping irrespective of the simulation engine used.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 119, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "29d61b06-6e14-4212-b99b-cdef05030ea2": {"__data__": {"id_": "29d61b06-6e14-4212-b99b-cdef05030ea2", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.6, para 6](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ca2eb5a1-4afa-4a23-8bd1-b58c0418c7fe", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.6, para 6](https://elifesciences.org/articles/95135)"}, "hash": "5bae8c7e8956ebdb2fd0d1a60683d4816e8069735a881b094fef26d077fe4e05", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The defined structure of each model element and the relationships between them inform users of exactly how model elements are to be created and combined. This encourages the construction of well-structured models, reduces errors and redundancy, and ensures that FAIR principles are firmly embedded in NeuroML models and the ecosystem of tools. As we will see in the following sections, NeuroML's formal structure also enables features such as model validation prior to simulation, translation into simulation specific formats, and the use of NeuroML as a common language of exchange between different tools.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 607, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1312f2ef-3fde-4a3a-b4b5-ad36b39b592b": {"__data__": {"id_": "1312f2ef-3fde-4a3a-b4b5-ad36b39b592b", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.6, para 7](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "932de077-5d18-4584-82ea-e62005d3c0d8", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.6, para 7](https://elifesciences.org/articles/95135)"}, "hash": "a40de8b156fb210ad1b8d3efb1ba4d633c8dfed229acfb5129f5dc644ead43ff", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## NeuroML supports a large ecosystem of software tools that cover all stages of the model life cycle", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 101, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8cb114b9-d17b-4a06-b1de-7916c4b750ab": {"__data__": {"id_": "8cb114b9-d17b-4a06-b1de-7916c4b750ab", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.6, para 8](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4fe737d1-1443-41d1-bdb2-56161ad0056a", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.6, para 8](https://elifesciences.org/articles/95135)"}, "hash": "cd4a3ced27d209e690ce5cef21aa195636d8d951d80660e40e885cf08af0341a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Model building and the generation of scientific knowledge from simulation and analysis of models is a multi-step, iterative process requiring an array of software tools. NeuroML supports all stages of the model development life cycle (**Figure 1**), by providing a single model description format that interacts with a myriad of tools throughout the process. Researchers typically assemble ad-hoc sets of scripts, applications, and processes to help them in their investigations. In the absence of standardization, they must work with the specific model formats and APIs that each tool they use requires, and somehow convert model descriptions when using multiple applications in a toolchain. NeuroML addresses this issue by providing a common language for the use and exchange of models and their components between different simulation engines and modeling tools. The NeuroML ecosystem includes a large collection of software tools, both developed and maintained by the main NeuroML contributors (the 'core NeuroML tools and libraries:' jNeuroML, pyNeuroML, APIs) and those external applications that have added NeuroML support (**Figures 3 and 4a, Tables 3 and 4**).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1169, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9697410b-d70c-4913-b7bc-815a45904d3e": {"__data__": {"id_": "9697410b-d70c-4913-b7bc-815a45904d3e", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.6, para 9](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9002eeaa-3538-472e-889f-c8e4f665a55f", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.6, para 9](https://elifesciences.org/articles/95135)"}, "hash": "792f345e93de2b71a2ebd7dae54cf183f2f232768178af7e6e40272f87a1019e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The core NeuroML tools and libraries include APIs in several programming languages\u2014Python, Java, C++, and MATLAB. These tools provide critical functionality to allow users to interact with NeuroML components and build models. Using these, researchers can build models from scratch, or read, modify, analyze, visualize, and simulate existing NeuroML models on supported simulation", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 379, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6940cc5f-ccc0-4978-8610-9317c7c98848": {"__data__": {"id_": "6940cc5f-ccc0-4978-8610-9317c7c98848", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.6, para 10](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9bc9aa54-e059-4e7a-a01e-56b6be090bf7", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.6, para 10](https://elifesciences.org/articles/95135)"}, "hash": "b977735013b2a08fb29c2190e53d8121bcfb7d1d0fe9cb89c749d40283b31bd9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135 6 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 93, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d3a26b71-3662-4cac-ae4c-58a6e6ff1279": {"__data__": {"id_": "d3a26b71-3662-4cac-ae4c-58a6e6ff1279", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.7, para 1](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0dff92ca-44cf-4fb9-b77a-903e83a98eca", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.7, para 1](https://elifesciences.org/articles/95135)"}, "hash": "0dfe3d35db38e15e8232bfbf207971b8fe0b018b5756cc15ce5e2bf19c171d33", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Table 2.** Index of standard NeuroMLv2 ComponentTypes (continued).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 68, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f0f7ccb1-dddc-4b77-94e3-d471845e6bb1": {"__data__": {"id_": "f0f7ccb1-dddc-4b77-94e3-d471845e6bb1", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.7, para 2](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b8f57715-5189-4142-b31e-0e5bf7cd33e8", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.7, para 2](https://elifesciences.org/articles/95135)"}, "hash": "c2aab141791ef85a7b67d76b8c86e38c2878dfced17c7cbaa51520bfe7b53f95", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|ComponentTypes related to synapses||||\n|-|-|-|-|\n|alphaCurrentSynapse|alphaSynapse|blockingPlasticSynapse||\n|doubleSynapse|expOneSynapse|expThreeSynapse||\n|expTwoSynapse|gap Junction|gradedSynapse||\n|linearGradedSynapse|silentSynapse|stdpSynapse||\n|tsodyksMarkramDepFacMechanism|tsodyksMarkramDepMechanism|voltageConcDepBlockMechanism||\n|ComponentTypes related to inputs||||\n|compoundInput|compoundInputDL|poissonFiringSynapse||\n|pulseGenerator|pulseGeneratorDL|rampGenerator||\n|rampGeneratorDL|sineGenerator|sineGeneratorDL||\n|spike|spikeArray|spike Generator||\n|spikeGeneratorPoisson|spikeGeneratorRandom|spikeGeneratorRefPoisson||\n|timedSynapticInput|transientPoissonFiringSynapse|voltage Clamp||\n|voltageClampTriple||||\n|ComponentTypes related to networks||||\n|connection|connectionWD|continuous Connection||\n|continuousConnectionInstance|continuousConnectionInstanceW|continuous Projection||\n|electrical Connection|electricalConnectionInstance|electricalConnectionInstanceW||\n|electrical Projection|explicit Connection|explicitInput||\n|input|inputList|inputW||\n|instance|location|network||\n|networkWithTemperature|population|population List||\n|projection|rectangularExtent|region||\n|synaptic Connection|synapticConnectionWD|||\n|ComponentTypes related to model simulation||||\n|Display|EventOutputFile|EventSelection||\n|Line|OutputColumn|OutputFile||\n|Simulation||||\n|ComponentTypes related to PyNN||||\n|alphaCondSynapse|alphaCurrSynapse|EIF\\_cond\\_alpha\\_isfa\\_ista||\n|EIF\\_cond\\_exp\\_isfa\\_ista|expCondSynapse|expCurrSynapse||\n|HH\\_cond\\_exp|IF\\_cond\\_alpha|IF\\_cond\\_exp||\n|IF\\_curr\\_alpha|IF\\_curr\\_exp|SpikeSourcePoisson||", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1631, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2216858f-cf62-40bd-b094-3d29efda35c2": {"__data__": {"id_": "2216858f-cf62-40bd-b094-3d29efda35c2", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.7, para 3](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c67415b2-d156-4761-86db-8387d6334453", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.7, para 3](https://elifesciences.org/articles/95135)"}, "hash": "1fac4cc5c747d54be471fb4d8605970837dac3552bc0beceaaaedc65bd0f1f3e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "platforms. Furthermore, developers can also use the core tools, libraries, and APIs to support NeuroML in their own applications.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 129, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7c8526b8-98ba-4fe3-9ba6-3d61397cf25f": {"__data__": {"id_": "7c8526b8-98ba-4fe3-9ba6-3d61397cf25f", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.7, para 4](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "66e6e95c-2ce3-4a18-afa5-a41913442e55", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.7, para 4](https://elifesciences.org/articles/95135)"}, "hash": "ce0c50d5c24562409d2faec7ba02adefc6053323a03e5434b47874f5fd20b80d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The simulation platforms e.g. EDEN (*Panagiotou et al., 2022*), NEURON (*Hines and Carnevale, 1997*), along with other independently developed tools, form the next layer of the software ecosystem\u2014providing extra functionality such as interactive model construction (e.g. neuroConstruct *Gleeson et al., 2007*), NetPyNE (*Dura-Bernal et al., 2019*), additional visualization (e.g. OSB *Gleeson et al., 2019b*), analysis (e.g. NeuroML-DB *Birgiolas et al., 2023*), data-driven validation (e.g. SciUnit *Gerkin et al., 2019*), and archival/sharing (e.g. OSB, NeuroML-DB). Indeed, OSB and NeuroML-DB are prime examples of how advanced neuroinformatics resources can be built on top of standards such as NeuroML.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 707, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f8b70ea5-92b1-4646-a209-2197b26a5dea": {"__data__": {"id_": "f8b70ea5-92b1-4646-a209-2197b26a5dea", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.7, para 5](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4d0b4040-80df-422b-8122-95894b78ca02", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.7, para 5](https://elifesciences.org/articles/95135)"}, "hash": "9af5ddbf83612af470db5d1594d54d1dd24f1d393e3d651e87e0399d20583183", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135 7 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 93, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1c0ef9c3-e641-4f00-8c92-dcbacf04b35a": {"__data__": {"id_": "1c0ef9c3-e641-4f00-8c92-dcbacf04b35a", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.8, para 1](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "acb0c14e-d1b3-489f-84ca-771a0269a4ec", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.8, para 1](https://elifesciences.org/articles/95135)"}, "hash": "c06878a397d4c5ab1bd96a549ffaa429dd6309c021b62c5ca9c09f50df300b7e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**a.**\n\\[Diagram showing a cell membrane with ion channels and Na^+ ions passing through.]", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 90, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9f7b54d9-8736-42b7-9fe8-5646ec795b16": {"__data__": {"id_": "9f7b54d9-8736-42b7-9fe8-5646ec795b16", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.8, para 2](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0d889d93-e77e-4a6b-be9a-9bc6cc0c153c", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.8, para 2](https://elifesciences.org/articles/95135)"}, "hash": "20e4ccdec792087ba0d354276c8d3dc05f46c64ec802e07d3b9433d780a275f7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**b.**\n\\[Diagram showing two morphologically detailed neurons, one in red and one in blue.]", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 91, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "17808844-c047-4a0e-ab0c-0d9ca8921833": {"__data__": {"id_": "17808844-c047-4a0e-ab0c-0d9ca8921833", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.8, para 3](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bcee61e8-c80f-4621-ac22-a28a754c5ff0", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.8, para 3](https://elifesciences.org/articles/95135)"}, "hash": "73be6ac3b6ef87c0b02f3ed125221276ed5d0c8fec9854eb038f347cdc86071a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**c.**\n\\[Diagram showing a complex network of interconnected neurons in green, red, and blue.]", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 94, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0329fed0-b80a-4198-9b49-c0ffddaa4bd4": {"__data__": {"id_": "0329fed0-b80a-4198-9b49-c0ffddaa4bd4", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.8, para 4](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "116d3110-4fc2-4392-85bc-ae5e1bfbeded", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.8, para 4](https://elifesciences.org/articles/95135)"}, "hash": "a7aa009ea37a9142391b2d90ea1b774dcea507aad74346f77492a16acb844d23", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Conductances**\n\\[Diagram showing hierarchical blocks: gate 1, gate 2, gate 3 connected to a larger gate structure.]", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 117, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "143c7342-73c8-4b44-b70a-46ea710b0f88": {"__data__": {"id_": "143c7342-73c8-4b44-b70a-46ea710b0f88", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.8, para 5](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6b569ab2-e879-4874-a601-a4a719f7c2dc", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.8, para 5](https://elifesciences.org/articles/95135)"}, "hash": "a145718928c34980fc3eb0fab2673e47de6fcb95f94b7b85653a179c425215d8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Cells**\n\\[Diagram showing hierarchical blocks: morph1 and morph2 connected to cell structures.]", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 97, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "267e1444-8ef3-4279-8635-e242501630fd": {"__data__": {"id_": "267e1444-8ef3-4279-8635-e242501630fd", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.8, para 6](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "17008e2d-3be0-45c2-b104-6ceb784f4c8a", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.8, para 6](https://elifesciences.org/articles/95135)"}, "hash": "84caf30809eb26fc7799a1487975e5cfc7640b21a35355d653ae4055bacf9142", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Networks**\n\\[Diagram showing hierarchical blocks: pop 1, projection, and pop 2 representing network components.]", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 114, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3adf1284-52b9-4c96-8be3-40e6c84db970": {"__data__": {"id_": "3adf1284-52b9-4c96-8be3-40e6c84db970", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.8, para 8](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b6f33a31-01f2-4867-8ec9-8367f04f8591", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.8, para 8](https://elifesciences.org/articles/95135)"}, "hash": "fe901571bd8fb2c184e0b13511dcd3090efd6bb0cebe98bb47a9ebae4d722bbc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Figure 2.** NeuroML is a modular, hierarchical format that supports multi-scale modeling. Elements in NeuroML are formally defined, independent, self-contained building blocks with hierarchical relationships between them. **(a)** Models of ionic conductances can be defined as a composition of gates, each with specific voltage (and potentially \\[Ca^2+]) dependence that controls the conductance. **(b)** Morphologically detailed neuronal models specify the 3D structure of the cells, along with passive electrical properties, and reference ion channels that confer membrane conductances. **(c)** Network models contain populations of these cells connected via synaptic projections. **(d)** A truncated illustration of the main categories of the NeuroMLv2 standard elements and their hierarchies. The standard includes commonly used model elements/building blocks that have been pre-defined for users: **Cells:** neuronal models ranging from simple spiking point neurons to biophysically detailed cells with multi-compartmental morphologies and active membrane conductances; **Synapses and ionic conductance models:** commonly used chemical and electrical synapse models (gap junctions), and multiple representations for\n*Figure 2 continued on next page*", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1256, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "25515a65-e020-4d93-ad48-8bca42f4f34e": {"__data__": {"id_": "25515a65-e020-4d93-ad48-8bca42f4f34e", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.8, para 9](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d273dd1f-0ee2-4097-9896-a2b103da3d8d", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.8, para 9](https://elifesciences.org/articles/95135)"}, "hash": "6b9d8a65745a1e6a6afb539ab0dc83f74d46df181e0499e9604d3d7ae6a26471", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135 8 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 93, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "98e3a57b-9041-48d2-9cb7-719c1b5fa0ac": {"__data__": {"id_": "98e3a57b-9041-48d2-9cb7-719c1b5fa0ac", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.9, para 2](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a544a76d-16d9-44f6-8a1d-f7129bf5a5a0", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.9, para 2](https://elifesciences.org/articles/95135)"}, "hash": "cca45aa7d552ba358a32ea91449640801fd8a52d081d4b67bc323a4a5500a879", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Figure 3.** NeuroML compliant tools and their relation to the model life cycle. The inner circle shows the core NeuroML tools and libraries that are maintained by the NeuroML developers. These provide the functionality to read, modify, or create new NeuroML models, as well as to validate, analyze, visualize and simulate the models. The outermost layer shows NeuroML-compliant tools that have been developed independently to allow various interactions with NeuroML models. These complement the core tools by facilitating model creation, validation, visualization, simulation, fitting/optimization, sharing, and reuse. Further information on each of the tools shown here can be found in **Tables 3 and 4**.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 708, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6e02b869-3843-4004-8ebb-8c796149df08": {"__data__": {"id_": "6e02b869-3843-4004-8ebb-8c796149df08", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.9, para 3](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b98f6c86-de99-4cc8-88fa-be63badab8a6", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.9, para 3](https://elifesciences.org/articles/95135)"}, "hash": "b3e584f35fee7b6bb9887ef7ad854af62c319d247760462b279ffa92d667f931", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Life Cycle Stage|Core NeuroML Tools (Inner Circle)|NeuroML-compliant Tools (Outer Layer)|\n|-|-|-|\n|Create|pyNeuroMLlibNeuroMLMATLAB/C++ APIs|NetPyNEneuroConstructN2APyNNNEURON|\n|Validate|jNeuroMLpyNeuroML|SciUnitOMV|\n|Visualize|pyNeuroML|NetPyNEOSBNeuroML-DBneuroConstruct|\n|Simulate|jLEMSjNeuroMLpyNeuroML|NEURONArborNESTPyNNBrian2EDENMOOSENetPyNE|\n|Fit|pyNeuroML|NeuroTuneBluePyOptSciUnitNetPyNE|\n|Share|pyNeuroML|OSBNeuroML-DB|\n|Reuse|pyNeuroML|NeuroMorpho.OrgOSBNeuroML-DB|", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 478, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "76f0c31b-b493-49c6-ac51-61019330b55e": {"__data__": {"id_": "76f0c31b-b493-49c6-ac51-61019330b55e", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.9, para 4](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9dd83eac-9343-4b98-893b-41e55d1dce6d", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.9, para 4](https://elifesciences.org/articles/95135)"}, "hash": "88d313bb18935004c016a35ef1839ffff02ca0b3b690b725e780321969bdd37f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "***Table 5*** lists interactive, step-by-step guides in the NeuroML documentation, which can be followed to learn the fundamental NeuroML concepts, as well as illustrate how NeuroML-compliant tools can be used to achieve specific tasks across the model development life cycle. In the following sections, we discuss the specific functionality available at each stage of model development.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 387, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "099ca034-58c4-4322-a1c7-395df67328c7": {"__data__": {"id_": "099ca034-58c4-4322-a1c7-395df67328c7", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.9, para 5](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c268581c-e2e3-48e1-940c-55f917ad45b5", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.9, para 5](https://elifesciences.org/articles/95135)"}, "hash": "6b5b8f9f7a97454e1999c20e1b9c5c209540c83d64e380d49a3f69200064c7f8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Creating NeuroML models", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 26, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0d0cf4ed-d615-4411-ac92-99a8dd282626": {"__data__": {"id_": "0d0cf4ed-d615-4411-ac92-99a8dd282626", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.9, para 6](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d8998f49-4605-48f7-ad96-8d9da0b3bd77", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.9, para 6](https://elifesciences.org/articles/95135)"}, "hash": "8c61b39fb9c05babb99b6288d03b2693e37a9bff92c792aaefac1a4a13de0b6b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The structured declarative elements of NeuroMLv2, when combined with a procedural scripting language such as Python, provide a powerful and yet intuitive \u2018building block\u2019 approach to model construction. For this reason, Python is now the recommended language for interacting with NeuroML (***Figure 4***), although XML remains the primary serialization language for the format (i.e. for saving to disk and depositing in model repositories (***Figure 5***)). Python has emerged as a key programming language in science, including many areas of neuroscience (*Muller et al., 2015*). A Python-based NeuroML ecosystem ensures that users can take advantage of Python\u2019s features, and also use packages from the wider Python ecosystem in their work (e.g. Numpy (*Harris et al., 2020*), Matplotlib *Hunter, 2007*). pyNeuroML, the Python interface for working with NeuroML, is built on top of the Python NeuroML API, libNeuroML (*Vella et al., 2014; Sinha, 2023; Figure 4*).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 965, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "59dbfe41-b912-453a-b12c-850b175998d8": {"__data__": {"id_": "59dbfe41-b912-453a-b12c-850b175998d8", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.9, para 7](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5d722017-2f5a-4042-881b-31f918ea611d", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.9, para 7](https://elifesciences.org/articles/95135)"}, "hash": "e71a9ad979da262276d5c34cdfbb49b98d1b0562d91348300d83edeffb93bf8b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "As illustrated in ***Figure 5***, Python can be used to combine different NeuroML components into a model. NeuroML supports several pathways for the creation of new models. Modelers may use", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 189, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "31a4aae1-3b40-4a0a-a843-5077813b3260": {"__data__": {"id_": "31a4aae1-3b40-4a0a-a843-5077813b3260", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.9, para 8](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0fe3170c-a774-40bf-88ab-8fb95f7b9639", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.9, para 8](https://elifesciences.org/articles/95135)"}, "hash": "bc18239d354eb5951761ad7eccfd0ee08f32775ea53b0b972cba444d09a61a6b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "*Figure 2 continued*\nionic conductances; **Inputs**: to drive cell and network activity, e.g., current or voltage clamp, spiking background inputs; **Networks**: of populations (containing any of the aforementioned cell types), and projections. The full list of standard NeuroML elements can be found in ***Tables 1 and 2***.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 325, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "275f3cdc-589d-4842-aeb0-704a4f0093d5": {"__data__": {"id_": "275f3cdc-589d-4842-aeb0-704a4f0093d5", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.9, para 9](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2b9d9ec8-8914-42df-99e6-b2b1e24be6cc", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.9, para 9](https://elifesciences.org/articles/95135)"}, "hash": "2f3a6c4a87395e3b3b404f024ec87fda48b78c263b55ccd006a561247532f732", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135 9 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 93, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fdc72878-6ac4-4abb-9de9-ac6aa7ff1a83": {"__data__": {"id_": "fdc72878-6ac4-4abb-9de9-ac6aa7ff1a83", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.10, para 3](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "75b8ea2c-b710-41cc-9490-0b22883d477a", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.10, para 3](https://elifesciences.org/articles/95135)"}, "hash": "4ea7692f826587f270c47e28ab7a914bfd794580368f23f2dd66319636171909", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "```python\nfrom neuroml import * # NeuroML API libNeuroML\n\nnewdoc = NeuroMLDocument(id=\"new_doc\")\nnewcell = IafTauCell(id=\"cell_0\",\n    leak_reversal=\"-60mV\", thresh=\"0mV\",\n    tau=\"5ms\", reset=\"-70mV\")\nnewdoc.add(newcell)\n\nnetwork = newdoc.add(Network, id=\"new_net\",\n    validate=False)\npopulation = network.add(Population,\n    id=\"new_pop\", size=10,\n    component=newcell.id)\n\n# Helper method to ensure all parameters\n# present and appropriate\nnewdoc.validate(recursive=True)\n```", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 480, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fdd036fa-4cf0-499e-aed0-b0b52c414190": {"__data__": {"id_": "fdd036fa-4cf0-499e-aed0-b0b52c414190", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.10, para 6](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8718339a-9b80-49e9-90b2-3b24516ca87d", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.10, para 6](https://elifesciences.org/articles/95135)"}, "hash": "46696da26a9f5cfb1c628fc96ff27d146ce056081b97bf74efe7153624419ef0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Figure 4.** The core NeuroML software stack, and an example NeuroML model created using the Python NeuroML tools. **(a)** The core NeuroML software stack consists of Java (blue) and Python (orange) based applications/libraries, and the LEMS model ComponentType definitions (green), wrapped up in a single package, pyNeuroML. Each of these modules can be used independently or the whole stack can be obtained by installing pyNeuroML with the default Python package manager, Pip: `pip install pyneuroml`. **(b)** An example of how to create a simple NeuroML model is shown, using the NeuroMLv2 Python API (libNeuroML) to describe a model consisting of a population of 10 integrate and fire point neurons (IafTauCell) in a network. The IafTauCell, Network, Population, and NeuroMLDocument model ComponentTypes are provided by the NeuroMLv2 standard. The underlying dynamics of the model are hidden from the user, being specified in the LEMS ComponentType definitions of the elements (see Methods). The simulator-independent NeuroML model description can be simulated on any of the supported simulation engines. **(c)** Extensible Markup Language (XML) serialization of the NeuroMLv2 model description shows the correspondence between the Python object model and the XML serialization.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1283, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f8633de6-8ee4-4827-965d-a6c9956b2cb7": {"__data__": {"id_": "f8633de6-8ee4-4827-965d-a6c9956b2cb7", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.10, para 7](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "349cdc9f-b883-4444-9ce9-a541995607a5", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.10, para 7](https://elifesciences.org/articles/95135)"}, "hash": "ce0c92a84fc9960f58f4d27a63683328f288155da111c50eced5b3f7dc12b913", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135\n10 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 94, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "76115e00-9790-460d-b038-03ba9d1d1202": {"__data__": {"id_": "76115e00-9790-460d-b038-03ba9d1d1202", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.11, para 1](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8e9ace47-af8d-4627-b888-8ea193901f94", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.11, para 1](https://elifesciences.org/articles/95135)"}, "hash": "bd5b80967333d8f99188dee73b3bd3dba87d75e315486367f877eb6f2f1622a9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Table 3.** NeuroML software core tools and libraries, with a description of their scope, the main programming language they use (or other interaction means, e.g. Command Line Interface (CLI)), and links for more information.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 226, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c20ecb9e-b5d9-485d-8e5d-575dbac3c4aa": {"__data__": {"id_": "c20ecb9e-b5d9-485d-8e5d-575dbac3c4aa", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.11, para 2](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "663e22a3-3799-4a7e-bc91-052f8f747822", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.11, para 2](https://elifesciences.org/articles/95135)"}, "hash": "5903785ab16517801d3ad8a1a551bd0c32a2d592dba0ea0877738b1231d10d8e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Tool|Language/interface|Description|URL|\n|-|-|-|-|\n|pyNeuroML|Python/CLI|Recommended Python library for NeuroML; provides pynml, primary command line tool for NeuroML|https://docs.neuroml.org/Userdocs/Software/pyNeuroML.html|\n|libNeuroML|Python|Python API for NeuroML|https://docs.neuroml.org/Userdocs/Software/libNeuroML.html|\n|NeuroMLlite|Python|High level library for creating NeuroML network models (beta)|https://docs.neuroml.org/Userdocs/Software/NeuroMLlite.html|\n|PyLEMS|Python/CLI|Python API and simulator for LEMS|https://docs.neuroml.org/Userdocs/Software/pyLEMS.html|\n|jLEMS|Java/CLI|Java API for LEMS and reference simulator|https://docs.neuroml.org/Userdocs/Software/jLEMS.html|\n|org.neuroml.model|Java|Java API for NeuroML, DOI:10.5281/zenodo.5783290|https://github.com/NeuroML/org.neuroml.model/|\n|org.neuroml.export|Java|Java API for translating NeuroML into different formats such as NEURON, DOI:10.5281/zenodo.1346272|https://github.com/NeuroML/org.neuroml.export|\n|org.neuroml.import|Java|Java API for importing formats into LEMS and NeuroML, DOI:10.5281/zenodo.5783295|https://github.com/NeuroML/org.neuroml.import|\n|jNeuroML|Java/CLI|Wraps jLEMS and all export/import packages and provides the jnml tool, DOI:10.5281/zenodo.593108|https://docs.neuroml.org/Userdocs/Software/jNeuroML.html|\n|NeuroML-C++|C++|C++ API for NeuroML|https://docs.neuroml.org/Userdocs/Software/NeuroML\\_API.html|\n|NeuroML Toolbox|MATLAB|MATLAB NeuroML Toolbox|https://docs.neuroml.org/Userdocs/Software/MatLab.html|", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1513, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "042a56ca-866f-4f68-b5e1-e303f6e52c05": {"__data__": {"id_": "042a56ca-866f-4f68-b5e1-e303f6e52c05", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.11, para 3](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c13d59e3-3ac1-412d-ae45-b1e5b6ec13e4", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.11, para 3](https://elifesciences.org/articles/95135)"}, "hash": "976259836e63350a57975e84b33d433f4e94655f49ad61f4888270c233ef75f3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "elements included in the NeuroML standard, re-use user-defined NeuroML model elements from other models, or define completely new model elements using LEMS (**Figure 5**) (see section on extending NeuroML below). It is common for models to use a combination of these strategies, e.g., *Gurnani and Silver, 2021; Kriener et al., 2022; Cayco-Gajic et al., 2017*, highlighting the flexibility provided by the modular design of NeuroML. NeuroML APIs support all of these workflows. The Python tools also include many additional higher-level utilities to speed up model construction, such as factory functions, type hints, and convenience functions for building complex multi-compartmental neuron models (**Figure 6**).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 714, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b6ff0ba1-f338-4e32-a9f5-13c7f4d7a6d2": {"__data__": {"id_": "b6ff0ba1-f338-4e32-a9f5-13c7f4d7a6d2", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.11, para 4](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cdfc914a-7df5-4e23-9adb-cd3212443369", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.11, para 4](https://elifesciences.org/articles/95135)"}, "hash": "6ccf3101c8ab2176e6714f449e90eff1e800e9e095e97fa1c76b37ff18eee42f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "For the construction of complex 3D circuit models, or for users who are not experienced with Python, a range of NeuroML-compliant online and standalone applications with graphical user interfaces are available. These include NetPyNE's interactive web interface (*Dura-Bernal et al., 2019*) (which is available on the latest version of OSB (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 340, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "babe5a54-cca5-4608-872b-78175222f323": {"__data__": {"id_": "babe5a54-cca5-4608-872b-78175222f323", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.11, para 5](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9107342e-1f4a-47fd-9048-6b76d3e45eb3", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.11, para 5](https://elifesciences.org/articles/95135)"}, "hash": "f950dc5357ef6d2427cbd9911e971eb3feb100de1cafe47b294b83ee851edbb0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ")) and neuroConstruct (*Gleeson et al., 2007*) which can export models directly into NeuroML and LEMS. These applications can be used to build and simulate new NeuroML models without requiring programming. Thus, users can take advantage of the individual features provided by these applications to generate NeuroML-compliant models and model elements.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 351, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "072c7ba1-5c67-40f1-b2aa-d69452af386f": {"__data__": {"id_": "072c7ba1-5c67-40f1-b2aa-d69452af386f", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.11, para 6](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "08db20db-ba30-438c-b54f-b883801aeb81", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.11, para 6](https://elifesciences.org/articles/95135)"}, "hash": "09191abc12a0fd4b11072916a40f3a34bdefa39478c4897d5c4115aed06ac4e2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Validating NeuroML models", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 28, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5372771d-e468-4599-96bc-9faffec62433": {"__data__": {"id_": "5372771d-e468-4599-96bc-9faffec62433", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.11, para 7](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ca05c2f4-d7f0-44f3-b1ab-bef4da057c55", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.11, para 7](https://elifesciences.org/articles/95135)"}, "hash": "80ae6c104dfe98b26a445d96131ea0694e8475ff26c86f52cd23da273d16f30d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Ensuring a model is 'valid' can have different meanings at different stages of the life cycle\u2014from checking whether the source files are in the correct format, to ensuring the model reproduces a significant feature of its biological counterpart. NeuroML's hierarchical, well-defined structure allows users to check their model descriptions for correctness at multiple levels (**Figure 7**), in a manner similar to", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 413, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4d04a91c-eb62-451e-94e9-eeb6e72e96d6": {"__data__": {"id_": "4d04a91c-eb62-451e-94e9-eeb6e72e96d6", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.11, para 8](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ef4b793a-d631-42f9-ac4f-f5ef811230f1", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.11, para 8](https://elifesciences.org/articles/95135)"}, "hash": "0197dfb45e1873bddeefb17b9149f319fcedabcde8cbab1ef559b8908a93b3f7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135 11 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 94, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6fbbc009-b7cf-4fe7-9bcd-fe49bc19bba6": {"__data__": {"id_": "6fbbc009-b7cf-4fe7-9bcd-fe49bc19bba6", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.12, para 1](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "80c73906-fa86-4e8a-9376-072d46e50166", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.12, para 1](https://elifesciences.org/articles/95135)"}, "hash": "01b874de75e3a8008cb0b30f123418f9f5f549476b3720503e3138fbe05e9835", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Table 4.** Tools in the wi main programming language they use (or other interaction means, e.g. through a web browser, Graphical User Interface (GUI) or Command Line Interface (CLI)), and links for more information.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 217, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d22bfd2d-29ce-47e3-b000-f0560614a22c": {"__data__": {"id_": "d22bfd2d-29ce-47e3-b000-f0560614a22c", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.12, para 2](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bb87d1c3-3936-49e8-a5bc-36d1c8f44f7e", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.12, para 2](https://elifesciences.org/articles/95135)"}, "hash": "835695f0b4f2e3798ca77cfc7cd9aecffa2d6db9051eca34a67b786f3837ab5f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Tool|Language/interface|Description|URL|\n|-|-|-|-|\n|Simulation engines||||\n|NEURON|Python/Hoc/CLI/GUI|Empirically-based simulations of neurons and networks of neurons|https://docs.neuroml.org/Userdocs/Software/Tools/NEURON.html|\n|NetPyNE|Python/web|Package to facilitate the development, parallel simulation, analysis, and optimization of biological neuronal networks using the NEURON simulator. Also has a graphical web interface, NetPyNE-UI|https://docs.neuroml.org/Userdocs/Software/Tools/NetPyNE.html|\n|EDEN|NeuroML|NeuroML-based neural simulator|https://docs.neuroml.org/Userdocs/Software/Tools/EDEN.html|\n|MOOSE|Python|The Multiscale Object-Oriented Simulation Environment is the base and numerical core for large, detailed multi-scale simulations that span computational neuroscience and systems biology. Based on a reimplementation of the GENESIS 2 core.|https://docs.neuroml.org/Userdocs/Software/Tools/MOOSE.html|\n|PyNN|Python|A simulator-independent language for building neuronal network models|https://docs.neuroml.org/Userdocs/Software/Tools/PyNN.html|\n|NEST|Python/SLI|Simulator for spiking neural network models focusing on dynamics, size, and structure of neural systems|https://docs.neuroml.org/Userdocs/Software/Tools/NEST.html|\n|Brian2|Python|Easy to learn and use simulator for spiking neural networks|https://docs.neuroml.org/Userdocs/Software/Tools/Brian.html|\n|Arbor|Python|A multi-compartment neuron simulation library|https://docs.neuroml.org/Userdocs/Software/Tools/Arbor.html|\n|N2A|Java/GUI|Language and IDE for writing and simulating models|https://docs.neuroml.org/Userdocs/Software/Tools/N2A.html|\n|Databases||||\n|OSB|Web|Resource for sharing and collaboratively developing computational models of neural systems|https://www\\.opensourcebrain.org/|\n|NeuroML-DB|Web|NeuroML database of cell and channel models|https://neuroml-db.org/|\n|Other tools||||\n|OMV|Python|Open Source Brain Model Validation framework|https://github.com/OpenSourceBrain/osb-model-validation|\n|SciUnit|Python|Data driven unit testing framework|https://github.com/scidash/sciunit|\n|BluePyOpt|Python|Blue Brain Python Optimization Library|https://bluepyopt.readthedocs.io/|\n|NeuroTune|Python|Package for fitting/optimization of NeuroML models|https://github.com/NeuralEnsemble/neurotune|\n|PyElectro|Python|Electrophysiology analysis package|https://github.com/NeuralEnsemble/pyelectro|", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2386, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "409232e6-1ca7-4f23-9cef-bb930a2ff07d": {"__data__": {"id_": "409232e6-1ca7-4f23-9cef-bb930a2ff07d", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.12, para 3](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6729b347-77f4-43e8-aa2e-1a0f4fec4740", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.12, para 3](https://elifesciences.org/articles/95135)"}, "hash": "0df73cb1d967a6e88051c8a468c9020734bf1a9ec622a4c541057fc7aa6ea93d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135 12 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 94, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9ab8c7be-1862-4556-b55f-4e7e9e6dc14e": {"__data__": {"id_": "9ab8c7be-1862-4556-b55f-4e7e9e6dc14e", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.13, para 1](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "21a1cf10-383a-4d5a-967c-ebc25cbfc463", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.13, para 1](https://elifesciences.org/articles/95135)"}, "hash": "89156882b931e9b64ddf75d73decb4007e5f8a2fdb2dc4ad2573c387ecd0c80f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Table 5.** Step-by-step guides for using NeuroML illustrating the various stages of the model development life cycle.\nThese include Introductory guides aimed at teaching the fundamental NeuroML concepts, Advanced guides illustrating specific modeling workflows, and Walkthrough guides discussing the steps required for converting models to NeuroML. An updated list is available at", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 382, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "11b33abd-717d-4f75-a544-33a745eeeb91": {"__data__": {"id_": "11b33abd-717d-4f75-a544-33a745eeeb91", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.13, para 2](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a73ad86c-7b43-4c33-8e1b-5625721c078c", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.13, para 2](https://elifesciences.org/articles/95135)"}, "hash": "15a7659420d8f0f21b868505fb663af7c64800c14b76c0c924799094b6374e29", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ".", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8e22d7ea-3fc1-41fd-b9b9-5240525b5483": {"__data__": {"id_": "8e22d7ea-3fc1-41fd-b9b9-5240525b5483", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.13, para 3](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f22f567e-2389-4b4d-ad71-adafd35c396b", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.13, para 3](https://elifesciences.org/articles/95135)"}, "hash": "928498f92578323c20ae55326e2a405ceeb1dbb9a883b53d6a9a9cdeef993492", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Link|Description|Model life cycle stages|\n|-|-|-|\n|Introductory guides|||\n|Guide 1|Create and simulate a simple regular spiking Izhikevich neuron in NeuroML|Create, Validate, Simulate|\n|Guide 2|Create a network of two synaptically connected populations of Izhikevich neurons|Create, Validate, Visualize, Simulate|\n|Guide 3|Build and simulate a single compartment Hodgkin-Huxley neuron|Create, Validate, Visualize, Simulate|\n|Guide 4|Create and simulate a multi compartment hippocampal OLM neuron|Create, Validate, Visualize, Simulate|\n|Advanced guides|||\n|Guide 5|Create novel NeuroML models from components on NeuroML-DB|Reuse, Create, Validate, Simulate|\n|Guide 6|Optimize/fit NeuroML models to experimental data|Create, Validate, Simulate, Fit|\n|Guide 7|Extend NeuroML by creating a novel model type in LEMS|Create, Simulate|\n|Walkthroughs|||\n|Guide 8|Guide to converting cell models to NeuroML and sharing them on Open Source Brain|Create, Validate, Simulate, Share|\n|Guide 9|Conversion of \\*Ray et al., 2020\\*|Create, Validate, Visualize, Simulate, Share|", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1061, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3a07c05a-478d-47fc-ae93-52327b894c21": {"__data__": {"id_": "3a07c05a-478d-47fc-ae93-52327b894c21", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.13, para 4](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "db7f2ee0-5e8c-41af-afa5-224bd7fe5b72", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.13, para 4](https://elifesciences.org/articles/95135)"}, "hash": "cc63fb13130237b5e221682bdab9fecc8671d8e40c0ad1728dddf9b9a5675067", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "multi-level testing in software development. Importantly, most of the validation tests in NeuroML are run on the models\u2019 NeuroML descriptions *prior to simulation*.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 164, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "57e4baeb-773f-46fd-b8d8-c64c2378f6f2": {"__data__": {"id_": "57e4baeb-773f-46fd-b8d8-c64c2378f6f2", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.13, para 5](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "16c89e67-33c6-4459-bfa8-c691edb8bb67", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.13, para 5](https://elifesciences.org/articles/95135)"}, "hash": "4f341e6d263f7c24b488dd0792b6547e085cfe12c4d662b49c68528c13a56688", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "A first level of validation checks the structure of individual model elements against their formal specifications contained in the NeuroML standard. The standard includes information on the parameters of each model element, restrictions on parameter values, their allowed units, their cardinality, and the location of the model element in the model hierarchy\u2014i.e., parent/children relationships. A second level of validation includes a suite of semantic and logical checks. For example, at this level, a model of a multi-compartmental cell can be checked to ensure that all segments referenced in segment groups (e.g. the group of dendritic segments) have been defined, and only defined once with unique identifiers. A list of validation tests currently included in the NeuroML core tools can be found in **Table 6**. These can be run against NeuroML files at the command line or programmatically in Python (**Figure 6**).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 922, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e27d7f6b-dacc-4197-a082-44b0178b5ad1": {"__data__": {"id_": "e27d7f6b-dacc-4197-a082-44b0178b5ad1", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.13, para 6](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "80ff7f9b-1460-4901-b61e-2c781eb09044", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.13, para 6](https://elifesciences.org/articles/95135)"}, "hash": "c80362d48e96b107942ac3700bc9c77772954f2a3cab895fc54ec72a3878aaa7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "A key advantage of using the NeuroML2/LEMS framework is that dimensions and units are inbuilt into LEMS descriptions. This enables automated conversions of units, unit checking, together with the validation of equations. Any expressions in models which are dimensionally inconsistent will be highlighted at this stage. Note that LEMS handles unit conversions internally\u2014modelers have flexibility in how they enter the *units* of parameter values (e.g. specifying conductance density in S/m^2 or mS/cm^2) in the NeuroML files, with the underlying LEMS definitions ensuring that a consistent set of dimensions are used in model equations (**Cannon et al., 2014**). LEMS then takes care of mapping the entered units to the target simulator\u2019s preferred units. This makes model definition, inspection, use, extension, and translation easier and less error-prone.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 857, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9c76962a-87a5-47c5-80e1-79bca94b6a89": {"__data__": {"id_": "9c76962a-87a5-47c5-80e1-79bca94b6a89", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.13, para 7](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8ef75cc3-ed11-4e26-8394-ba8dcea590f0", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.13, para 7](https://elifesciences.org/articles/95135)"}, "hash": "c1592ba6679fac7326a110620b92558f71046a31d975f1d6591c899bb776e9e2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Once the set of NeuroML files are validated, the model can be simulated, and checks can be made to test whether execution produces consistent results (e.g. firing rate of neurons in a given population) across multiple simulators (or versions of the same simulator). For this, the OSB Model Validation (OMV) framework has been developed (**Gleeson et al., 2019b**). This framework can automatically check that the output (e.g. spike times) of a NeuroML model running on a given simulator is within an allowed tolerance of the expected value. OMV has been applied to NeuroML models that have been shared on OSB, to test consistent behavior of models as the models themselves, and all supported", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 691, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "720727a1-0f9a-40ed-bf35-46bdf1538582": {"__data__": {"id_": "720727a1-0f9a-40ed-bf35-46bdf1538582", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.13, para 8](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2b977dae-58f2-4f56-af62-bf6bca110d4b", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.13, para 8](https://elifesciences.org/articles/95135)"}, "hash": "a0b2489f9c30f472e99e41c574888921bb0c8976394aa84065bd40bd5d2b3b3b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135 13 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 94, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "37112cb0-8545-4121-aa70-25894974c602": {"__data__": {"id_": "37112cb0-8545-4121-aa70-25894974c602", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.14, para 1](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a63d938c-a7c6-4d4c-b696-aa186d6c2d5e", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.14, para 1](https://elifesciences.org/articles/95135)"}, "hash": "cbda003a38b51847f6a6c7245e64e14d4c01b2e25378d368b733b6867368adb7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Figure 5.** Workflow showing how to create and simulate NeuroML models using Python. The Python API can be used to create models which may include elements built from scratch from the NeuroML standard, re-use elements from previously created models, or create new components based on novel model definitions expressed in LEMS (red). The generated model elements are saved in the default XML-based serialization (blue). The NeuroML core tools and libraries (orange) include modules to import model descriptions expressed in the XML serialization, and support multiple options for how simulators can execute these models (green). These include: (1) execution of the NeuroML models by reference simulators; (2) execution by other independently developed simulators that natively support NeuroML, such as EDEN; (3) generation of Python \u2018import scripts\u2019 which allow NeuroML models to be imported (and converted to internal formats) by simulators which support this; (4) fully expanding the LEMS description of the models, which can be mapped to generated simulator specific scripts for target simulators; (5) mapping to other standardized formats in neuroscience and systems biology.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1180, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4a3b3219-a5e7-4b5f-a64a-13e50c09ba0e": {"__data__": {"id_": "4a3b3219-a5e7-4b5f-a64a-13e50c09ba0e", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.14, para 2](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4d2945f1-4ecc-4fc1-925b-491bbe480688", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.14, para 2](https://elifesciences.org/articles/95135)"}, "hash": "3fa1244606006e1e9f262398df2ee4c15fd044e5096f0b0e6fdd9b85cb817ffa", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "simulators, are updated. This has proven to be a valuable process for ensuring uniform usage and interpretation of NeuroML across the ecosystem of supporting tools.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 164, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c14c8ddd-4b10-48b3-bb1d-7a36e6b443c0": {"__data__": {"id_": "c14c8ddd-4b10-48b3-bb1d-7a36e6b443c0", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.14, para 3](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f6e07ef7-1ab7-4cd0-a1ef-7a88d5caf825", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.14, para 3](https://elifesciences.org/articles/95135)"}, "hash": "758834b37d2239173c7bb85424495a211d021464b3bafb69b67f772beda96ce6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "A final level of validation concerns checking whether the model elements have emergent features that are in line with experimentally observed behavior of the biological equivalents. NeuronUnit (*Gerkin et al., 2019*), a SciUnit (*Omar et al., 2014*) package for data-driven unit testing and validation of neuronal and ion channel models, is also fully NeuroML compliant, and also supports automated validation of NeuroML models shared on NeuroML-DB and OSB.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 457, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a8a2a215-f3e4-40d3-b9f3-184e5ef4ee29": {"__data__": {"id_": "a8a2a215-f3e4-40d3-b9f3-184e5ef4ee29", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.14, para 4](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "66e7a7c8-aaac-4e8c-92fc-cd60ea673784", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.14, para 4](https://elifesciences.org/articles/95135)"}, "hash": "eb8defbfcf213ada94345f41b170818dc00c26ee63b012df25e5112df2dde31a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Visualizing/analyzing NeuroML models", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 39, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "66d55d7f-1165-409d-90ef-ff4e14757d55": {"__data__": {"id_": "66d55d7f-1165-409d-90ef-ff4e14757d55", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.14, para 5](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e49b1500-3b94-4055-8e6f-84358a49ab1d", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.14, para 5](https://elifesciences.org/articles/95135)"}, "hash": "770349e0c9509262d1d423961474f58bc84aeb31cb7e04e151491d3be356394d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Multiple visualization, inspection, and analysis tools are available in the NeuroML software ecosystem. Since NeuroML models have a fixed, well-defined structure, NeuroML libraries can extract all information from their descriptions. This information can be used by modelers and their programs/tools to run automated programmatic analyses on models.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 349, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "30a69d0d-70e2-4512-b748-6a8053b690ff": {"__data__": {"id_": "30a69d0d-70e2-4512-b748-6a8053b690ff", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.14, para 6](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d1b6e640-b493-4d94-9916-613ffff6d85d", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.14, para 6](https://elifesciences.org/articles/95135)"}, "hash": "8fb11c0987ad97666dfe03548d7cbfa4b3be194e0752b85934d4e4b410efe11b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "pyNeuroML includes a range of ready-made inspection utilities for users (*Figure 6*) that can be used via Python scripts, interactive Jupyter Notebooks, and command line tools. Examining the structure of cell and network models with 2D and 3D views is important for manual validation and to compare them to their biological counterparts. Graphical views of cell model morphology and the 3-dimensional network layout (*Figure 8*), population and connectivity matrices/graphs at different levels (*Figure 9*), and model summaries can all be generated (*Figure 10*). In addition to these inspection functions, a", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 608, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "13e8b6fc-88bb-4d1f-a666-1a3fde4dd917": {"__data__": {"id_": "13e8b6fc-88bb-4d1f-a666-1a3fde4dd917", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.14, para 7](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "804daa4c-79fd-435d-bee7-99560b7253d8", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.14, para 7](https://elifesciences.org/articles/95135)"}, "hash": "0536e6356e5b4980895b4c53f83047c97849f0b7debaa7872ce16a77d83028d2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135 14 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 94, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fa40a483-af5b-43b4-8f06-e77d80d9522f": {"__data__": {"id_": "fa40a483-af5b-43b4-8f06-e77d80d9522f", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.15, para 1](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d3040292-ef8a-4717-8b6f-c7f2db0d7864", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.15, para 1](https://elifesciences.org/articles/95135)"}, "hash": "a2d7a1e11922a74bfc13726bd0e17aeab7953001b6e762f808688dfb6a7046b3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Create (using Python API)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 29, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d6da7635-d48b-4251-b52a-66a3a15cc44c": {"__data__": {"id_": "d6da7635-d48b-4251-b52a-66a3a15cc44c", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.15, para 2](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bfb1fd29-dc4f-43fb-bd50-4be3985f5540", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.15, para 2](https://elifesciences.org/articles/95135)"}, "hash": "27eb50e4f67c215a58868b61eae7a35d4d4352956b4ebb251c538e35ae1f009d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "```python\nfrom neuroml import *\n\n# Create a container document\ndoc = NeuroMLDocument(id=\"network0\")\n\n# Add single exponential synapse model\nsyn0 = doc.add(\"ExpOneSynapse\", id=\"syn0\", gbase=\"65nS\", erev=\"0mV\", tau_decay=\"3ms\")\n\n# Reuse existing ion channel model\ndoc.add(\"IncludeType\", href=\"Na_chan.channel.nml\")\n\n# Create a cell with 3D morphology using the Cell ComponentType\ncell = doc.add(\"Cell\", id=\"olm\", neuro_lex_id=\"NLXCELL:091206\") # Hippocampal CA1 OLM cell\ncell.set_init_memb_potential(\"-67mV\")\ncell.set_resistivity(\"0.15 kohm_cm\")\ncell.add_channel_density(doc, cd_id=\"na_all\", cond_density=\"10 mS_per_cm2\",\n                         ion_channel=\"Na_chan\", ion_chan_def_file=\"Na.channel.nml\",\n                         erev=\"50mV\", ion=\"na\")\ncell.add_unbranched_segment_group(\"soma_group\")\nsoma_0 = cell.add_segment(prox=[0, 0, 0, 10], dist=[0, 10, 0, 10], name=\"Seg0_soma_0\",\n                          group_id=\"soma_group\", seg_type=\"soma\")\n```", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 956, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "79ba775c-f1c3-4d25-b52b-178c6afee4c4": {"__data__": {"id_": "79ba775c-f1c3-4d25-b52b-178c6afee4c4", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.15, para 3](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "97ba9c45-8204-48ab-b539-edc3afe5e27a", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.15, para 3](https://elifesciences.org/articles/95135)"}, "hash": "0dd8ccaa6057649e33b2bf6a611da9bc89dfa4e07e49b0da70d9e5af9f58fd35", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|API examples|Command line usage examples|\n|-|-|\n|Validate||\n|validate\\_neuroml2(\"file.nml\")|> pynml \"file.nml\" -validate|\n|doc.validate(recursive=True)||\n|Inspect and visualize||\n|element.info()||\n|summary(doc)|> pynml-summary \"file.nml\"|\n|nml2\\_to\\_png(doc)|> pynml -png \"file.nml\"|\n|nml2\\_to\\_svg(doc)|> pynml -svg \"file.nml\"|\n|generate\\_nmlgraph(doc)|> pynml \"file.nml\" -graph|\n||> pynml \"file.nml\" -matrix 1|\n|plot\\_2D(cell)|> pynml-plotmorph \"cell.nml\"|\n|plot\\_interactive\\_3d(cell)|> pynml-plotmorph -interactive3d \"cell.nml\"|\n|plot\\_interactive\\_3d(network)|> pynml-plotmorph -interactive3d \"net.nml\"|\n||> pynml-channelanalysis \"channel.nml\"|\n|plot\\_channel\\_densities(cell)|> pynml-plotchan \"cell.nml\"|\n|Simulate||\n|run\\_lems\\_with\\_jneuroml(\"sim.xml\")|> pynml \"sim.xml\"|\n|run\\_lems\\_with\\_jneuroml\\_neuron(\"sim.xml\")|> pynml \"sim.xml\" -neuron -run|\n|run\\_lems\\_with\\_jneuroml\\_netpyne(\"sim.xml\")|> pynml \"sim.xml\" -netpyne -run|\n|run\\_on\\_nsg(\"jneuroml\\_neuron\", \"sim.xml\")||\n|...||\n|Share and archive||\n|create\\_combine\\_archive(\"sim.xml\")|> pynml-archive \"neuron.cell.nml\"|", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1085, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8dad50ae-d202-4332-8c46-5d426a177cd0": {"__data__": {"id_": "8dad50ae-d202-4332-8c46-5d426a177cd0", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.15, para 4](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ac8f1f64-7299-4485-95f9-a3fafe48e0dc", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.15, para 4](https://elifesciences.org/articles/95135)"}, "hash": "b7d0a455a1a82d5b7f5afc1f77b590cd3361e925751ba3fce9ad5756e181400c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Figure 6.** PyNeuroML provides Python functions and command line utilities supporting all stages of the model life cycle.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 123, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3ae5aea6-bc5e-4e60-a78a-eb41c58e2ce9": {"__data__": {"id_": "3ae5aea6-bc5e-4e60-a78a-eb41c58e2ce9", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.15, para 5](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "366897ad-8c88-4bb2-8ee5-0fbde72adfd8", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.15, para 5](https://elifesciences.org/articles/95135)"}, "hash": "15f93ebbd9064fe9633d69f69248cc3261528dc3709ec030b831c0d0d9eae93c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135 15 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 94, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c892d44a-4f86-4a23-b9ff-ab9fee7903ae": {"__data__": {"id_": "c892d44a-4f86-4a23-b9ff-ab9fee7903ae", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.16, para 1](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a82dd6df-9a5a-41ab-bd7c-b325ba477f60", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.16, para 1](https://elifesciences.org/articles/95135)"}, "hash": "0fb2b3985a2c212c7a543ceae2d4835b09bbededc8c0383f64df981360fff1a8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Figure 7.** NeuroML model development incorporates multi-level validation of models. Checks are performed on the model descriptions (blue) before simulation using validation at both the NeuroML and LEMS levels (green). After the models are simulated (yellow), further checks can be run to ensure the output is in line with expected behavior (brown). The OSB Model Validation (OMV) framework can be used to ensure consistent behavior across simulators, and comparisons can be made of model activity to their biological equivalents using SciUnit.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 546, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "51eefbbb-84fb-47c5-92c9-56c0c8be0bfa": {"__data__": {"id_": "51eefbbb-84fb-47c5-92c9-56c0c8be0bfa", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.16, para 2](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ab17edf6-effc-4021-8a47-cdf4dc846258", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.16, para 2](https://elifesciences.org/articles/95135)"}, "hash": "b7abbb12e38bd43a8f2aad5a164f49fd94733935b0ac24ed7513dab00e56af22", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "variety of utilities for the inspection of NeuroML descriptions of electrophysiological properties of membrane conductances and their spatial distribution over the neuronal membrane are also provided (*Figure 10*).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 214, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "feee8a72-12e9-45de-8eae-71d030525422": {"__data__": {"id_": "feee8a72-12e9-45de-8eae-71d030525422", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.16, para 3](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "036cc87c-6f8a-4b7a-9e4c-2271605a6b7a", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.16, para 3](https://elifesciences.org/articles/95135)"}, "hash": "e647f80c6fd5c9eb4de55674b105b6b334e5ce51ae5af32581c801134398cba8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The graphical applications included in the NeuroML ecosystem (e.g. neuroConstruct, NeuroML-DB, OSB (v1 \\[", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 105, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e5ee6702-6a7c-415c-b0b9-62cce45239ad": {"__data__": {"id_": "e5ee6702-6a7c-415c-b0b9-62cce45239ad", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.16, para 4](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "19c952de-4e7f-4887-9185-f96cb33d981f", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.16, para 4](https://elifesciences.org/articles/95135)"}, "hash": "7843dcede3e17229bdd1f78f68a15670c2ded1c8f48196359e604250c914523e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "] and v2), NetPyNE, and Arbor-GUI) also provide many of their own analysis and visualization functions. OSBv1, for example, supports automated 3D visualization of networks and cell morphologies, network connectivity graphs and metrics, and advanced model inspection features (*Gleeson et al., 2019b; Figure 8b*). On OSBv2, NetPyNE provides advanced graphical plotting and analysis facilities (*Figure 8c*). A complete JupyterLab (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 430, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "dd532ce6-6eba-4761-b72c-286661fc5681": {"__data__": {"id_": "dd532ce6-6eba-4761-b72c-286661fc5681", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.16, para 5](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "17abcc68-2a74-44ae-8578-41a14b2fc4d9", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.16, para 5](https://elifesciences.org/articles/95135)"}, "hash": "5126b475ead40ad4d90d672827237d6e7a0101323b638df4d5b2f47828b11b31", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ") interface is also included in OSBv2 for Python scripting, allowing interactive notebooks to be created and shared, mixing scripting and graphical elements, including those generated by pyNeuroML. NeuroML-DB also provides information on electrophysiology, morphology, and the simulation aspects of neuronal models (*Birgiolas et al., 2023; Figure 10a*). In general, any NeuroML-compliant application can be used to inspect and analyze elements of NeuroML models, each having their own distinct advantages.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 506, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "67dd5a50-4033-498d-bca9-7764520511be": {"__data__": {"id_": "67dd5a50-4033-498d-bca9-7764520511be", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.16, para 6](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c489dfc6-ec97-449c-b5ec-4389a6d6464a", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.16, para 6](https://elifesciences.org/articles/95135)"}, "hash": "2b5283ed6d22d7269d460939a8ec7df62c58da94007bada52047c3db81e8e17b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Simulating NeuroML models", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 28, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e464d325-1902-4fa5-a62d-5897db3271fd": {"__data__": {"id_": "e464d325-1902-4fa5-a62d-5897db3271fd", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.16, para 7](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cf255cbd-f756-4eb8-b2d8-f53b0802ad4e", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.16, para 7](https://elifesciences.org/articles/95135)"}, "hash": "9048a3975a08e9ea8c0ac26eaf141eaa74b7ae69ff660a045301cef1d75eb561", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Users can simulate NeuroML models using a number of simulation engines without making any changes to their models. This is because the NeuroML/LEMS descriptions of the models are simulator independent and can be translated to simulator specific formats. pyNeuroML facilitates access to all available simulation options, both from the command line and using function calls in Python scripts when using the Python API (*Figure 6*).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 429, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f9917e11-49f6-46b2-a7f5-74cd5b6db9db": {"__data__": {"id_": "f9917e11-49f6-46b2-a7f5-74cd5b6db9db", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.16, para 8](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d6881dcf-cdaa-4bf9-b81a-c3a0f3c4f304", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.16, para 8](https://elifesciences.org/articles/95135)"}, "hash": "c8e0689e27a9dacfbc6ba5309c78559e4beb8ac5d06572c8af5f04f043a8ab95", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Simulation engines can be classified into five broad categories (*Figure 5*):", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 77, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "686d82fb-7750-4ae8-8bd5-1d0a70bc8414": {"__data__": {"id_": "686d82fb-7750-4ae8-8bd5-1d0a70bc8414", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.16, para 9](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8b6cb474-e9ea-465e-bf4a-e79318b11d1d", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.16, para 9](https://elifesciences.org/articles/95135)"}, "hash": "09a3e14ad9de43804702712688653c088eb49c91eede1de27fb3854678c72a73", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "1. reference NeuroML/LEMS simulators.\n2. independently developed simulators that natively support NeuroML.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 106, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "987fa3db-1908-4bab-9f11-1d6ecaf7f71c": {"__data__": {"id_": "987fa3db-1908-4bab-9f11-1d6ecaf7f71c", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.16, para 10](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "71ec380d-a6a4-4dfc-9d2c-16354e092d42", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.16, para 10](https://elifesciences.org/articles/95135)"}, "hash": "d92f8048cd96d65cbc8093e7af86415758e7b700152a0cb76d2d826f62e8e1ef", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135 16 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 94, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4c3b2bd4-e35e-42ca-8310-a95560ba249d": {"__data__": {"id_": "4c3b2bd4-e35e-42ca-8310-a95560ba249d", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.17, para 1](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d2698f31-6f90-4dd4-acf9-b27f4b0e65c9", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.17, para 1](https://elifesciences.org/articles/95135)"}, "hash": "23f40686978801937dda32b5d3f28d5fb91be31d0f31c62d06afbb9207d42294", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Table 6.** Listing of validation tests run by NeuroML.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 56, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ba0bfb5e-5092-4f74-8779-87fe83fe08f6": {"__data__": {"id_": "ba0bfb5e-5092-4f74-8779-87fe83fe08f6", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.17, para 2](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d7d89a89-e3c7-4554-aa16-b3ad8d091c39", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.17, para 2](https://elifesciences.org/articles/95135)"}, "hash": "2115a7f6e36c9de7b1707908798f3f9af501151d6fc5d7e61fc5be067e083097", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Test|Description|\n|-|-|\n|Schema tests||\n|Check names|Check that names of all elements, attributes, parameters match those provided in the schema|\n|Check types|Check that the types of all included elements|\n|Check values|Check that values follow given restrictions|\n|Check inclusion|Check that required elements are included|\n|Check cardinality|Check the number of elements|\n|Check hierarchy|Check that child/children elements are included in the correct parent elements|\n|Check sequence order|Check that child/children elements are included in the correct order|\n|Additional tests||\n|Check top level ids|Check that top level (root) elements have unique ids|\n|Check Network level ids|Check that child/children of the Network element have unique ids|\n|Check Cell Segment ids|Check that all Segments in a Cell have unique ids|\n|Check single Segment without parent|Check that only one Segment is without parents (the soma Segment)|\n|Check SegmentGroup ids|Check that all SegmentGroups in a Cell have unique ids|\n|Check Member segment ids exist|Check that Segments referred to in SegmentGroup Members exist|\n|Check SegmentGroup definition|Check that SegmentGroups being referenced are defined|\n|Check SegmentGroup definition order|Check that SegmentGroups are defined before being referenced|\n|Check included SegmentGroups|Check that SegmentGroups referenced by Include elements of other SegmentGroups exist|\n|Check numberInternalDivisions|Check that SegmentGroups define numberInternalDivisions (used by simulators to discretize un-branched branches into compartments for simulation)|\n|Check included model files|Check that model files included by other files exist|\n|Check Population component|Check that a component id provided to a Population exists|\n|Check ion channel exists|Check that an ion channel used to define a ChannelDensity element exists|\n|Check concentration model species|Check that the species used in ConcentrationModel elements are defined|\n|Check Population size|Check that the size attribute of a PopulationList matches the number of defined Instances|\n|Check Projection component|Check that Populations used in the Projection elements exist|\n|Check Connection Segment|Check that the Segment used in Connection elements exist|\n|Check Connection pre/post cells|Check that the pre- and post-synaptic cells used in Connection elements exist and are correctly specified|\n|Check Synapse|Check that the Synapse component used in a Projection element exists|\n|Check root id|Check that the root Segment in a Cell morphology has id 0|", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2544, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "454d20e6-2bfc-4c2f-adc4-e09f354669c2": {"__data__": {"id_": "454d20e6-2bfc-4c2f-adc4-e09f354669c2", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.17, para 3](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5a87b82b-0c03-446f-9fa7-f13d0ca31ff6", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.17, para 3](https://elifesciences.org/articles/95135)"}, "hash": "5c702974c54138e67090118af3e8983229fbe470c20f3f3ae0ffe030286f4675", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "3. simulators that import/translate NeuroML to their own internal formats.\n4. simulators that are supported through generation of simulator-specific scripts by the core NeuroML tools.\n5. export to other standardized formats which may allow simulation/analysis in other packages.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 278, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e44e582a-1248-4b07-a2e4-5339b16d9119": {"__data__": {"id_": "e44e582a-1248-4b07-a2e4-5339b16d9119", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.17, para 4](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0e5a75f6-be5e-4b04-9170-cb74e69af6c1", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.17, para 4](https://elifesciences.org/articles/95135)"}, "hash": "e14ee7f7e9a03fa6f441005a0d6de24ed846fe8158bda013a3c9408bfb9be551", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Each simulation engine supports a different set of features that NeuroML users can take advantage of (*Table 7*). For example, the reference NeuroML and LEMS simulators, jNeuroML, jLEMS, and PyLEMS, can simulate all LEMS models and most NeuroML models. They cannot, however, simulate", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 283, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f2306e67-cb69-4c86-afe5-978e4897a765": {"__data__": {"id_": "f2306e67-cb69-4c86-afe5-978e4897a765", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.17, para 5](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5266e446-9f70-4b13-8d0e-f815525c96a6", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.17, para 5](https://elifesciences.org/articles/95135)"}, "hash": "058400b9f88e60e4abed15f97b841d3fb77d5ad7d8497214adcb60f1f280fb0c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135 17 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 94, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "342392fa-fd5c-4e99-8dd7-bdaf4bc346d3": {"__data__": {"id_": "342392fa-fd5c-4e99-8dd7-bdaf4bc346d3", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.18, para 1](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b9bc399d-19b1-42f7-aee1-76c5c59cd585", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.18, para 1](https://elifesciences.org/articles/95135)"}, "hash": "30ad4b9864f6e35625e5694d210041a6bd465730136ed1266c128b11c0678d1b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**a.**\nThe image shows an interactive 3-D visualization of an olfactory bulb network with detailed mitral and granule cells, featuring a complex web of colorful neuronal morphologies (blue, green, red, and purple lines) interconnected in a spherical arrangement.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 262, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3cc34cd4-20c5-4426-9769-00e81e9e8ec1": {"__data__": {"id_": "3cc34cd4-20c5-4426-9769-00e81e9e8ec1", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.18, para 3](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5370a342-0751-451d-aaf8-b3bdd66226c3", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.18, para 3](https://elifesciences.org/articles/95135)"}, "hash": "20c4a549049126052a3296bedabfc742f4e606b932fca935c562ea559947347e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|OPEN SOURCE BRAIN|search projects|Q|My Projects \u25be|Explore OSB|Help|Admin|sanjay\\_ankur \u25be|\n|-|-|-|-|-|-|-|-|\n|MultiscaleISN|\u27f2 Return to project \\[Troubleshoot 3D explorer]|||||||\n|Connectivity Model Description Results \u2699 Run \u25b6 Play \u23f8 Pause \u25fc Stop \ud83d\udec8 Help||||||||", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 261, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6c8f3075-4752-463a-90a4-4169de6ff0fa": {"__data__": {"id_": "6c8f3075-4752-463a-90a4-4169de6ff0fa", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.18, para 4](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "10bf9307-992c-4656-a266-4ef6e462455e", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.18, para 4](https://elifesciences.org/articles/95135)"}, "hash": "72c768208b45db1a156f29f940671959490b30abbf69dea298d33e9f35264b3f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The image displays a 3D visualization within the Open Source Brain (OSB) version 1 interface, showing an inhibition stabilized network with numerous red and blue spherical nodes representing neurons and green branching structures representing their dendritic/axonal processes.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 276, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "571dc309-37c5-438d-b363-ac8116a55d67": {"__data__": {"id_": "571dc309-37c5-438d-b363-ac8116a55d67", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.18, para 6](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "157f7736-d953-4548-b69d-2abfc1d1238f", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.18, para 6](https://elifesciences.org/articles/95135)"}, "hash": "8f7df1281820ac5609234ea1de32b1038630bdd41d51b55a3fb4d9cac5f85c93", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Open Source Brain v2.0|padraig|padraig|padraig|padraig|padraig|padraig|padraig|\n|-|-|-|-|-|-|-|-|\n|+ NetPyNE|File|View|Model|Examples|Help|BACK TO EDIT|SIMULATE \u25be|", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 164, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5b5c1833-9f0f-4ea4-9c9c-051cf154d7c0": {"__data__": {"id_": "5b5c1833-9f0f-4ea4-9c9c-051cf154d7c0", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.18, para 7](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9cc91be5-6bb9-4498-bdac-79d088f47a43", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.18, para 7](https://elifesciences.org/articles/95135)"}, "hash": "c90348e289cc4fa573b23322efe0ba387c3fe32e3a8daf1d2c94a0dcb9e8a52f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The image shows the NetPyNE GUI embedded in OSB version 2. It includes:", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 71, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2ed28a9e-3f2c-4314-9ac7-6f6157253b59": {"__data__": {"id_": "2ed28a9e-3f2c-4314-9ac7-6f6157253b59", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.18, para 8](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3d44b9f1-4aee-4930-b0ab-debeef28637b", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.18, para 8](https://elifesciences.org/articles/95135)"}, "hash": "a0f002ab0afeb26b2539d8ea16413bf0b84ae6e788644e1edd292075bd0b5be7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* A **3D Representation** panel showing white branching neuronal morphologies with highlighted segments in orange and green.\n* A **Rate Spectrogram Plot** panel showing multiple heatmaps of activity over time (0-200 ms) for different cell populations (allCells, CG3D\\_L23Pyr, etc.).\n* A **Raster plot** panel showing spiking activity (dots) for different cells (ordered by gid) over time (0-200 ms).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 399, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "224dd4d5-c193-488f-b2c0-6d20064306ea": {"__data__": {"id_": "224dd4d5-c193-488f-b2c0-6d20064306ea", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.18, para 9](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5f988cd6-4983-430c-8265-3f0cad45b4f4", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.18, para 9](https://elifesciences.org/articles/95135)"}, "hash": "978d71549974f8f1f1972b929fb086e7984f53b23ad6165edab58620606acb9c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Figure 8.** Visualization of detailed neuronal morphology of neurons and networks together with their functional properties (results from model simulation) enabled by NeuroML. (**a**) Interactive 3-D (VisPy (**Campagnola, 2023**) based) visualization of an olfactory bulb network with detailed mitral and granule cells (**Migliore et al., 2014**), generated using pyNeuroML. (**b**) Visualization of an inhibition stabilized network based on **Sadeh et al., 2017** using Open Source Brain (OSB) version 1 (**Gleeson et al., 2019b**). (**c**) Visualization of 3D network of simplified multi-compartmental cortical neurons (from **Traub et al., 2005**, imported as NeuroML **Gleeson, 2019a**) and simulated spiking activity using NetPyNE\u2019s GUI (**Dura-Bernal et al., 2019**), which is embedded in OSB version 2.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 811, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "bffd93cb-4ac5-4f18-81ab-8e53ad527ff5": {"__data__": {"id_": "bffd93cb-4ac5-4f18-81ab-8e53ad527ff5", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.18, para 10](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "755b2bac-8823-4075-bfd0-b4ba6af3f8fb", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.18, para 10](https://elifesciences.org/articles/95135)"}, "hash": "ea8adc41782a818455d08c9f94805cc7b9bd17c5044c60367ea94d5d529d1b33", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135\n18 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 94, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9b2325c0-457f-448e-8943-302ed18e4511": {"__data__": {"id_": "9b2325c0-457f-448e-8943-302ed18e4511", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.19, para 2](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ef83c81a-8337-43ae-b084-4b804e96799e", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.19, para 2](https://elifesciences.org/articles/95135)"}, "hash": "a26d2cf7fe633c11332af0ebc719bc014108c83ccb4652a0238ab005f04f8e1a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|presynaptic \\ postsynaptic|HL23PV\\_pop|HL23PYR\\_pop|HL23SST\\_pop|HL23VIP\\_pop|\n|-|-|-|-|-|\n|HL23PV\\_pop|10000|10000|10000|10000|\n|HL23PYR\\_pop|20000|70000|25000|10000|\n|HL23SST\\_pop|10000|30000|10000|10000|\n|HL23VIP\\_pop|10000|0|30000|10000|", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 242, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f96d4880-a2ff-4884-a9bf-8ae9bd358b6e": {"__data__": {"id_": "f96d4880-a2ff-4884-a9bf-8ae9bd358b6e", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.19, para 3](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "64231c23-d62e-4e19-b7d4-d6175f202766", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.19, para 3](https://elifesciences.org/articles/95135)"}, "hash": "941caed60ccfbfb09629be860dfb300c134cad2cf46a25dced1f3b66e0d7cb4b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "*Note: Values are estimated from the color scale provided in the figure (0 to 70000).*", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 86, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6914606b-2244-4490-a560-066b1d1c1389": {"__data__": {"id_": "6914606b-2244-4490-a560-066b1d1c1389", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.19, para 4](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ae9cfad4-3a2c-4c85-8caa-1984837342e5", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.19, para 4](https://elifesciences.org/articles/95135)"}, "hash": "3d331945b1530bd4761beea9da0df01892e8993e9eca4bc81287ba4b5dedaab5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Figure 9.** Analysis and visualization of network connectivity from NeuroML model descriptions *prior to simulation*. Network connectivity schematic (**a**) and connectivity matrix (**b**) for a half scale implementation of the human layer 2/3 cortical network model (**Yao et al., 2022**) generated using pyNeuroML.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 318, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "589ac71a-fd18-4ea5-82ef-3b3cda5c1f36": {"__data__": {"id_": "589ac71a-fd18-4ea5-82ef-3b3cda5c1f36", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.19, para 5](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "61fec5be-a589-4462-8b18-474bdad40f1b", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.19, para 5](https://elifesciences.org/articles/95135)"}, "hash": "de352b7ebb5356ef4db396c36e3f02ef10ab1327191b7429b0b237b519fa5db4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "multi-compartmental models, and users should opt for a simulator that does, e.g., NEURON (**Hines and Carnevale, 1997**) or EDEN (**Panagiotou et al., 2022**).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 159, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "92eb1455-b7cf-49bf-a543-62f0c059a571": {"__data__": {"id_": "92eb1455-b7cf-49bf-a543-62f0c059a571", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.19, para 6](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "90a5923c-3ab2-400b-9e19-f6a78c1a2d16", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.19, para 6](https://elifesciences.org/articles/95135)"}, "hash": "3f2a4a0f1c8aefd3dcb93c462d6e0abc04f7fe45895f3af27e70bf6200008f46", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Another criteria that is relevant when choosing a simulation engine is the efficiency of simulation. Simulation engines implement different computing techniques\u2014e.g., NetPyNE, Arbor, and EDEN support parallel execution on clusters and super computers via MPI\u2014to enable simulation of large-scale models. Thus, for efficient large-scale simulation, users may prefer one of these simulation engines.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 396, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "21ac019b-2177-4137-a83b-a5368fa18805": {"__data__": {"id_": "21ac019b-2177-4137-a83b-a5368fa18805", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.19, para 7](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e4e5a7a0-fcef-4674-82fa-ab66c1f5467a", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.19, para 7](https://elifesciences.org/articles/95135)"}, "hash": "4ef8116a05ed3c0b99ef20872238bb2b34c4ff027671e55c9b461158784ad9a7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The preferred programming language for working with NeuroML is Python (**Muller et al., 2015**). A Python-based ecosystem ensures that automated simulation of models can easily be carried out either using scripts, or the command line tools. Utilities to enable the execution of simulations on dedicated supercomputing resources, such as the Neuroscience Gateway (NSG) (**Sivagnanam, 2013**;", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 390, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4f2e6b9b-d359-47a0-99fe-e7ce0e23aaa1": {"__data__": {"id_": "4f2e6b9b-d359-47a0-99fe-e7ce0e23aaa1", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.19, para 8](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "987e96ba-b0ea-4e02-990b-18c4ddbd4998", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.19, para 8](https://elifesciences.org/articles/95135)"}, "hash": "51565b6b08cc60053cff2b8a5a07a489762c143b324e1ab1d9d2d9fa434b0aa0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Table 7.** Features supported by NeuroML in different simulation engines.\nNote: the simulators themselves may support more features, but these have not been mapped onto by the NeuroML tools. Abstract cell models: abstract cell models included in the NeuroML standard (see ***Table 1***). Single compartmental cells: neuronal models that include a single compartment (these engines do not support multi-compartmental cells). Multiple compartmental cells: neuronal models that include multiple compartments. Conductance-based models: models that support ionic conductances. Parallel execution: engines that support parallel execution using MPI/GPUs. Y: full support; N: no support; L: limited support in NeuroML toolchain.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 722, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "254dec49-e427-4abe-84e0-bc6ab6e6f997": {"__data__": {"id_": "254dec49-e427-4abe-84e0-bc6ab6e6f997", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.19, para 9](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7d3d9b5d-a3f4-43d2-b5d4-757808b1f842", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.19, para 9](https://elifesciences.org/articles/95135)"}, "hash": "e5b5b55706a206c659b84154f7c787fc204175f1eb151d5ab9e881dbfea76899", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Tool|Abstract cell models|Single compartment cells|Multiple compartment cells|Conductance-based models|Parallel execution|\n|-|-|-|-|-|-|\n|jNeuroML/pyNeuroML|Y|Y|N|Y|N|\n|NEURON|Y|Y|Y|Y|N|\n|NetPyNE|Y|Y|Y|Y|Y|\n|EDEN|Y|Y|Y|Y|Y|\n|MOOSE|Y|Y|L|Y|N|\n|PyNN|Y|Y|L|L|Y|\n|NEST|Y|Y|N|N|Y|\n|Brian2|Y|Y|Y|Y|L|\n|Arbor|L|Y|Y|L|Y|", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 313, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "237b2bd9-2952-425a-a14e-96556bfd3a6e": {"__data__": {"id_": "237b2bd9-2952-425a-a14e-96556bfd3a6e", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.19, para 10](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5774d740-05f9-460d-b017-5126b20b6ed9", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.19, para 10](https://elifesciences.org/articles/95135)"}, "hash": "1de0d87dd4c9feda9e928e463ded34d63b887a2ab259909f329bc147fe9924ea", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135 19 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 94, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4b9de0f0-db78-4954-bf7b-d36cbf07a553": {"__data__": {"id_": "4b9de0f0-db78-4954-bf7b-d36cbf07a553", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.20, para 2](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bc525276-85f3-47fb-8bb9-2c61e075dc07", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.20, para 2](https://elifesciences.org/articles/95135)"}, "hash": "64fe80b868d39ffb52e735f191a5201c64b5e1d8900c20ba2a341ee616a3a5f2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "\\[!NOTE]\n**NeuroML-DB Interface**\nSearch | Gallery | API | Documentation | About | NeuroML Home", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 95, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1fbed21f-74e3-400d-a98a-8ee4207d1cfc": {"__data__": {"id_": "1fbed21f-74e3-400d-a98a-8ee4207d1cfc", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.20, para 3](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e6c357f4-c9cc-4960-a046-6a57a07bc945", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.20, para 3](https://elifesciences.org/articles/95135)"}, "hash": "3877aac045cd83f890f29d53113613fa4d642f8bb3d8a0fc990b394437866dc8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Layer 5b Pyramidal cell**\n\\[ Overview ] \\[ Electrophysiology ] \\[ Morphology ] \\[ Computational Complexity ]", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 110, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4e5c80a1-5d7f-4131-b808-e7cbeb5d907c": {"__data__": {"id_": "4e5c80a1-5d7f-4131-b808-e7cbeb5d907c", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.20, para 4](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2f981b07-4bf5-4c74-a571-b237e1222309", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.20, para 4](https://elifesciences.org/articles/95135)"}, "hash": "8e95608a535c4a04d3958d23c2d3c17dfceff57adff4d4ffd455000927d66bbb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Current Clamp Response**\nProtocol: \\[ Square (Long) ] Stimulus: **ALL**", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 73, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c4734f16-9ed0-4618-b055-7ebf8bcdc521": {"__data__": {"id_": "c4734f16-9ed0-4618-b055-7ebf8bcdc521", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.20, para 6](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "93dbaa64-2270-40e6-becd-c29e90504b92", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.20, para 6](https://elifesciences.org/articles/95135)"}, "hash": "70fb5bda462229aaf97d26a43edf5bb543f515995430955430995da4dfd5a856", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "| Time (ms)   | Voltage (mV) (approx. range)         |\n| :---------- | :----------------------------------- |\n| 0 - 1000    | -80                                  |\n| 1000 - 3000 | Spiking activity between -80 and +40 |\n| 3000 - 3250 | -80                                  |", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 274, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "55b8cd2a-1ced-4fef-b612-0bc993cde817": {"__data__": {"id_": "55b8cd2a-1ced-4fef-b612-0bc993cde817", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.20, para 8](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c05f2b86-f51c-4f5a-8f70-be7d122caab8", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.20, para 8](https://elifesciences.org/articles/95135)"}, "hash": "f4846718ab320bc7625fbd1321f088013b2976088b8411e04f506514fc66b549", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "| Time (ms)   | Current (nA) (approx. levels)          |\n| :---------- | :------------------------------------- |\n| 0 - 1000    | 0.0                                    |\n| 1000 - 3000 | Four steps: \\~0.4, \\~0.6, \\~0.8, \\~1.0 |\n| 3000 - 3250 | 0.0                                    |", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 284, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "95aed62d-d90f-4e8b-a234-5e01be946d0b": {"__data__": {"id_": "95aed62d-d90f-4e8b-a234-5e01be946d0b", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.20, para 10](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "273464d0-75b2-4565-a763-9130ca988b14", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.20, para 10](https://elifesciences.org/articles/95135)"}, "hash": "88331ca4c602347cc8e7277b810749ba838366c6192f4f81b4f47b29840304de", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Membrane potential (mV)|Steady state - inf (na\\_channel m inf)|Steady state - inf (na\\_channel h inf)|\n|-|-|-|\n|-100|0.0|1.0|\n|-50|0.2|0.2|\n|0|0.9|0.0|\n|50|1.0|0.0|\n|100|1.0|0.0|", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 179, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1e0be431-aced-4558-85dd-1f3afada30d0": {"__data__": {"id_": "1e0be431-aced-4558-85dd-1f3afada30d0", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.20, para 11](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "608cf4af-e707-49be-a14a-3fadfe3c7ec8", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.20, para 11](https://elifesciences.org/articles/95135)"}, "hash": "605ddecf38d4c17a75628a83d8efc3e269ed3a3cf1fb38a5142c40ff08df8a18", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Membrane potential (mV)|Time Course - tau (ms) (na\\_channel m tau)|Time Course - tau (ms) (na\\_channel h tau)|\n|-|-|-|\n|-100|\\~0.1|\\~1.0|\n|-70|\\~0.2|\\~8.5|\n|-50|\\~0.4|\\~4.0|\n|0|\\~0.5|\\~1.0|\n|100|\\~0.5|\\~1.0|", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 208, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "247a7cae-d11f-4770-a085-fea0aee9ed34": {"__data__": {"id_": "247a7cae-d11f-4770-a085-fea0aee9ed34", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.20, para 12](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e8f22e19-8b09-4440-a3b4-91b92bcea1d7", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.20, para 12](https://elifesciences.org/articles/95135)"}, "hash": "874017cf00d5d4d4f7fbaee4dbfa672ecf25fd362eee07f46bde825d55ab5a6e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**c.**\n**Morphology and Conductance Distribution**\nThe image shows a visualization of a Layer 5 Pyramidal cell where the color of the neurites represents the peak conductance for the Ih channel (S/m^2).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 202, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "71306300-9c50-4c37-913b-7a69f3adcdb7": {"__data__": {"id_": "71306300-9c50-4c37-913b-7a69f3adcdb7", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.20, para 13](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8791c4c3-ea38-43b2-88b2-d0740981956f", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.20, para 13](https://elifesciences.org/articles/95135)"}, "hash": "71e82286d8fa5d9613deb9f3170f842439163d0bbc84c025b8540c49bc685f63", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* **x-axis:** x (\\mu m) ranging from -200 to 1200.\n* **y-axis:** y (\\mu m) ranging from -200 to 100.\n* **Color Scale (S/m^2):**\n  * Purple/Blue: \\~20\n  * Pink/Red: \\~60-80\n  * Orange/Yellow: \\~100-140 (primarily in the distal apical dendrites).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 244, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "54631315-dbd6-4f9d-974e-31c02388ce59": {"__data__": {"id_": "54631315-dbd6-4f9d-974e-31c02388ce59", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.20, para 14](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b7f168ac-d2c2-47bc-a8cf-a7925107246d", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.20, para 14](https://elifesciences.org/articles/95135)"}, "hash": "948992bd841e7cb8eca569eb0879db2214b296dc884605bd739cc9370b265f6b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Figure 10.** Examples of visualizing biophysical properties of a NeuroML model neuron. (**a**) Electrophysiological properties generated by the NeuroML-DB web-based platform (**Birgiolas et al., 2023**). (Plots show four superimposed voltage traces in the top panel and corresponding current injection traces below). (**b**) Example plots of steady states of activation (na\\_channel na\\_m inf) and inactivation (na\\_channel na\\_h inf) variables and their time courses (na\\_channel na\\_m tau and na\\_channel na\\_h tau) for the Na channel from the classic Hodgkin Huxley model (**Hodgkin and Huxley, 1952**). (**c**) The distribution of the peak conductances for the Ih channel over a layer 5 Pyramidal cell (**Hay et al., 2011**). Both (**b**) and (**c**) were generated using the analysis features in pyNeuroML, and similar functionality is also available in OSBv1 (**Gleeson et al., 2019b**).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 895, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c7ae79c6-f6cf-4622-aafa-07809b53b731": {"__data__": {"id_": "c7ae79c6-f6cf-4622-aafa-07809b53b731", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.20, para 15](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "64a47dd0-3a29-4dee-93a7-74518191df6c", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.20, para 15](https://elifesciences.org/articles/95135)"}, "hash": "ee1e1fa29fdbc5a9ed11d8854c3e147522b0a7b7e331874d74a868694ecdb84c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135 20 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 94, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0316b4f7-56d2-4676-8c21-bb6bd5a6ed03": {"__data__": {"id_": "0316b4f7-56d2-4676-8c21-bb6bd5a6ed03", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.21, para 1](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a7c0b7ee-61c4-4fe3-8eba-b88e86856271", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.21, para 1](https://elifesciences.org/articles/95135)"}, "hash": "e7e6e37fea463afefe0b73527114592c12951c6af2df23bf069c3fd6d1829b7d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ") are also available within the ecosystem. OSBv1 takes advantage of these to support the submission of NeuroML model simulation jobs using the NEURON simulator on NSG. NetPyNE also includes parallel execution of simulations, batch processing, and parameter exploration features, and its deployment on OSBv2 allows users to easily access these features on a scalable, cloud-based platform. Finally, the JupyterLab environment on OSBv2 contains all of the core NeuroML tools and various simulation engines as pre-installed software packages, ready to use.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 553, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "467e805f-2260-476d-9fae-7e00699419f5": {"__data__": {"id_": "467e805f-2260-476d-9fae-7e00699419f5", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.21, para 2](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f2bed865-bd95-4146-802e-ff20e1079aed", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.21, para 2](https://elifesciences.org/articles/95135)"}, "hash": "c582953d6c84a10d7b52e2a5774b46bd5163ff2975249c291203bec9c98ee40e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Optimizing NeuroML models", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 28, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d0d911b0-f98b-4c4f-8b2d-9258761e2c45": {"__data__": {"id_": "d0d911b0-f98b-4c4f-8b2d-9258761e2c45", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.21, para 3](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ac566e54-2bc1-4146-a977-d52ae47382d2", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.21, para 3](https://elifesciences.org/articles/95135)"}, "hash": "aef761616ea83c072cd322590bde8f894c0a7e3c8a1ff371035c9fb62eb5d851", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Development of biologically detailed models of brain function requires that components and emergent properties match the behavior of the corresponding biology as closely as possible. Thus, fitting neurons and networks to experimental data is a critical step in the model life cycle (*Rossant et al., 2011; Druckmann et al., 2007*). pyNeuroML promotes data-driven modeling by providing functions to fit and optimize NeuroML models against experimental data. It includes the NeuroMLTuner module (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 494, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0804dc77-d7bc-4cb9-a029-29e0216b17bc": {"__data__": {"id_": "0804dc77-d7bc-4cb9-a029-29e0216b17bc", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.21, para 5](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b8540423-98ff-4f23-ba40-aad7938faf59", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.21, para 5](https://elifesciences.org/articles/95135)"}, "hash": "d8b8afd2664dc6e14bf5e51b080b575967da090210579407470baf052b771dce", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "; *Vella and Gleeson, 2023*) for tuning and optimizing NeuroML models against data using evolutionary computation techniques. This module allows users to select a set of weighted features from their data to calculate the fitness of populations of candidate models. In each generation, the fittest models are found and mutated to create the next generation of models, until a set of models that best exhibit the selected data features are isolated (see Guide 6 in **Table 5**) (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 477, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1ec6c6d8-6b13-43c1-80e9-67c4eda65cb0": {"__data__": {"id_": "1ec6c6d8-6b13-43c1-80e9-67c4eda65cb0", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.21, para 6](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0376f63d-9465-4f5e-9e9e-fba30c39fd83", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.21, para 6](https://elifesciences.org/articles/95135)"}, "hash": "9f66e5dbd21bc104167575386436937bc6dfd48e4dea887979cd4033ab1f88d4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ").", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "242dee92-9bfb-478b-a741-bdc5d05b135b": {"__data__": {"id_": "242dee92-9bfb-478b-a741-bdc5d05b135b", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.21, para 7](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c7799267-a19f-4dde-96b7-dd541db0dc51", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.21, para 7](https://elifesciences.org/articles/95135)"}, "hash": "fb33f907315132c54eba3089aaf95d68bd5803322b63780b2a71314ec199c08e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The NeuroML ecosystem includes multiple tools that also provide model fitting features. The Blue Brain Python Optimisation Library (BluePyOpt) (*Van Geit et al., 2016*), an extensible framework for data-driven model parameter optimization, supports exporting optimized models to NeuroML files (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 294, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7630c87b-2cb8-4eaf-b1e8-df26e185a3e5": {"__data__": {"id_": "7630c87b-2cb8-4eaf-b1e8-df26e185a3e5", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.21, para 8](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ff585e8c-f4a2-49c0-95cb-888738b1f3ba", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.21, para 8](https://elifesciences.org/articles/95135)"}, "hash": "62a193f90339bca8bb712d86615c2922ef56ab46d72ff465a4c05c2a79fd3e0e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "). Similar to pyNeuroML, NetPyNE also uses the inspyred Python package (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 72, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "702b3489-5dfd-4e70-a69a-75e919a78831": {"__data__": {"id_": "702b3489-5dfd-4e70-a69a-75e919a78831", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.21, para 9](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2b08493e-95e2-47a2-a33f-1193bd6d764b", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.21, para 9](https://elifesciences.org/articles/95135)"}, "hash": "45dc083e552ce730adbafef0e567e3dca1c39444f3dcec8f14153d5adfcc3e19", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "; *Sinha and Garrett, 2024*) to provide evolutionary computation-based model optimization features (*Dura-Bernal et al., 2019*).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 128, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "dbf2b63a-72d7-4d37-af06-798d11ce9099": {"__data__": {"id_": "dbf2b63a-72d7-4d37-af06-798d11ce9099", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.21, para 10](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "92baf479-cf3a-491f-8c1a-f6a3b3ba6f37", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.21, para 10](https://elifesciences.org/articles/95135)"}, "hash": "0f7b6b8f44e71d0000d99a0d7f41e636119065b26c396f020e206d87c59cca0f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Sharing NeuroML models", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 25, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0c2c56c7-11e8-40a4-92b6-40ece95a01d5": {"__data__": {"id_": "0c2c56c7-11e8-40a4-92b6-40ece95a01d5", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.21, para 11](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "235b9082-19d6-43c5-8fa3-cf2af027619a", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.21, para 11](https://elifesciences.org/articles/95135)"}, "hash": "c4c3c521018d0384a6f540b1e84399ee8b470df79faec8a0b350c3bf809eb50b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The NeuroML ecosystem includes the advanced web-based model sharing platforms NeuroML-DB (*Birgiolas et al., 2023*;", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 115, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ec5cafcb-348f-44be-8d90-b09c9f6b3bcd": {"__data__": {"id_": "ec5cafcb-348f-44be-8d90-b09c9f6b3bcd", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.21, para 12](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a7d5a0c7-a28d-4aa8-87de-b7da68196847", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.21, para 12](https://elifesciences.org/articles/95135)"}, "hash": "296c3e5bfbf67b57e79874f4859be41127fd82925e0b2314c7bed2849cb2835a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ") and OSB (*Gleeson et al., 2019b*). These resources have been designed specifically for the dissemination of models and model elements standardized in NeuroML. The OSB platform also supports visualization, analysis, simulation, and development of NeuroML models. Researchers can create shared, collaborative NeuroML projects on it and can take advantage of the in-built automated visualization and analysis pipelines to explore and re-use models and their components. Whereas version 1 (OSBv1) focused on providing an interactive 3D interface for running pre-existing NeuroML models (e.g. sourced from linked GitHub repositories) (*Gleeson et al., 2019b*), OSBv2 provides cloud-based workspaces for researchers to construct NeuroML-based computational models as well as analyze, and compare them to, the experimental data on which they are based, thus facilitating data-driven computational modeling. **Table 8** provides a list of stable, well-tested NeuroML compliant models from brain regions including the neocortex, cerebellum, and hippocampus, which have been shared on OSB.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1081, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a31668d2-78ff-4930-8cc1-9d45ae545f82": {"__data__": {"id_": "a31668d2-78ff-4930-8cc1-9d45ae545f82", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.21, para 13](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "638d46be-2b8c-4bc1-adb1-e7932f237f4a", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.21, para 13](https://elifesciences.org/articles/95135)"}, "hash": "fa2078985dd51805e1e09162dc2a56268aec0cce0f37d3de24ae089e308a78a0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "NeuroML-DB aims to promote the uptake of standardized NeuroML models by providing a convenient location for archiving and exploration. It includes advanced database search functions, including ontology-based search (*Birgiolas et al., 2015*), coupled with pre-computed analyses on models\u2019 electrophysiological and morphological properties, as well as an indication of the relative speed of execution of different models.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 420, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "de27a267-8a44-44de-89fa-a2bd3ab63b04": {"__data__": {"id_": "de27a267-8a44-44de-89fa-a2bd3ab63b04", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.21, para 14](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2bcb6660-48c5-4a17-a051-eb48001ec39e", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.21, para 14](https://elifesciences.org/articles/95135)"}, "hash": "b35479e136bb64b5eff91ff4d6830e3aafd9476f30cc1b7079c8c53a8c6a0263", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "NeuroML\u2019s modular nature ensures that models and their components can be easily shared with others through standard code sharing resources. The simplest way of sharing NeuroML models and components is to make their Python descriptions or their XML serializations available through these resources. Indeed, it is straightforward to make Python descriptions or the XML serializations available via different file, code (GitHub, GitLab), model sharing (ModelDB *Migliore et al., 2003; McDougal et al., 2017*), and archival (Zenodo, Open Science Framework) platforms, just like any other code/data produced in scientific investigations. Complex models with many components, spanning multiple files,", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 694, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3952cb7d-66e3-412f-a189-d0503734865d": {"__data__": {"id_": "3952cb7d-66e3-412f-a189-d0503734865d", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.21, para 15](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "53234a99-2188-4a6f-8804-724a5f6b7b49", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.21, para 15](https://elifesciences.org/articles/95135)"}, "hash": "786e96fedb20c5e60eca58993655c5481aa7e08d91e3c4d5bf78b26a4df1cb7f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: [https://doi.org/10.7554/eLife.95135](https://doi.org/10.7554/eLife.95135) 21 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 133, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e3b20f7b-4779-4d94-964c-65e888f7b11a": {"__data__": {"id_": "e3b20f7b-4779-4d94-964c-65e888f7b11a", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.22, para 1](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1918a297-a8d3-47aa-8033-4c7123e37889", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.22, para 1](https://elifesciences.org/articles/95135)"}, "hash": "5527e12f071bbe402ce41194f5381937328a5b85409313bb7a120f5dde1bfc8c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Table 8.** Listing of NeuroML models and example repositories.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 64, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0b9e4dd0-fe92-4893-9010-b1949497ca02": {"__data__": {"id_": "0b9e4dd0-fe92-4893-9010-b1949497ca02", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.22, para 2](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ac3466c5-9ca5-4c86-a5fe-bf4f0129c28e", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.22, para 2](https://elifesciences.org/articles/95135)"}, "hash": "39df2c31cb7f71b4775c326712a43d04ec0fcd53d7e0fbe355d018fe212605ba", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Model|Description|URL|\n|-|-|-|\n|Neocortex|||\n|Billeh et al., 2020|Morphologically detailed and point neuron models based on electrophysiological recordings from visual cortex neurons|https://github.com/OpenSourceBrain/AllenInstituteNeuroML|\n|Brunel, 2000|Spiking network illustrating balance between excitation and inhibition|https://github.com/OpenSourceBrain/Brunel2000|\n|Hay et al., 2011|Layer 5 pyramidal cell model constrained by somatic and dendritic recordings|https://github.com/OpenSourceBrain/L5bPyrCellHayEtAl2011|\n|Izhikevich, 2004|Spiking neuron model reproducing wide range of neuronal activity|https://github.com/OpenSourceBrain/IzhikevichModel|\n|Markram et al., 2015|Cell models from Neocortical Microcircuit of Blue Brain Project|https://github.com/OpenSourceBrain/BlueBrainProjectShowcase|\n|Pospischil et al., 2008|HH-based models for different classes of cortical and thalamic neurons|https://github.com/OpenSourceBrain/PospischilEtAl2008|\n|Potjans and Diesmann, 2014|Microcircuit model of sensory cortex with 8 populations across 4 layers|https://github.com/OpenSourceBrain/PotjansDiesmann2014|\n|Dura-Bernal et al., 2017|Model of mouse primary motor cortex (M1)|https://github.com/OpenSourceBrain/M1NetworkModel|\n|Sadeh et al., 2017|Point neuron model of Inhibition Stabilized Network|https://github.com/OpenSourceBrain/SadehEtAl2017-InhibitionStabilizedNetworks|\n|Smith et al., 2013|Layer 2/3 cell model used to investigate dendritic spikes|https://github.com/OpenSourceBrain/SmithEtAl2013-L23DendriticSpikes|\n|Traub et al., 2005|Single column network model containing 14 cell populations from cortex and thalamus|https://github.com/OpenSourceBrain/Thalamocortical|\n|Bahl et al., 2012|A set of reduced models of layer 5 pyramidal neurons|https://github.com/OpenSourceBrain/BahlEtAl2012\\_ReducedL5PyrCell|\n|Wilson and Cowan, 1972|A classic rate-based model describing the dynamics and interactions between the excitatory and inhibitory populations of neurons|https://github.com/OpenSourceBrain/WilsonCowan|\n|Garcia Del Molino et al., 2017|Rate-based model showing paradoxical response reversal of top-down modulation in cortical circuits with three interneuron types|https://github.com/OpenSourceBrain/del-Molino2017|\n|Mejias et al., 2016|A rate-based model simulating the dynamics of a cortical laminar structure across multiple scales: intralaminar, interlaminar, interareal and whole cortex|https://github.com/OpenSourceBrain/MejiasEtAl2016|\n|Cerebellum|||\n|Maex and Schutter, 1998|Cerebellar granule cell|https://github.com/OpenSourceBrain/GranuleCell|\n|Cayco-Gajic et al., 2017|Cerebellar granule cell layer network|https://github.com/SilverLabUCL/MF-GC-network-backprop-public|\n|Maex and Schutter, 1998|3D Cerebellar granule cell layer network|https://github.com/OpenSourceBrain/GranCellLayer|\n|Solinas et al., 2007|Cerebellar Golgi cell model|https://github.com/OpenSourceBrain/SolinasEtAl-GolgiCell|\n|Vervaeke et al., 2010|Electrically connected cerebellar Golgi cell network model|https://github.com/OpenSourceBrain/VervaekeEtAl-GolgiCellNetwork|\n|Hippocampus|||\n|Bezaire et al., 2016|Full scale network model of CA1 region of hippocampus|https://github.com/mbezaire/ca1|", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 3201, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "865ba36f-3ea5-4b21-9fa5-a335c46ec986": {"__data__": {"id_": "865ba36f-3ea5-4b21-9fa5-a335c46ec986", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.22, para 4](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "44127778-27b0-4f45-927f-0bf6cc8727f1", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.22, para 4](https://elifesciences.org/articles/95135)"}, "hash": "b4e0c60408031a52f0826244a3665afc8f0a1577fc052ffb115272abcc0fab17", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135 22 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 94, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e8072156-46a1-46a5-a0b0-1701dae859fa": {"__data__": {"id_": "e8072156-46a1-46a5-a0b0-1701dae859fa", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.23, para 2](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fff07399-b5b7-4198-84ba-37340514ad76", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.23, para 2](https://elifesciences.org/articles/95135)"}, "hash": "a2f2f088e88b30f0d7dcc15a62d28a8bdcc8bc0d488e6dbb5094abb5f00c406f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Model|Description|URL|\n|-|-|-|\n|Ferguson et al., 2013|Parvalbumin-positive interneuron from CA1, based on Izhikevich cell model|https://github.com/OpenSourceBrain/FergusonEtAl2013-PVFastFiringCell|\n|Ferguson et al., 2014|Pyramidal cell from CA1, based on Izhikevich cell model|https://github.com/OpenSourceBrain/FergusonEtAl2014-CA1PyrCell|\n|Migliore et al., 2005|Multi-compartmental model of pyramidal cell from CA1 region of hippocampus|https://github.com/OpenSourceBrain/CA1PyramidalCell|\n|Pinsky and Rinzel, 1994|Simplified model of CA3 pyramidal cell|https://github.com/OpenSourceBrain/PinskyRinzelModel|\n|Wang and Buzs\u00e1ki, 1996|Hippocampal interneuronal network model exhibiting gamma oscillations|https://github.com/OpenSourceBrain/WangBuzsaki1996|\n|Olfactory bulb|||\n|Migliore et al., 2014|Large-scale 3D olfactory bulb network with detailed mitral cells and granule cells|https://github.com/OpenSourceBrain/MiglioreEtAl14\\_OlfactoryBulb3D|\n|Invertebrate|||\n|Hodgkin and Huxley, 1952|Classic investigation of the ionic basis of the action potential|https://github.com/openworm/hodgkin\\_huxley\\_tutorial|\n|FitzHugh, 1961|Simplified form of Hodgkin Huxley model|https://github.com/OpenSourceBrain/FitzHugh-Nagumo|\n|Prinz et al., 2004|Pyloric network of the lobster stomatogastric ganglion system|https://github.com/OpenSourceBrain/PyloricNetwork|\n|Boyle and Cohen, 2008|Model of body wall muscle from C. elegans|https://github.com/openworm/muscle\\_model|\n|Gleeson et al., 2018|A multiscale framework for modeling the nervous system of C. elegans|https://github.com/openworm/c302|\n|General|||\n|Morris and Lecar, 1981|Two dimensional reduced neuron model with calcium and potassium conductances|https://github.com/OpenSourceBrain/MorrisLecarModel|\n|Hindmarsh and Rose, 1984|A simplified point cell model which captures complex firing patterns of single neurons, such as periodic and chaotic bursting|https://github.com/OpenSourceBrain/HindmarshRose1984|\n|Showcases|||\n|NEST Showcase|Examples of interactions with simulator NEST|https://github.com/OpenSourceBrain/NESTShowcase|\n|PyNN Showcase|Examples of interactions between NeuroML and PyNN|https://github.com/OpenSourceBrain/PyNNShowcase|\n|NetPyNE Showcase|Examples of interactions between NeuroML and NetPyNE|https://github.com/OpenSourceBrain/NetPyNEShowcase|\n|SBML Showcase|Examples of interactions between NeuroML and SBML|https://github.com/OpenSourceBrain/SBMLShowcase|\n|Brian Showcase|Examples of interactions between NeuroML and Brian|https://github.com/OpenSourceBrain/BrianShowcase|\n|MOOSE Showcase|Examples of interactions between NeuroML and MOOSE|https://github.com/OpenSourceBrain/MOOSEShowcase|\n|Arbor Showcase|Examples of interactions between NeuroML and Arbor|https://github.com/OpenSourceBrain/ArborShowcase|\n|EDEN Showcase|Examples of interactions between NeuroML and EDEN|https://github.com/OpenSourceBrain/EDENShowcase|\n|The Virtual Brain Showcase|Examples of interactions between NeuroML and TVB|https://github.com/OpenSourceBrain/TheVirtualBrainShowcase|", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 3034, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8b718159-6d01-4145-839c-735d8ff943e4": {"__data__": {"id_": "8b718159-6d01-4145-839c-735d8ff943e4", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.23, para 4](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c6ea231a-1227-45d9-b53e-a19e3656faaf", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.23, para 4](https://elifesciences.org/articles/95135)"}, "hash": "53bf2fb4d192ff22dc359005c28f5677e5979ebd8b84e63e38f8f597b085f4b0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135 23 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 94, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "76ad78f9-6d84-4019-8e06-7bc1411fc863": {"__data__": {"id_": "76ad78f9-6d84-4019-8e06-7bc1411fc863", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.24, para 2](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ea9797a5-d9c8-4f6d-9cee-964e05bc1ef7", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.24, para 2](https://elifesciences.org/articles/95135)"}, "hash": "ec8913a737eb6afae57ba4f21c5e1e30cfa8e42b9308ec6b8193ea263fdb0c90", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Model|Description|URL|\n|-|-|-|\n|NEURON Showcase|Examples of interactions between NeuroML and NEURON|https://github.com/OpenSourceBrain/NEURONShowcase|\n|neuroConstruct Showcase|Examples of neuroConstruct projects|https://github.com/OpenSourceBrain/neuroConstructShowcase|\n|NeuroMorpho.Org|Examples of reconstructions from NeuroMorpho.Org|https://github.com/OpenSourceBrain/NeuroMorpho|\n|Janelia MouseLight|Janelia MouseLight project neuronal reconstructions|https://github.com/OpenSourceBrain/MouseLightShowcase|", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 512, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "bcd9d267-ce6b-4340-99f0-27d1aedb88ae": {"__data__": {"id_": "bcd9d267-ce6b-4340-99f0-27d1aedb88ae", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.24, para 3](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0fa3586c-fd6d-49d8-8bee-b0975ecedca7", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.24, para 3](https://elifesciences.org/articles/95135)"}, "hash": "70d2a2a1b67f05412774b0fb2c8007a2185c48e8ec43205fb532c409f093b67d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "such as networks and neuronal models that reference multiple cell and ionic conductance definitions, can also be exported into a COMBINE zip archive (*Bergmann et al., 2014*), a zip file that includes metadata about its contents. pyNeuroML includes functions to easily create COMBINE archives from NeuroML models and simulations (*Figure 6*).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 342, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e7e33eaf-71fb-427b-8f7c-dc3eb3196222": {"__data__": {"id_": "e7e33eaf-71fb-427b-8f7c-dc3eb3196222", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.24, para 4](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "58938a00-3a24-487e-a12b-8ed721902369", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.24, para 4](https://elifesciences.org/articles/95135)"}, "hash": "18c8e6ae7f17f8d8a428f782dccf4f6139d81028faaf33411dec0f1e1bed8700", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "OSB is designed so that researchers can share their code on their chosen platform (e.g. GitHub), while retaining full control over write access to their repositories. Afterwards, a page for the model can be created on OSB which lists the latest files present there, with links to OSB visualization/analysis/simulation features which can use the standardized files found in the resource.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 386, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fb1ed945-e8be-4530-8ae6-272af178e87a": {"__data__": {"id_": "fb1ed945-e8be-4530-8ae6-272af178e87a", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.24, para 5](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b7b520bf-412d-4106-9072-c3818552da75", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.24, para 5](https://elifesciences.org/articles/95135)"}, "hash": "d98c0c79e99c129eaa079e62390d2582265625fedecc15d4e0874fbdd1c10934", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "NeuroML supports the embedding of structured ontological information in model descriptions (*Neal et al., 2019*). Models can include NeuroLex (now InterLex) (*Larson and Martone, 2013*) identifiers for their components (e.g. neuro\\_lex\\_id in *Figure 6*). This links model components to their biological counterparts and makes them more transparent, findable, and reusable. For example, different types of neurons and brain regions have unique ontological ids. A user can use these ids to search for relevant model components on NeuroML-DB. More general information to maintain provenance can also be included in NeuroML models (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 629, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ade7fbf9-6e16-4f7f-b712-5690221e34f5": {"__data__": {"id_": "ade7fbf9-6e16-4f7f-b712-5690221e34f5", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.24, para 6](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2d739f0e-e60d-48b5-81a9-6aa5954d6d6e", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.24, para 6](https://elifesciences.org/articles/95135)"}, "hash": "797988d671d14cf62a2d3beb94e9dbe4aff887c7bbffc898ceaacad30866b010", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ").", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6e069473-1c52-4720-b4cc-0df9c6e6ffe1": {"__data__": {"id_": "6e069473-1c52-4720-b4cc-0df9c6e6ffe1", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.24, para 7](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0177f648-b6de-40eb-b591-833e0dceac87", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.24, para 7](https://elifesciences.org/articles/95135)"}, "hash": "24eb0f35483ed1fffdf5b16cb24110ce70c2b93a445df55bc0e2f3cf512be0b8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Reusing NeuroML models", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 25, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "355f73ca-622e-4264-92cf-b243e77857f8": {"__data__": {"id_": "355f73ca-622e-4264-92cf-b243e77857f8", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.24, para 8](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ed272ac0-a55f-4405-9a17-605344e81f7a", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.24, para 8](https://elifesciences.org/articles/95135)"}, "hash": "2902fdf696159d4f7dec6020a11b429f0725823f6c41d7037b511150fc5fc29e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "NeuroML models, once openly shared, become community resources that are accessible to all. Researchers can use models shared on NeuroML-DB and OSB without restrictions. Guide 5 in *Table 5* provides an example of finding NeuroML-based model components using the API of NeuroML-DB, and creating novel models incorporating these elements.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 336, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c2e7f9cc-21f1-4994-afc6-6527427e7c3d": {"__data__": {"id_": "c2e7f9cc-21f1-4994-afc6-6527427e7c3d", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.24, para 9](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "025c15d6-8459-4e2c-b0e5-c2548fa2cc65", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.24, para 9](https://elifesciences.org/articles/95135)"}, "hash": "a0708753b4bb65f2ee6c853d42168a6c96614e966d72914f9f0e1a7e22d702e4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In addition to these platforms, other experimental data and model dissemination platforms also provide standardized NeuroML versions of relevant models to promote uptake and reuse. For example, NeuroMorpho.org (*Ascoli et al., 2007*) includes a tool to download NeuroML compliant versions of its cellular reconstructions (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 322, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7fa076e9-fae3-4d20-a484-5239f4ed163c": {"__data__": {"id_": "7fa076e9-fae3-4d20-a484-5239f4ed163c", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.24, para 10](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8d67188a-ce61-4aa0-819f-2f31cff7e0f4", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.24, para 10](https://elifesciences.org/articles/95135)"}, "hash": "bca73075df7db1c3e3af05c751436a1cbaa73cdced606c906afc54d315cad4ab", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ",", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b1b9d44b-3867-4527-b908-8cec7dd8b54a": {"__data__": {"id_": "b1b9d44b-3867-4527-b908-8cec7dd8b54a", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.24, para 11](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8ba9d88b-e19a-40dd-a963-c1cadd0eb803", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.24, para 11](https://elifesciences.org/articles/95135)"}, "hash": "6565ec216033035d6708f773269a1afcb6f45f0380ccb05a1d37ee4a26ba6a0a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "). NeuroML versions of models released by organizations such as the Blue Brain Project (*Markram et al., 2015*) (whole cell models as well as ion channel models from Channelpedia *Ranjan et al., 2011*), the Allen Institute for Brain Science (*Billeh et al., 2020*), and the OpenWorm project (*Gleeson et al., 2018*) are also openly available for reuse (*Table 8*).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 364, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2bd23b6c-bbab-49d1-a54c-8f003a2a3e2f": {"__data__": {"id_": "2bd23b6c-bbab-49d1-a54c-8f003a2a3e2f", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.24, para 12](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "364bd76f-8558-4bc0-9108-43574a8b57c0", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.24, para 12](https://elifesciences.org/articles/95135)"}, "hash": "ba7673d9ec92c1cb2a1aa6c2d58a885a88cf8364e715072068e5e30fda33e8c7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "NeuroML can also interact with other standards to further promote model re-use. Whereas NeuroML is a declarative standard, PyNN (*Davison et al., 2008*) is a procedural standard with a Python API for creating network models that can be simulated on multiple simulators. NeuroML models which are within the scope of PyNN can be converted to the PyNN format, and vice-versa. Similarly, NeuroML also interacts with SONATA (*Dai et al., 2020*) data format by supporting the two way conversion of the network structures of NeuroML models into SONATA. In standards not specific to neuroscience, models from the well established SBML standard (*Hucka et al., 2003*) can be converted to LEMS (*Cannon et al., 2014*), for inclusion in neuroscience-related modeling pipelines, and a subset of NeuroML/LEMS models can be exported to SBML, which allows use with simulators and analysis packages compliant to this standard, e.g., Tellurium (*Choi et al., 2018*). Simulation execution details of NeuroML/LEMS models can also be exported to Simulation Experiment Description Markup Language (SED-ML) (*Waltemath et al., 2011*), allowing advanced resources such as Biosimulators (*Shaikh et al., 2022*) (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1188, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "265cdfb4-78d0-4311-89ce-1463adcd40f0": {"__data__": {"id_": "265cdfb4-78d0-4311-89ce-1463adcd40f0", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.24, para 13](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "954239f4-c8d2-4bce-8f3b-b14297175e69", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.24, para 13](https://elifesciences.org/articles/95135)"}, "hash": "256d6fe000531c17bc7b641a5baffac1b321ffb33847db561d504dbd56a92ece", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ") to feature NeuroML models.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 28, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "480faa99-5ad8-4ff0-b020-62d73ef2655c": {"__data__": {"id_": "480faa99-5ad8-4ff0-b020-62d73ef2655c", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.24, para 14](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a628312b-ede0-46b0-9e79-c16a2cfc1092", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.24, para 14](https://elifesciences.org/articles/95135)"}, "hash": "206d9a1edeadb16cec2131387301b2fac74be96ebc9f9e18a582b71ccbfeeec6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135 24 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 94, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c4aecc9d-6aae-4fce-adbe-cd08375a3809": {"__data__": {"id_": "c4aecc9d-6aae-4fce-adbe-cd08375a3809", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.25, para 1](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1e91dfea-f56d-4f11-bf6f-ef37594d119d", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.25, para 1](https://elifesciences.org/articles/95135)"}, "hash": "887335c7cf8d03c388b3834974387bcc9aa7e37c1d02fd4dd352768411aca2bc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## NeuroML is extensible", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 24, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3ba645b8-b468-451b-a48e-417d95cc5dee": {"__data__": {"id_": "3ba645b8-b468-451b-a48e-417d95cc5dee", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.25, para 2](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cad693ff-5748-43ff-b9bc-c056e7da2023", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.25, para 2](https://elifesciences.org/articles/95135)"}, "hash": "f80f91aa2932636fce50cbc4de18c64815174ba1ffb826caa51e00991bd0c214", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "While the standard NeuroML elements (*Tables 1 and 2*) provide a broad range of curated model types for simulation-based investigations, NeuroML can be extended (using LEMS) to incorporate novel model elements and types when they are not (yet) available in the standard.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 270, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e0181b2e-3267-43a6-80b1-551d0b84c551": {"__data__": {"id_": "e0181b2e-3267-43a6-80b1-551d0b84c551", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.25, para 3](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "000cc89f-4f24-480c-ac73-bce7d2900fb3", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.25, para 3](https://elifesciences.org/articles/95135)"}, "hash": "1b923a0b35022e716e5a0853364846bc881aeb0f811172fc04a88003881cb693", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "LEMS is a general purpose model specification language for creating fully machine readable definitions of the structure and behavior of model elements (*Cannon et al., 2014*). The dynamics of NeuroML elements are described in LEMS. The hierarchical nature of LEMS means that new elements can build on pre-existing elements of the modular NeuroML framework. For example, a novel ionic conductance element can extend the \u2018ionChannelHH\u2019 element, which in turn extends \u2018baseIonChannel.\u2019 Thus, the new element will be known to the NeuroML elements as depending on an external voltage and producing a conductance, properties that are inherited from \u2018baseIonChannel.\u2019 Other elements, such as a cell, can incorporate this new type without needing any other information about its internal workings.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 789, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "dc07bb8c-6a1d-41d5-940c-cddca5c3e17d": {"__data__": {"id_": "dc07bb8c-6a1d-41d5-940c-cddca5c3e17d", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.25, para 4](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7f299c9f-d43c-4339-ba0f-11f8cdc64038", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.25, para 4](https://elifesciences.org/articles/95135)"}, "hash": "2d3122ab7933cd917d55666759a29b93c6515d91c47f224b396ec444fa5a61f3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "LEMS (and, therefore, NeuroML) element definitions (called \u2018ComponentTypes\u2019) specify the dynamical behavior of the model element in terms of a list of yet to be set parameters. Once the generic model behavior is defined, modelers only need to fill in the appropriate values of the required parameters (e.g. conductance density, reversal potential, etc.) to create new instances (called \u2018Components\u2019) of the element (see Methods for more details). Users can, therefore create arbitrary, reusable model elements in LEMS, which can be treated the same way as the standard model elements (for an example see Guide 7 in *Table 5*).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 626, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c4cadeea-0df8-4c65-b8bd-769ea557ed36": {"__data__": {"id_": "c4cadeea-0df8-4c65-b8bd-769ea557ed36", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.25, para 5](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "78f149b5-9cc9-4510-bf38-c0cfc2a112f2", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.25, para 5](https://elifesciences.org/articles/95135)"}, "hash": "eb8e3f273eeae99917ad2e0fcc71fa37b30857b1831b53f777650c1009c86ae7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Another major advantage of NeuroML\u2019s use of the LEMS language is its translatability. Since LEMS is fully machine readable, its primitives (e.g. state variables and their dynamics, expressed as ordinary differential equations) can be readily mapped into other languages. As a result, simulator specific code (*Blundell et al., 2018*) can be generated from NeuroML models and their LEMS extensions (*Figure 5*), allowing NeuroML to remain simulator-independent while supporting multiple simulation engines.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 505, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "eae781db-34f5-4870-8cfc-de5baef5ae74": {"__data__": {"id_": "eae781db-34f5-4870-8cfc-de5baef5ae74", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.25, para 6](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c793230d-8f67-4418-921a-5f5ea7a7fa7c", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.25, para 6](https://elifesciences.org/articles/95135)"}, "hash": "dde7037abc0af84ab2a53f648e2b20cb0c9412cf1681b73597cb8edeb1e0cfd9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Newly created elements that may be of interest to the wider research community can be submitted to the NeuroML Editorial Board for inclusion into the standard. The standard, therefore, evolves as new model elements are added and improved versions of the standard and associated software tool chain are regularly released to the community.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 338, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "18b1b786-bcb4-4baf-9a63-877e16c79519": {"__data__": {"id_": "18b1b786-bcb4-4baf-9a63-877e16c79519", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.25, para 7](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "029d83a1-631d-4e52-897c-851b94092c80", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.25, para 7](https://elifesciences.org/articles/95135)"}, "hash": "d0e21e1fe386e6ef9524bf5637478ca79e9ed1320ef7a14e6efbc11a35dc5eb5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## NeuroML is a global open community initiative", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 48, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e1581933-1e95-46ad-a3f9-d9f8cc137e5a": {"__data__": {"id_": "e1581933-1e95-46ad-a3f9-d9f8cc137e5a", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.25, para 8](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fbe198a8-8edd-4e98-aa3f-1051e9f906b3", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.25, para 8](https://elifesciences.org/articles/95135)"}, "hash": "48e2fe211a56e63bdcbde117289e9ff074b8ffafa8f24bd9973cafaff1d84806", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "NeuroML is a global open community standard that is used and maintained collectively by a diverse set of stakeholders. The NeuroML Scientific Committee (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 153, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7bf84622-0d1e-41da-bc67-a21b293aa8dc": {"__data__": {"id_": "7bf84622-0d1e-41da-bc67-a21b293aa8dc", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.25, para 10](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0194699d-4200-4a2c-bb16-aaa6e320dafa", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.25, para 10](https://elifesciences.org/articles/95135)"}, "hash": "b9299077033fed5db7d39f268f59001ec8e719b38dde890791a0a0d850e130f8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ") oversee the standard, the core tools, and the initiative. This ensures that NeuroML supports the myriad of use cases generated by a multi-disciplinary computational modeling community.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 186, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a64f9279-1bd3-41b0-b0e3-808a6fb8c742": {"__data__": {"id_": "a64f9279-1bd3-41b0-b0e3-808a6fb8c742", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.25, para 11](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "368ae5ba-626e-4125-86bb-d1d6dc1d1623", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.25, para 11](https://elifesciences.org/articles/95135)"}, "hash": "49f8e9f9d6e2155fa7fb817102eac1c40ebb2e481b700993740b8fffdead9853", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "NeuroML is an endorsed INCF (*Abrams et al., 2022*) community standard (*Martone and Das, 2019*) and is one of the main standards of the international COMBINE initiative (*Hucka et al., 2015*), which supports the development of other standards in computational biology as well (e.g. SBML (*Hucka et al., 2003*) and CellML *Lloyd et al., 2004*). Participation in these organizations guarantees that NeuroML follows current best practices in standardization, and remains linked to and interoperable with other standards wherever possible. The NeuroML community also participates in training and outreach activities such as Google Summer of Code (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 644, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fbb87247-cece-4f04-8fa9-31fe71c849ea": {"__data__": {"id_": "fbb87247-cece-4f04-8fa9-31fe71c849ea", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.25, para 12](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "44c4fb95-c646-4509-ac7f-927ea3995cc0", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.25, para 12](https://elifesciences.org/articles/95135)"}, "hash": "841dc87dc94876ad054d849839b4bbf3e534f3785cdd1505502a0df894e17c7f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "), tutorials, and internships under these and other organizations.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 66, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3227a4df-5423-4e9c-b0f4-383ff77c1cdb": {"__data__": {"id_": "3227a4df-5423-4e9c-b0f4-383ff77c1cdb", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.25, para 13](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ecbf0331-f6bc-4a78-a772-a3157050c324", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.25, para 13](https://elifesciences.org/articles/95135)"}, "hash": "7c70345db00e0cc2ea7dc5d169e1f99e388e71409d0828fa94fd5e00ec5f07b3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The NeuroML community maintains public open communication channels to ensure that all community members can easily participate in troubleshooting, discussions, and development activities. A public mailing list (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 211, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "bb8b7076-49e9-4088-8e87-8108ea405c6e": {"__data__": {"id_": "bb8b7076-49e9-4088-8e87-8108ea405c6e", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.25, para 14](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5dec224f-14da-4a7e-9604-a34b6810ea03", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.25, para 14](https://elifesciences.org/articles/95135)"}, "hash": "eb00d9a8ef619945e5d540c14ede92baebd8f9f3d8721a2be094d1bc531460ac", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ") is used for asynchronous communication and announcements while open chat channels on Gitter (now Matrix/Element (#/#NeuroML\\_community:gitter.im)) provide immediate access to the NeuroML community. All software repositories hosted on GitHub also have issue trackers for software specific queries. A community Code of Conduct (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 328, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e6463bb9-17c5-4086-a777-aa16b8e9150c": {"__data__": {"id_": "e6463bb9-17c5-4086-a777-aa16b8e9150c", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.25, para 15](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4bb4f7f3-236a-479e-897a-56e2d4dfa5cc", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.25, para 15](https://elifesciences.org/articles/95135)"}, "hash": "d08901f8dd61281a93acc18b4f1e714f3f8728f0e7c7727e24350abb4cf526f1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ") sets the standards of communication and behavior expected on all community channels.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 86, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "79c0505d-f988-493b-bb27-4708a7bb250f": {"__data__": {"id_": "79c0505d-f988-493b-bb27-4708a7bb250f", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.25, para 16](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5c574a17-e239-4395-a532-55cc8d8f0909", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.25, para 16](https://elifesciences.org/articles/95135)"}, "hash": "9db72849b7ad39dce8f881df3a36148fb809410845f1e3acc813b6a63f6124d1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135 25 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 94, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "831bbb17-a763-4d64-a7f9-723094908694": {"__data__": {"id_": "831bbb17-a763-4d64-a7f9-723094908694", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.26, para 1](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f6183dbf-85e3-4ce4-9506-313937d8bbd5", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.26, para 1](https://elifesciences.org/articles/95135)"}, "hash": "f01c1bf7c59ebfa49b47d9b475465f25965eb4eb63a2bb2035ed2811f23ab783", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "A crucial aim of NeuroML is to enable Open Science and ensure models in computational neuroscience are FAIR. To this end, all development and discussions related to NeuroML are done publicly. The schema, all core software tools, and relevant resources such as documentation are made freely available under suitable Free/Open Source Software (FOSS) licenses on public platforms. Everyone can, therefore, use, modify, study, and share all NeuroML artifacts without restriction. Users and developers are encouraged to contribute modifications and improvements to the schema and core tools and to participate in the general maintenance and release process.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 652, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8146c221-9808-498b-979c-e5404b8a02b1": {"__data__": {"id_": "8146c221-9808-498b-979c-e5404b8a02b1", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.26, para 2](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "556c235d-ca07-4808-9c60-fd2848201d3b", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.26, para 2](https://elifesciences.org/articles/95135)"}, "hash": "84bd3408b47f88d4088366324d747b2752304349d4a0b87e5906edbf58d327b2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Discussion", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 12, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "02efa0c7-09ca-4cc2-8298-c2b7b7f0b517": {"__data__": {"id_": "02efa0c7-09ca-4cc2-8298-c2b7b7f0b517", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.26, para 3](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cbde376a-b296-4865-a9e2-63fb7227fd74", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.26, para 3](https://elifesciences.org/articles/95135)"}, "hash": "e9f92ceb973a814fb5b731efaedbf6cd3a62ab4b9abbaf7ee0abdefbc06cd802", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "NeuroMLv2 has matured into a widely adopted community standard for computational neuroscience. Its modular, hierarchical structure can define a wide range of neuronal and circuit model types including simplified representations and those with a high degree of biological detail. The standardized, machine readable format of the NeuroMLv2/LEMS framework provides a flexible, common language for communicating between a wide range of tools and simulators used to create, validate, visualize, analyze, simulate, share, and reuse models. By enabling this interoperability, NeuroMLv2 has spawned a large ecosystem of interacting tools that cover all stages of the model development life cycle, bringing greater coherence to a previously fragmented landscape. Moreover, the modular nature of the model components and hierarchical structure conferred by NeuroMLv2, combined with the flexibility of coding in Python, has created a powerful \u2018building block\u2019 approach for constructing standardized models from scratch.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1008, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "35a79150-b0f5-4115-9d6a-a8db991acf42": {"__data__": {"id_": "35a79150-b0f5-4115-9d6a-a8db991acf42", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.26, para 4](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "411434ef-1e36-47ed-87e8-4470f374ca48", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.26, para 4](https://elifesciences.org/articles/95135)"}, "hash": "584444f5a9c39bb805ababd5bfcc1aa1425718a8700c0da7244675b86b337d46", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "NeuroML has, therefore, evolved from a standardized archiving format into a mature language that supports an ecosystem of tools for the creation and execution of models that support the FAIR principles and promote open, transparent, and reproducible science.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 258, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1d12cd1c-21c2-4fe7-82e6-c70af6bb02eb": {"__data__": {"id_": "1d12cd1c-21c2-4fe7-82e6-c70af6bb02eb", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.26, para 5](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "63dfb82e-b556-4648-8b8d-982c2a2b6cb6", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.26, para 5](https://elifesciences.org/articles/95135)"}, "hash": "98a51b7d5e75d27221dff43cd2b606aa0a2f7faa2cc1210b2017df644cd291c3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Evolution of NeuroML and emergence of the NeuroMLv2 tool ecosystem", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 69, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "30571eef-fa9f-4e28-b24b-fc9741edbc0c": {"__data__": {"id_": "30571eef-fa9f-4e28-b24b-fc9741edbc0c", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.26, para 6](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7915ab61-80ed-4eae-a728-fe0d91cbb42c", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.26, para 6](https://elifesciences.org/articles/95135)"}, "hash": "256bb27a528bdae472010ff21cbb35f513b6723a254c4db7e90ed88fe65cd680", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "NeuroML was conceived (*Goddard et al., 2001*) and developed (*Gleeson et al., 2010*) as a declarative XML-based framework for defining biophysical models of neurons and networks in a standardized form in order to compare model properties across simulators and to promote transparency and reuse. NeuroML version 1 achieved these aims and was mainly used to archive and visualize existing models (*Gleeson et al., 2010*). Building on this, the subsequent development of the NeuroMLv2/LEMS framework provided a way to describe models as a hierarchical set of components with dimensional parameters and state variables, so that their structure and dynamics are fully machine readable (*Cannon et al., 2014*). This enabled models to be losslessly mapped to other representations, greatly promoting interoperability between tools through read-write and automated code generation (*Blundell et al., 2018*). As NeuroMLv2 matured and became a community standard recognized by the INCF with a formal governance structure, an increasingly wide range of models and modeling tools have been developed or modified to be NeuroMLv2 compliant (*Tables 8, 3 and 4*). The core tools, maintained directly by the NeuroML developers (*Figure 4*), provide functionality to read, modify, or create new NeuroML models, as well as to analyze and visualize, and simulate the models. Furthermore, there are now a larger number of tools that have been developed by other members of the community (*Figure 3*) including a neuronal simulator designed specifically for NeuroMLv2 (*Panagiotou et al., 2022*). The emergence of an ecosystem of NeuroMLv2 compliant tools enables modelers to build tool chains that span the model life cycle and build and reuse standardized models.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1745, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6b2eed1b-9ca9-40db-946d-28733ea7b6bc": {"__data__": {"id_": "6b2eed1b-9ca9-40db-946d-28733ea7b6bc", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.26, para 7](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6f90b4e5-2bb9-4075-b6a6-c13da081660e", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.26, para 7](https://elifesciences.org/articles/95135)"}, "hash": "948bed081bb8eb41b517cae48374520d5072dc84de420c84690d5573d8423775", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## NeuroML and other standards in computational neuroscience", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 60, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "507b44e8-a96f-40e5-9941-b028b6396952": {"__data__": {"id_": "507b44e8-a96f-40e5-9941-b028b6396952", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.26, para 8](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3cc5b4c9-8257-4cc2-a7a0-2e1fa919f9b9", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.26, para 8](https://elifesciences.org/articles/95135)"}, "hash": "cac84bffba8455987d041d8423a2b6202f61940939ffcd568dd65717e5a6fa07", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Several other standards and formats exist to support computational modeling of neuronal systems. Whereas NeuroML is a modular, declarative simulator independent standard for biophysical neuronal modeling, PyNN (*Davison et al., 2008*) and SONATA (*Dai et al., 2020*) provide a procedural Python-based simulator independent API and a framework for efficiently handling large-scale network simulations, respectively. Even though there is some overlap in the functionality provided by these standards, they each target distinct use cases and have their own goals and features. The teams developing these standards work in concert to ensure that they remain interoperable with each other, frequently sharing methods and techniques (*Dai et al., 2020*). This allows researchers to use their standard of choice and", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 808, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e9530e1c-c26c-410e-a51f-df76a5d04ed6": {"__data__": {"id_": "e9530e1c-c26c-410e-a51f-df76a5d04ed6", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.26, para 9](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "05b621aa-5494-4c53-8e45-24d9ff37901d", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.26, para 9](https://elifesciences.org/articles/95135)"}, "hash": "54f5d985e05e4bc250bc2bcb599f9e7697437567ff64aa74cf8f1d28b9561bc3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135 26 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 94, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "586bb720-53d0-4e23-8243-5f953edd49dd": {"__data__": {"id_": "586bb720-53d0-4e23-8243-5f953edd49dd", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.27, para 1](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "da38211b-4505-4550-83d0-be976af91f45", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.27, para 1](https://elifesciences.org/articles/95135)"}, "hash": "ffd1218df19b0b4cd5e4829a041ec1c8ee4b36f96b0c6d23a27418bc899de2f0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "easily combine with another if the need arises. PyNN and SONATA are, therefore, integral parts of the wider NeuroML ecosystem.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 126, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "dc8b2aa4-73a3-464e-98d2-ddb2285e5f6f": {"__data__": {"id_": "dc8b2aa4-73a3-464e-98d2-ddb2285e5f6f", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.27, para 2](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b4466be1-c6af-4d75-af5d-faf5310e3739", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.27, para 2](https://elifesciences.org/articles/95135)"}, "hash": "ef7c5e1bf37cf41038856b5361c7817cd96f76445976146624bca127680d3fae", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Why using NeuroML and Python promotes the construction of FAIR models", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 72, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3964526d-575c-432a-aea5-13e99e0f297d": {"__data__": {"id_": "3964526d-575c-432a-aea5-13e99e0f297d", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.27, para 3](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "dc5573bb-35b4-4cf3-b28f-dc4e0d5ae6ec", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.27, para 3](https://elifesciences.org/articles/95135)"}, "hash": "a8164339f39a5ad5c29fb28ef661ae130286df574b733998e10132045dea42b2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The modular and hierarchical structure of NeuroMLv2, when combined with Python, provides a powerful combination of structured declarative elements and flexible procedural approaches that enables a \u2018Lego-like\u2019 building block approach for constructing biologically detailed models (*Cayco-Gajic et al., 2017; Billings et al., 2014; Kriener et al., 2022; Gurnani and Silver, 2021*). This has been advanced by the development of pyNeuroML, which provides a single installable package offering direct access to a range of functionality for handling NeuroML models (*Figure 6*). Moreover, the web-based documentation of NeuroMLv2, with multiple Python scripts illustrating the usage of the language and associated tools (*Table 5*), has recently been updated and expanded (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 767, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "74f23007-2c4c-4349-b712-dee31b1e0da7": {"__data__": {"id_": "74f23007-2c4c-4349-b712-dee31b1e0da7", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.27, para 4](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "38b6d3d1-9832-4bf3-85de-d5fc22ae9688", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.27, para 4](https://elifesciences.org/articles/95135)"}, "hash": "4977eff04b879498f450c7b488a45e2bb2c1946f1fab8366e410e789cd45186e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "). This provides a central resource for both new and experienced users of NeuroML supporting its use in model building. As the examples of this resource illustrate, building models using NeuroMLv2 is efficient and intuitive, as the model components are pre-made and how they fit together specified. The structured format allows APIs like libNeuroML to incorporate features such as auto-completion and inline validation of model parameters and structure as scripts are being developed. In addition, automated multi-stage model validation ensures the code, equations and internal structure are validated against the NeuroML schema minimizing human errors and model simulations outputs are within acceptable bounds (*Figure 7*). The NeuroMLv2 ecosystem also provides convenient ways to visualize and inspect the inner structure of models. pyNeuroML provides Python functions and corresponding command line utilities to view neuronal morphology (*Figure 8*), neuronal electrophysiology (*Figure 10*), circuit connectivity and schematics (*Figure 9*). In addition, custom analysis pipelines and advanced neuroinformatics resources can easily be built using the APIs. For example, loading a NeuroML model of a neuron into OSB enables visualization of the morphology and the spatial distribution of ionic conductance over the membrane as well as inspection of the conductance state variables, while the connectivity and synaptic weight matrices can be automatically displayed for circuit models (*Figure 8; Gleeson et al., 2019b*). Such features of OSB, which are made possible by the structured format of NeuroMLv2, promote model transparency, reproducibility, and sharing. By enabling the development and sharing of well tested and transparent models the wider NeuroMLv2 ecosystem promotes Open Science.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1798, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7d27fbe8-313d-46c1-a199-4e4044b5a313": {"__data__": {"id_": "7d27fbe8-313d-46c1-a199-4e4044b5a313", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.27, para 5](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e1125c20-0243-416e-9cf6-0253ff974b8d", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.27, para 5](https://elifesciences.org/articles/95135)"}, "hash": "8e2ece73622bba2a176ef7bdc5912f304645c32a67b49311fe2b9a0f5c08ede3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Limitations of NeuroML and current work", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 42, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "af418c4a-1811-4cc2-aee7-ebcc280c1c56": {"__data__": {"id_": "af418c4a-1811-4cc2-aee7-ebcc280c1c56", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.27, para 6](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "884cfc09-2d6a-440e-91a4-9d84883cf61a", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.27, para 6](https://elifesciences.org/articles/95135)"}, "hash": "caf486371b46d9371d23ef69c6ebde60796759d53ba6bed8d55ffd64b37c924f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "A limitation of any standardized framework is that there will always be models and model elements that fall outside the current scope of the standard. Although NeuroML suffers from this limitation, the underlying LEMS-based framework provides a flexible route to develop a wide range of new types of physio-chemical models (*Cannon et al., 2014*). This is relatively straightforward if the new model component, such as a synaptic plasticity mechanism, fits within the existing hierarchical structure of NeuroMLv2 as the new type of synaptic element can build on an existing base synapse type which specifies the relevant input and outputs (e.g. local voltage and synaptic current). For more radical shifts in model types (e.g. neuronal morphologies that grow during learning) that do not fit neatly into the current NeuroMLv2 schema, structural changes to the language would be required. This route is more involved as the pros and cons of changes to the structure of NeuroMLv2 would need to be considered by the Scientific Committee and, if approved, implemented by the Editorial Board.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1087, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "414d9031-593c-4a40-95ea-13a3d9d331ec": {"__data__": {"id_": "414d9031-593c-4a40-95ea-13a3d9d331ec", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.27, para 7](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a79471bb-3775-4657-90aa-2520a41c98fe", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.27, para 7](https://elifesciences.org/articles/95135)"}, "hash": "0103d37bd6bc5b44b859cc851014ec2d6afc8add31fed4e8240d55f9cef19855", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Whereas the current scope of NeuroMLv2 encompasses models of spiking neurons and networks at different levels of biological detail, plans are in place to extend its scope to include more abstract, rate-based models of neuronal populations (e.g. see *Wilson and Cowan, 1972; Mejias et al., 2016 in Table 8*). Additionally, work is under way to extend current support for SBML (*Hucka et al., 2003*) based descriptions of chemical signaling pathways (*Cannon et al., 2014*), to enable better biochemical descriptions of sub-cellular activity in neurons and synapses.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 564, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9b42afa5-282d-4ff3-8fd8-5c15e4f276ab": {"__data__": {"id_": "9b42afa5-282d-4ff3-8fd8-5c15e4f276ab", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.27, para 8](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "884bfa6f-a61a-4363-b28f-e2508c193ad1", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.27, para 8](https://elifesciences.org/articles/95135)"}, "hash": "d30879baeae590c08ceddfbe5d1d965b4f62a326ebf47db248c9b245b5aa2086", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "There is a growing interest in the field for the efficient generation and serialization of large-scale network models, containing numbers of neurons closer to their biological equivalents (*Markram et al., 2015; Billeh et al., 2020; Einevoll et al., 2019*). While a multitude of applications in the NeuroML ecosystem support large-scale model generation (e.g. NetPyNE, neuroConstruct, PyNN), the default", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 403, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "bdc01cf0-e05c-40b9-9f5f-cc130c3453e6": {"__data__": {"id_": "bdc01cf0-e05c-40b9-9f5f-cc130c3453e6", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.27, para 9](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b335e652-f08e-46a0-a202-84c9cb6eec1f", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.27, para 9](https://elifesciences.org/articles/95135)"}, "hash": "442d233b0a43ff6150fdb3b2f5f50fc27b6eceba5fb4ad2d4a9de490052d3641", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135 27 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 94, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cc48d805-1a8d-4377-89e6-e26fd1f291de": {"__data__": {"id_": "cc48d805-1a8d-4377-89e6-e26fd1f291de", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.28, para 1](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4c009a05-de8a-4716-a9d7-08a45635c4c7", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.28, para 1](https://elifesciences.org/articles/95135)"}, "hash": "742d8bd18acd9b0691b83dbf809e5ed0c298d4cca46aeefc89d3d3ac9956f0f9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "serialization of NeuroML (XML) is inefficient for reading/writing/storing such extensive descriptions. NeuroML does have an internal format for serializing in the binary format HDF5 (see Methods), but has also recently added support for export of models to the SONATA data format (Dai et al., 2020) allowing efficient serialization of large-scale models. Even though individual instances of large-scale models are useful, the ability to generate families of these for multiple simulation runs and more particularly a way to encapsulate, examine and reuse templates for network models, is also required. A prototype package, NeuroMLlite (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 637, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9f499df6-d150-4089-bd1e-dfc42d3de7f8": {"__data__": {"id_": "9f499df6-d150-4089-bd1e-dfc42d3de7f8", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.28, para 2](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5e488833-4b0f-4c95-99b9-35dea3200ab5", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.28, para 2](https://elifesciences.org/articles/95135)"}, "hash": "daf8c6e9aecb3eb20f57d01dc1766e9c680dcdfd9a332d2fd5cd83a35d883535", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "), has been developed which allows these concise network templates to be described and multiple instances of networks to be generated, and facilitates interaction with simulation platforms and efficient serialization formats.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 225, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ca5c0069-dd83-4887-9942-3eaec9652514": {"__data__": {"id_": "ca5c0069-dd83-4887-9942-3eaec9652514", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.28, para 3](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d310a11f-dc88-4215-b534-09d09a6b407f", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.28, para 3](https://elifesciences.org/articles/95135)"}, "hash": "1f517f1e4bb4a72e8ea6ca7e471ef9eef3609f5f27baea4a6a50fd897fe7e370", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "As discoveries and insights in neuroscience inform machine learning and visa versa, there is an increasing need to develop a common framework for describing both biological and artificial neural networks. Model Description Format (MDF) has been developed to address this (Gleeson et al., 2023). This initiative has developed a standardized format, along with a Python API, which allows the specification of artificial neural networks (e.g. Convolutional Neural Networks, Recurrent Neural Networks) and biological neurons using the same underlying entities. Support for mapping MDF to/from NeuroMLv2/LEMS has been included from the start. This work will enable deeper integration of computational neuroscience and 'brain-inspired' networks in Artificial Intelligence (AI).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 771, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "22398d0b-c03b-44d9-9d5e-0e7659f6fbd6": {"__data__": {"id_": "22398d0b-c03b-44d9-9d5e-0e7659f6fbd6", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.28, para 4](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ee5ad5c8-8a2c-4b6b-bfbd-16ccf923d2fa", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.28, para 4](https://elifesciences.org/articles/95135)"}, "hash": "fb54367a8d40b4b08e5fd2507865b217e8c94fe035be6ad747b2fe4db8a5c0b3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Conclusion and vision for the future", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 39, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8d2db34f-47ad-4208-b3c7-329f10eecb30": {"__data__": {"id_": "8d2db34f-47ad-4208-b3c7-329f10eecb30", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.28, para 5](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5a42e9f4-27f1-466e-b1db-9a8e335aaa97", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.28, para 5](https://elifesciences.org/articles/95135)"}, "hash": "ca6b1a30399b5e5b8980d67f8e14e5f27e7d3bd98eca550b97792f4a8e4549e3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "NeuroMLv2 is already a mature community standard that provides a framework for standardizing biologically detailed neuronal network models. By providing a stable, common framework defining the essential entities required for biologically detailed neuronal modeling, NeuroML has spawned an ecosystem of tools that span all stages of the model development life cycle. In the short term, we envision the functionality of NeuroML to expand further and for new online resources that encourage the construction of FAIR models using pyNeuroML to be taken up by the community. The NeuroML development team are also beginning to explore how to combine NeuroML-based circuit models with musculo-skeletal simulations to enable models of the neural control of behavior. In the longer term, developing seamless interfaces between NeuroML and other domain specific standards will enable the development of more holistic models of the neural control of body systems across a wide range of organisms, as well as greater exchange of models and insights between computational neuroscience and AI.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1078, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e479b9b2-7b10-4bb8-926f-bfef3f6a2fa0": {"__data__": {"id_": "e479b9b2-7b10-4bb8-926f-bfef3f6a2fa0", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.28, para 6](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c9e4d7c7-c4c8-4221-879f-dd1d2754e361", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.28, para 6](https://elifesciences.org/articles/95135)"}, "hash": "077e018db3af45c778c3c6eec36e73eb3259af6a5716f9e1ed7fc15268546d06", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Materials and methods", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 23, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0c16e6fa-3211-4a20-bba3-ca7d5f7b1bbd": {"__data__": {"id_": "0c16e6fa-3211-4a20-bba3-ca7d5f7b1bbd", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.28, para 7](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8e5ab851-0398-43af-af74-82ba0121e066", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.28, para 7](https://elifesciences.org/articles/95135)"}, "hash": "d0ea3eb426b5590a785d1f164afbbc689605100e0ecd45d0d6caf79a56984a68", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "NeuroMLv2 is formally specified by the NeuroMLv2 XML schema, which defines the allowed structure of XML files which comply to the standard, and the LEMS ComponentType definitions, which define the internal state variables of the underlying elements, providing a machine-readable specification of the time evolution of model components. The specification is backed up by a suite of software tools that support the model life cycle and the accompanying usage and development documentation.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 487, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f2075d86-56b5-4bb9-8f04-03909a960dd8": {"__data__": {"id_": "f2075d86-56b5-4bb9-8f04-03909a960dd8", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.28, para 8](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f2dc72ea-9e3e-4878-9c87-2b66e60aebac", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.28, para 8](https://elifesciences.org/articles/95135)"}, "hash": "800e6ca443eb53070e2f1c4f86bf2c1c3cf28deea9f67050ee940809890f50c4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We illustrate the key parts of this framework using the *HindmarshRose cell model (Hindmarsh and Rose, 1984; Figure 11)*, which as an abstract point neuron model, serves as an appropriate simple NeuroMLv2 ComponentType.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 219, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "908df3c1-e6ec-4864-bdcb-9464686c1a0c": {"__data__": {"id_": "908df3c1-e6ec-4864-bdcb-9464686c1a0c", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.28, para 9](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ae5b14e3-d431-4a4e-b998-23ffa3958e3f", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.28, para 9](https://elifesciences.org/articles/95135)"}, "hash": "7df9150c3326551aba8f12af50d3b58a3fb3797902e32e432c90aecea73f47c8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## The NeuroML XML Schema", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 25, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c0dead0d-ffaf-4031-a5b4-24ceadae5159": {"__data__": {"id_": "c0dead0d-ffaf-4031-a5b4-24ceadae5159", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.28, para 10](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "404d5c9b-afce-4f41-ae1d-366e149f6935", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.28, para 10](https://elifesciences.org/articles/95135)"}, "hash": "1b6ce1476ca2999787576d1985daed1c38eadce508444115b2ad48cfb015a0cd", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We begin with the NeuroMLv2 standard. The standard consists of two parts, each serving different functions:", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 107, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e6d2256e-1b2a-4dff-a207-74135be19339": {"__data__": {"id_": "e6d2256e-1b2a-4dff-a207-74135be19339", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.28, para 11](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "411d02f9-5010-4b4c-baac-614e4ab3345c", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.28, para 11](https://elifesciences.org/articles/95135)"}, "hash": "514fa2e5b99d4f630387ddda3e145e24b9f62e4a88d3c64234b2c0d9c39c6ace", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "1. the NeuroMLv2 XML schema\n2. corresponding LEMS component type definitions", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 76, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c59d204d-d776-48d6-9318-b2d2953d95dc": {"__data__": {"id_": "c59d204d-d776-48d6-9318-b2d2953d95dc", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.28, para 12](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5a8b44ea-4b28-4e4a-946f-599a0084ed84", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.28, para 12](https://elifesciences.org/articles/95135)"}, "hash": "45a4641777c09db9dd8dc470ecf07d929a6f17743f44aca16aba05609e40b71f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The NeuroMLv2 schema is a language independent data model that constrains the structure of a NeuroMLv2 model description. The NeuroML schema is formally described as an XML Schema document (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 190, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "39ffaf56-3039-4319-a49f-a8795551977c": {"__data__": {"id_": "39ffaf56-3039-4319-a49f-a8795551977c", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.28, para 13](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "10462e59-d1c5-4820-8143-de1887930ea0", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.28, para 13](https://elifesciences.org/articles/95135)"}, "hash": "9f133b963d02efced3c4c0c3f52fdad6b65da5701fd41132c769de3f443afa71", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ") in the XML Schema Definition (XSD) format, a recommendation of the World Wide Web Consortium (W3C) (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 102, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d27548a7-3efd-492f-8c76-536d37a34bc3": {"__data__": {"id_": "d27548a7-3efd-492f-8c76-536d37a34bc3", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.28, para 14](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "087828e4-a840-4a73-b96b-3b8e56908968", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.28, para 14](https://elifesciences.org/articles/95135)"}, "hash": "fe6a678a5ff435db41a85e07fec966ee87dfb6c52caf7d6225ec18cf6f93458c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "). An XML document that claims to conform to a particular schema can be *validated* against the schema. All NeuroMLv2 model descriptions can, therefore, be validated against the NeuroMLv2 schema.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 195, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7a0ff500-74bc-4a43-b2cc-106f11e37f2e": {"__data__": {"id_": "7a0ff500-74bc-4a43-b2cc-106f11e37f2e", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.28, para 15](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "97b8eb3a-4f74-48f0-9bf2-b779e8d4293e", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.28, para 15](https://elifesciences.org/articles/95135)"}, "hash": "ba9d2dbf720abad5b735a92fcaed7b2af7fb46dc7c9bd18933b80c24288f13db", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135 28 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 94, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1e132974-f8cc-4327-9e69-1b8c09295d84": {"__data__": {"id_": "1e132974-f8cc-4327-9e69-1b8c09295d84", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.29, para 3](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bef68fd0-f53f-4148-bbaa-06e05d459ceb", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.29, para 3](https://elifesciences.org/articles/95135)"}, "hash": "20978077b0af0c89ee1522abafb1275abc8936faabbfbb92d62f32a8f23388a8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**b.**\nThe image shows a line graph of membrane potential (V) over time (s). The graph displays regular bursting activity, with clusters of rapid spikes followed by quiescent periods. The membrane potential oscillates between approximately -0.06 V and 0.06 V.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 259, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6a01b744-d1b8-4f4f-9c33-09a3b6817f85": {"__data__": {"id_": "6a01b744-d1b8-4f4f-9c33-09a3b6817f85", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.29, para 4](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2e1aac23-4d17-4039-937b-f8cc3ec88f56", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.29, para 4](https://elifesciences.org/articles/95135)"}, "hash": "78d5d504a4f42d186e3e35bb848acf0a0fbed7b5cb32d8b69ffb47bcc3b19dc2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Figure 11.** Example model description of a HindmarshRose1984Cell NeuroML component. **(a)** XML serialization of the model description containing the main hindmarshRose1984Cell element with a set of parameters which result in regular bursting. A current clamp stimulus is applied using a pulseGenerator, and a population of one cell is added with this in a network. This XML can be validated against the NeuroML Schema. **(b)** Membrane potentials generated from a simulation of the model in **(a)**. The LEMS simulation file to execute this is shown in **Figure 15**. The code used in this example is available here:", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 620, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b73cff10-8874-49f6-8649-83814cc05e75": {"__data__": {"id_": "b73cff10-8874-49f6-8649-83814cc05e75", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.29, para 5](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "30a7c895-b8b0-414e-b39e-7bc6698cefd5", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.29, para 5](https://elifesciences.org/articles/95135)"}, "hash": "376240b066ab8c810cfc06d1771bc118a0b79e7b5cdb30643057e0fbd0534155", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ".", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7e2166df-2b88-4ca6-af76-ab9af48c559e": {"__data__": {"id_": "7e2166df-2b88-4ca6-af76-ab9af48c559e", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.29, para 6](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a6ad47a3-3583-42fd-a55a-a018feacb056", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.29, para 6](https://elifesciences.org/articles/95135)"}, "hash": "3786d288d71acbd41e2d3f87df611a68982dc98addb0993e5a8d00a1c96015e0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The basic building blocks of an XSD schema are \u2018simple\u2019 or \u2018complex\u2019 types and their \u2018attributes.\u2019 All types are created as \u2018extensions\u2019 or \u2018restrictions\u2019 of other types. Complex types may contain other types and attributes whereas simple types may not. **Figure 12** shows some example types defined in the NeuroMLv2 schema. For example, the `Nml2Quantity_none` simple type restricts the in-built \u2018string\u2019 type using a regular expression \u2018pattern\u2019 that limits what string values it can contain. The type is `Nml2Quantity_none` is to be used for unit-less quantities (e.g. 3, 6.7, \u20131.1e-5) and the restriction pattern for translates to \u2018a string that may start with a hyphen (negative sign), followed by any number of numerical characters (potentially containing a decimal point) and a string containing capital or small \u2018e\u2019 (to specify the exponent).\u2019 The restriction pattern for the `Nml2Quantity_voltage` type is similar, but must be followed by a \u2018V\u2019 or \u2018mV.\u2019 In this way, the restriction ensures that a value of type \u2018Nml2Quantity\\_voltage\u2019 represents a physical voltage quantity with units \u2018V\u2019 (volt) or \u2018mV\u2019 (millivolt). Furthermore, a NeuroMLv2 model description that uses a voltage value that does not match this pattern, for example \u20180.5 s,\u2019 will be invalid.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1268, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "eb8cc754-a73a-44b1-946f-fb7a1da2bcc2": {"__data__": {"id_": "eb8cc754-a73a-44b1-946f-fb7a1da2bcc2", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.29, para 7](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "11c2606e-68f6-43f2-af4d-4d3b82530ffb", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.29, para 7](https://elifesciences.org/articles/95135)"}, "hash": "0885f9fb8d9647ed0be0d8fc71104d2fa3232ab02b7493300914856c6caa320b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The example of a complex type in **Figure 12** is the `HindmarshRose1984Cell` type that extends the `BaseCellMembPotCap` complex type (the base type for any cell producing a membrane potential", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 192, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8b1ef5af-0894-46f9-8977-f59d19fbe59d": {"__data__": {"id_": "8b1ef5af-0894-46f9-8977-f59d19fbe59d", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.29, para 8](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4a4c3bea-4d6b-4ecf-ba35-e5d1123f5def", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.29, para 8](https://elifesciences.org/articles/95135)"}, "hash": "34919a68a0877192eacd20ec8ebf6fe5688d074e97496ed644255e1350e84ecf", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135 29 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 94, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d93cb864-3ba3-4c37-92b7-ff190344903f": {"__data__": {"id_": "d93cb864-3ba3-4c37-92b7-ff190344903f", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.30, para 1](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4591b367-c647-4e7c-abd0-120f6080f107", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.30, para 1](https://elifesciences.org/articles/95135)"}, "hash": "eba462d39b84bfb3796169356ed2b846e69757005e0cfe5c84e341bc49fbebca", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "```xml\n \n \n  \n \n\n \n \n  \n \n\n \n  The Hindmarsh Rose model is a simplified point cell model which\n    captures complex firing patterns of single neurons, such as\n    periodic and chaotic bursting...\n  \n \n \n  \n   \n   \n   \n   \n   \n   \n   \n   \n   \n   \n   \n  \n \n\n```", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 259, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "11896e37-d914-486d-9c94-2d689fc9b5ef": {"__data__": {"id_": "11896e37-d914-486d-9c94-2d689fc9b5ef", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.30, para 2](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4930c7d2-38c1-421b-88c8-64a905aa9d12", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.30, para 2](https://elifesciences.org/articles/95135)"}, "hash": "0181d2ed685e7dc6ef13d14ce6123e4c2fbcd5b80bca90f5889ce55e12ee8ba7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Figure 12.** Type definitions taken from the NeuroMLv2 schema (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 65, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e1b95c18-86ef-4f9a-9eae-96dd4799d22e": {"__data__": {"id_": "e1b95c18-86ef-4f9a-9eae-96dd4799d22e", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.30, para 3](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "de743557-7db0-450d-9bce-f7142b4f9e78", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.30, para 3](https://elifesciences.org/articles/95135)"}, "hash": "68e5f36a54af8b5429bfc0118481505d844de3a46ebf6c267d182967453ec7b1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ") which describes the structure of NeuroMLv2 elements. Top: \u2018simple\u2019 types may not include other elements or attributes. Here, the `Nml2Quantity_none` and `Nml2Quantity_voltage` types define restrictions on the default string type to limit what strings can be used as valid values for attributes of these types. Bottom: example of a \u2018complex\u2019 type, the HindmarshRose cell model (**Hindmarsh and Rose, 1984**), that can also include other elements of other types, and extend other types.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 486, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "51df64b6-3bb4-49c8-a3cc-2f12b04955ad": {"__data__": {"id_": "51df64b6-3bb4-49c8-a3cc-2f12b04955ad", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.30, para 4](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6e9d931e-c11d-4204-b603-66635a2cccb4", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.30, para 4](https://elifesciences.org/articles/95135)"}, "hash": "50dfa21f09ef255e02bf812bca645eae38d4ba83da265afcb358cc1dce016e66", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "v with a capacitance parameter `C`), and defines new \u2018required\u2019 (compulsory) attributes. These attributes are of simple types\u2014these are all unit-less quantities apart from `v_scaling`, which has dimension voltage. Note that inherited attributes are not re-listed in the complex type definition\u2014the compulsory capacitance attribute, `C`, is inherited here from `BaseCellMembPotCap`.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 381, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f64ac74e-4ee4-404a-8d20-1da0a1b42c49": {"__data__": {"id_": "f64ac74e-4ee4-404a-8d20-1da0a1b42c49", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.30, para 5](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "819fa6d7-768a-4f3c-ad4f-34093de3abaf", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.30, para 5](https://elifesciences.org/articles/95135)"}, "hash": "0feb3691ca2a33700c8629d19da6033bf2b1f8f7029433665a84353a1616c378", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The NeuroMLv2 schema serves multiple critical functions. A variety of tools and libraries support the validation of files against XSD schema definitions. Therefore, the NeuroMLv2 schema enables the validation of model descriptions\u2014model structure, parameters, parameter values and their units, cardinality, element positioning in the model hierarchy (level 1 validation in **Figure 7**)\u2014prior to simulation. XSD schema definitions, as language independent data models, also allow the generation of APIs in different languages. More information on how APIs in different languages are generated using the NeuroMLv2 XSD schema definition is provided in later sections.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 665, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8d9d0f16-cc44-46c3-8fd0-884086c655d7": {"__data__": {"id_": "8d9d0f16-cc44-46c3-8fd0-884086c655d7", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.30, para 6](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4c53a18e-9d1d-47d1-8c6f-e773f568229e", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.30, para 6](https://elifesciences.org/articles/95135)"}, "hash": "5ed4f25c902d955ef3d550689fdc36ecfd4696a9b35cc81f1aab1c9fb4949271", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The NeuroMLv2 XSD schema is also released and maintained as a versioned artifact, similar to the software packages. The current version is 2.3, and can be found in the NeuroML2 repository on GitHub (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 199, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "553fb3f4-b6e4-4b21-9c6f-3daecc046345": {"__data__": {"id_": "553fb3f4-b6e4-4b21-9c6f-3daecc046345", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.30, para 7](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a7851b3c-8bdd-4c6e-a33a-1695364858b9", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.30, para 7](https://elifesciences.org/articles/95135)"}, "hash": "c4335465cc99e3ba418a1f96192c7e3dd61e0ed46ef5b52b7fb3c4e31a794c96", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ").", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fb2f4ceb-c41b-42bf-9818-905d2cd89b32": {"__data__": {"id_": "fb2f4ceb-c41b-42bf-9818-905d2cd89b32", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.30, para 8](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6fd8fd3f-a00a-4250-a6d0-bdaa9cab028a", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.30, para 8](https://elifesciences.org/articles/95135)"}, "hash": "e21deb4b12774d43a341669c94ca6f763372d8caea118c4b44a1bc956a3d660a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### LEMS ComponentType definitions", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 34, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "66f9bc4d-1510-4e9f-a613-a58134105667": {"__data__": {"id_": "66f9bc4d-1510-4e9f-a613-a58134105667", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.30, para 9](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4630cd17-8910-4ca0-913d-2a9942538fdf", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.30, para 9](https://elifesciences.org/articles/95135)"}, "hash": "7fb652c6328d6863b843dcaac812339a7cb09fb90acbe11d3f3a373407edcece", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The second part of the NeuroMLv2 standard consists of the corresponding LEMS ComponentType definitions. Whereas the XSD Schema describes the *structure* of a NeuroMLv2 model description, the LEMS ComponentType definitions formally describe the dynamics of the model elements.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 275, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "19f2277c-18ee-4e95-aabc-62b724666a73": {"__data__": {"id_": "19f2277c-18ee-4e95-aabc-62b724666a73", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.30, para 10](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5a651dd8-3bab-4043-97cb-52dda7d63cd6", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.30, para 10](https://elifesciences.org/articles/95135)"}, "hash": "c27bf99c3fd40231e78e650af35e9f2823cf096f14310cd01edd1387dbf02526", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135 30 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 94, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "882ccb20-c051-4526-abbb-3c2912db8bf1": {"__data__": {"id_": "882ccb20-c051-4526-abbb-3c2912db8bf1", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.31, para 1](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "91164fcc-c2ae-4c0d-9625-3d7c1c72fbac", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.31, para 1](https://elifesciences.org/articles/95135)"}, "hash": "59ef0e4575058bbf3e2e891b0238a259b056f4fe08a77655c526176e155b5509", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "LEMS (**Cannon et al., 2014**) is a domain independent general purpose machine-readable language for describing models and their simulations. A complete description of LEMS is provided in **Cannon et al., 2014** and in our documentation (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 238, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "bfef944b-68e8-48b6-bb9d-141e34216aa2": {"__data__": {"id_": "bfef944b-68e8-48b6-bb9d-141e34216aa2", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.31, para 2](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bc9dcb1a-3fb9-43f1-a1fc-686f3a1d878c", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.31, para 2](https://elifesciences.org/articles/95135)"}, "hash": "bad63bcde8b023226fcfceac3727a171fdec9f863ccbf6e8c9ebe907150f006c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "). Here, we limit ourselves to a short summary necessary for understanding the NeuroMLv2 `ComponentType` definitions.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 117, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e63aae8a-3c10-4b8f-adb3-42928e8bd842": {"__data__": {"id_": "e63aae8a-3c10-4b8f-adb3-42928e8bd842", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.31, para 3](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b1805497-5980-43b0-a57f-faa63adfae14", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.31, para 3](https://elifesciences.org/articles/95135)"}, "hash": "f5968b5f7850cd600e6fedb05ea5476f52c6a9b2571c8185e45dc04fd02cfa30", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "LEMS allows the definition of new model types called `ComponentTypes`. These are formal descriptions of how a generic model element of that type behaves (the 'dynamics'), *independent of the specific set of parameters in any instance*. To describe the dynamics, such descriptions must list any necessary parameters that are required, as well as the time-varying state variables. The dimensions of these parameters and state variables must be specified, and any expressions involving them must be dimensionally consistent. An instance of such a generic model is termed a `Component` and can be instantiated from a `ComponentType` by providing the necessary parameters. One can think of `ComponentTypes` as user defined data types similar to 'classes' in many programming languages and `Components` as 'objects' of these types with particular sets of parameters. Types in LEMS can also extend other types, enabling the construction of a hierarchical library of types. In addition, since LEMS is designed for model simulation, `ComponentType` definitions also include other simulation-related features such as `Exposures`, specifying quantities that may be accessed/recorded by users.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1181, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0ab934c7-e92c-4fa0-aa01-bb357517dc81": {"__data__": {"id_": "0ab934c7-e92c-4fa0-aa01-bb357517dc81", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.31, para 4](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3b483c20-1d88-4714-b517-6bd53c330379", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.31, para 4](https://elifesciences.org/articles/95135)"}, "hash": "65856ddbd92979892495ab8df690d71f56c27797a2e7e7751bc1dda5770c28aa", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "For model elements included in the NeuroML standard, there is a one-to-one mapping between types specified in the NeuroML XSD schema and LEMS `ComponentTypes`, with the same parameters specified in each. The addition of new model elements to the NeuroML standard, therefore, requires the addition of new type definitions to both the XSD schema and the LEMS definitions. New user defined `ComponentTypes`, nevertheless, can be defined in LEMS and used freely in models, and these do not need to be added to the standard before use. The only limitation here is that new user defined `ComponentTypes` cannot be validated against the NeuroML schema since their type definitions will not be included there.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 701, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e40ffd67-5ec7-416c-837b-88bf3c4cb72f": {"__data__": {"id_": "e40ffd67-5ec7-416c-837b-88bf3c4cb72f", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.31, para 5](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1f786957-bcc4-4081-9f95-73310f5556b3", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.31, para 5](https://elifesciences.org/articles/95135)"}, "hash": "76facc09bc8e95c273849601054bc5e9bb7f13e13769b903889c43512db9137e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Figure 13** shows the `ComponentType` definition for the `HindmarshRose1984Cell` model element. Here, the `HindmarshRose1984Cell` `ComponentType` extends `baseCellMembPotCap` and inherits its elements. The `ComponentType` includes parameters that users must provide when creating a new instance (component): *a, b, c, d, r, v, x1, v\\_scaling*.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 345, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d866d875-81af-4930-8909-2bf3b7bce890": {"__data__": {"id_": "d866d875-81af-4930-8909-2bf3b7bce890", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.31, para 6](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "35c9e115-5ee3-4ef3-98a2-890dd56e2a9a", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.31, para 6](https://elifesciences.org/articles/95135)"}, "hash": "a1a17858252a76f030bc487e11c8f39a7ea87b5a69cb1fc12bf860ade0c43381", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Other parameters, *x0, y0*, and *z0* are used to initialize the three state variables of the model, *x, y, z*. *x* is the proxy for the membrane potential of the cell used in the original formulation of the model (**Hindmarsh and Rose, 1984**) and is here scaled by a factor *v\\_scaled* to expose a more physiological value for the membrane potential of the cell in `StateVariable` *v*. A `Constant`, MSEC, is defined to hold the value of 1 ms for use in the `ComponentType`. Next, an `Attachment` enables the addition of entities that would provide external inputs to the `ComponentType`. Here, synapses are `Attachments` of the type `basePointCurrent` and provide synaptic current input to this `ComponentType`.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 713, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d5e6ce08-5e89-4f41-b81f-b1e4b01fe39c": {"__data__": {"id_": "d5e6ce08-5e89-4f41-b81f-b1e4b01fe39c", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.31, para 7](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "66f81937-798f-4d41-82f9-97ddd504df71", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.31, para 7](https://elifesciences.org/articles/95135)"}, "hash": "1baf1f1bd8d03077d8cb973b3c07be2fb7780f142722cc2906c38323711acc17", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The `Dynamics` block lists the mathematical formalism required to simulate the `ComponentType`. By default, variables defined in the `Dynamics` block are private, i.e., they are not visible outside the `ComponentType`. To make these visible to other `ComponentTypes` and to allow users to record them, they must be connected to `Exposures`. Exposures for this `ComponentType` include the three state variables and also the internal derived variables, which while not used by other components, are useful in inspecting the `ComponentType` and its dynamics. An extra exposure, *spiking*, is added to allow other NeuroML components access to the spiking state of the cell that will be determined in the `Dynamics` block.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 717, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "28398445-09fb-4661-acaa-a67d8fb0ca53": {"__data__": {"id_": "28398445-09fb-4661-acaa-a67d8fb0ca53", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.31, para 8](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a3d3a0d7-210c-4f37-a911-58b06aa156ff", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.31, para 8](https://elifesciences.org/articles/95135)"}, "hash": "317fa0e7e6a0eab1433f628ae54afbc855ff76d0d619f8cc9319ca48ce411598", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "`StateVariable` definitions are followed by `DerivedVariables`, variables whose values depend on other variables but are not time derivatives (which are handled separately in `TimeDerivative` blocks (below)). The total synaptic current, *iSyn*, is a summation of all the synaptic currents, *i* received by the synapses that may be attached on to this `ComponentType`. The `synapse[*]/i` value of the select field tells LEMS to collect all the `i` exposures from any synapses `Attachments`, and the `add` value of the reduce field tells LEMS to sum the multiple values. As noted, *x* is a scaled version of the membrane potential variable, *v*. This is followed by the three derived variables, *phi, chi, rho* where:", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 715, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "61d4d0a4-95e0-4a0a-8d3e-1e6712d789a6": {"__data__": {"id_": "61d4d0a4-95e0-4a0a-8d3e-1e6712d789a6", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.31, para 11](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0f7cf7ed-8f93-4342-89c8-62bd4061d757", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.31, para 11](https://elifesciences.org/articles/95135)"}, "hash": "0e957fc33496a96a71e5145407d1c486266b08bee8a610781eaf9a20e1205e11", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135 31 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 94, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d3521edd-fc98-4a9e-b99c-64fc9a95f9e3": {"__data__": {"id_": "d3521edd-fc98-4a9e-b99c-64fc9a95f9e3", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.32, para 1](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "029ab280-a1ba-4077-a118-d28a9efc3c06", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.32, para 1](https://elifesciences.org/articles/95135)"}, "hash": "4573ac960156bfd71c9b3eba283da5067c6b55299a9b8852309585cbf7c92d00", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "```xml\n\n    \n    \n    \n    \n    \n    \n    \n    \n\n    \n    \n    \n    \n\n    \n\n    \n\n    \n    \n    \n    \n    \n    \n    \n    \n        \n        \n        \n        \n\n        \n        \n        \n        \n        \n        \n\n        \n        \n        \n\n        \n            \n            \n            \n        \n        \n            \n            \n        \n        \n            \n        \n    \n\n```", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 383, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "55ae2472-34ac-4d3a-8469-1cc4ec8c8138": {"__data__": {"id_": "55ae2472-34ac-4d3a-8469-1cc4ec8c8138", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.32, para 2](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "96f305ff-281e-4d5c-a203-4f5e4dd5f628", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.32, para 2](https://elifesciences.org/articles/95135)"}, "hash": "f444b5f9189d369930fb41a09f993b31c2a39878e5cc292c68de4ce9b3153198", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Figure 13.** LEMS ComponentType definition of the HindmarshRose cell model (*Hindmarsh and Rose, 1984*,", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 105, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ad97977e-6931-40ca-9cd8-0eef9ef2fc13": {"__data__": {"id_": "ad97977e-6931-40ca-9cd8-0eef9ef2fc13", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.32, para 3](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3c48047c-b62d-47bb-99c2-8e3fe5e9123d", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.32, para 3](https://elifesciences.org/articles/95135)"}, "hash": "b1ccfd172c266e4c6de70a85463c52b1b5cf1047a507588567aa37488141b95f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ").", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0408d286-ba48-4e1a-bbb5-de284172f9f1": {"__data__": {"id_": "0408d286-ba48-4e1a-bbb5-de284172f9f1", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.32, para 5](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8c4d5141-da2d-4188-8467-9269a6003207", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.32, para 5](https://elifesciences.org/articles/95135)"}, "hash": "143f5070d41b7bcbd5c39fa0b8f143b5bbdbaaa83c9cc31c80770716ce6fa52e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The total membrane potential of the cell, *iMemb*, is calculated as the sum of the capacitive current and the synaptic current:", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 127, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "93421a37-9829-4e7e-b627-f310c26f642f": {"__data__": {"id_": "93421a37-9829-4e7e-b627-f310c26f642f", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.32, para 7](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1122bcee-8e1c-47fa-a457-907f335cf495", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.32, para 7](https://elifesciences.org/articles/95135)"}, "hash": "b7508227bb684250da1d6d4a4ce1a8cf78cb5f978089083c970bb7e6970a1745", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135 32 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 94, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8f57d407-4092-4ba8-a6a1-5a6faa012952": {"__data__": {"id_": "8f57d407-4092-4ba8-a6a1-5a6faa012952", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.33, para 1](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "28601ecc-9bb5-4744-981c-fdd40b6879da", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.33, para 1](https://elifesciences.org/articles/95135)"}, "hash": "f8be6227c1b2ec55298306dbb33520b1b93a2700e33ce42d169e56c67a1842fd", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "v, y, z are TimeDerivatives, with the 'value' representing the rate of change of each variable:", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 95, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ddc02ed7-f3c8-4700-911b-46ee465d0bdb": {"__data__": {"id_": "ddc02ed7-f3c8-4700-911b-46ee465d0bdb", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.33, para 2](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "78feca74-76ed-4f8a-9c63-74298867f762", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.33, para 2](https://elifesciences.org/articles/95135)"}, "hash": "468954f2d66c4b8798b98144c25c0841027ceb215691dad39a6c8bf50bff3521", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "dv/dt = iMemb/C \\tag{5}\ndy/dt = chi/MSEC \\tag{6}\ndz/dt = (r \\times rho)/MSEC \\tag{7}", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 84, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "aed12b53-1c0c-4c9f-b96f-f189ffb1dfa3": {"__data__": {"id_": "aed12b53-1c0c-4c9f-b96f-f189ffb1dfa3", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.33, para 3](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ce8c7625-a287-4312-8172-9308e5df4937", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.33, para 3](https://elifesciences.org/articles/95135)"}, "hash": "1b92485773f29f83dead7520b5363ea74c3d1da388e8c7a5aa0b2f9cfa000a4e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The final few blocks set the initial state of the component (OnStart),", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 70, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7320502d-d4e6-4fe0-a697-56548c7fc0cb": {"__data__": {"id_": "7320502d-d4e6-4fe0-a697-56548c7fc0cb", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.33, para 4](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4edcd6a8-ccbf-4dd8-8266-94dcb091bb7d", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.33, para 4](https://elifesciences.org/articles/95135)"}, "hash": "8f7d670c0fb46784027a182cd071f9b149df6b88339b590bb5b9454541703acb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "v = x0 \\times v\\_scaling \\tag{8}\ny = y0 \\tag{9}\nz = z0 \\tag{10}", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 63, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "bbf7abd2-a2e7-4de5-b99c-8f2fa3ea1255": {"__data__": {"id_": "bbf7abd2-a2e7-4de5-b99c-8f2fa3ea1255", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.33, para 5](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "37b8b7a7-0740-4607-83b6-0093dc517108", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.33, para 5](https://elifesciences.org/articles/95135)"}, "hash": "666edc722008d5461ec4defbd941f4a276e40f092617607bb2d85bc8ef2e991b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "and define conditional expressions to set the spiking state of the cell:", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 72, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5dae099b-370b-4f95-a9bc-1794065b2ff9": {"__data__": {"id_": "5dae099b-370b-4f95-a9bc-1794065b2ff9", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.33, para 6](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9b6ea15e-4b2d-4455-a9b0-c79d5f5966c0", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.33, para 6](https://elifesciences.org/articles/95135)"}, "hash": "e159f01cb4b2e432f37e090de0f3e7b557452a35fbf9ef5279b71d39aefb8bdd", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "spiking = \\begin{cases} 1 & if  (v > 0) \\wedge (spiking < 0.5) \\ 0 & if  (v < 0) \\end{cases} \\tag{11}", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 101, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2dec09ce-d07a-406d-a0d6-d724f77049f9": {"__data__": {"id_": "2dec09ce-d07a-406d-a0d6-d724f77049f9", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.33, para 7](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1d38dccc-9e26-474d-8209-af3b32bd49c4", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.33, para 7](https://elifesciences.org/articles/95135)"}, "hash": "8da94e21222c62e8d06ae679b9781b24ef4e3d609e8b39e3102af227874b0adc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Both the XSD schema and the LEMS `ComponentType` definitions enable model validation. However, despite some overlap, they support different types of validation. Whereas the XSD schema allows for the validation of model descriptions (e.g. the XML files), the LEMS `ComponentType` definitions enable validation of *model instances*, i.e., the 'runnable' instances of models that are constructed once components have been created by instantiating `ComponentTypes` with the necessary parameters, and various attachments created between source and target components. A model description may be used to create many different model instances for simulation. Indeed, it is common practice to run models that include stochasticity with different seeds for random number generators to verify the robustness of simulation results. Thus, the validation of dimensions and units that LEMS carries out is done only after a runnable instance of a model has been created.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 954, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "61b71f36-f051-44de-9ae8-16293038589d": {"__data__": {"id_": "61b71f36-f051-44de-9ae8-16293038589d", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.33, para 8](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a016d3a3-ae21-4a6e-a022-37b1ffda6fca", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.33, para 8](https://elifesciences.org/articles/95135)"}, "hash": "763ef576cee1175b02142d0ac1bde93453be22ffd57bdd9b46599bb41421b8e7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The LEMS `ComponentType` definitions for NeuroMLv2 are also maintained as versioned files that are updated along with the XSD schema. These can also be seen in the NeuroMLv2 GitHub repository (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 193, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9f7c0d80-552f-4c48-9d29-a2d98052a1d3": {"__data__": {"id_": "9f7c0d80-552f-4c48-9d29-a2d98052a1d3", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.33, para 9](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d6ee4f29-a98c-49f3-ae1f-a50108f8187c", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.33, para 9](https://elifesciences.org/articles/95135)"}, "hash": "62e49270ae62b554385eb89dafd5bb344cefa5e008c3f8ed0f31cf91c10c2dfc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "). An index of the `ComponentTypes` included in version 2.3 of the NeuroML standard, with links to online documentation, is also provided in ***Tables 1 and 2***.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 162, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "43d7dd45-078a-4bc5-a7be-b3b1c6002776": {"__data__": {"id_": "43d7dd45-078a-4bc5-a7be-b3b1c6002776", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.33, para 10](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "07d0a754-09ba-405e-a26b-b8adc59b4e51", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.33, para 10](https://elifesciences.org/articles/95135)"}, "hash": "c2af0c511dec600c130d597e6435d861a782eb5aaf52a8993b4817f0fe6ddf53", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## NeuroML APIs", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 15, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6ba5bba6-78c6-4e15-9d8a-610504c7f5f8": {"__data__": {"id_": "6ba5bba6-78c6-4e15-9d8a-610504c7f5f8", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.33, para 11](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2060e65f-0f04-4d59-9c5e-0f82fdb96b87", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.33, para 11](https://elifesciences.org/articles/95135)"}, "hash": "49c5b15c65b0f148897a6fc597aceb862c645c3c68ab971d261cdce598434dd1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The NeuroMLv2 software stack relies on the NeuroML APIs that provide functionality to read, write, validate, and inspect NeuroML models. The APIs are programmatically generated from the machine readable XSD schema, thus ensuring that the class for defining a specific NeuroML element in a given language (e.g. Java) has the correct set of fields with the appropriate type (e.g. float or string) corresponding to the allowed parameters in the corresponding NeuroML element. NeuroMLv2 currently provides APIs in numerous languages\u2014Python (libNeuroML which is generated via generateDS (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 583, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e031305a-b539-4b61-b30f-3df6fac42d4f": {"__data__": {"id_": "e031305a-b539-4b61-b30f-3df6fac42d4f", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.33, para 14](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f44c0bb5-3cc1-4c4c-8b05-5c7e98db7a91", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.33, para 14](https://elifesciences.org/articles/95135)"}, "hash": "714eefe4be9bec44166ee4dcb93ef149ab7c9b3c22fb58b919b0de944b3e2c8a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ")) and MATLAB (NeuroMLToolbox which accesses the Java API from MATLAB), and APIs for other languages can also be easily generated as required. LEMS is also supported by a similar set of APIs\u2014PyLEMS in Python, and jLEMS in Java\u2014and since a NeuroMLv2 model description is a set of LEMS `Components`, the LEMS APIs also support them (e.g. the `hindmarshRose1984Cell` example in ***Figure 11*** could be loaded by jLEMS and treated as a LEMS `Component`).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 451, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6558e239-f7ae-4c1f-a29d-a1e5bd0f5747": {"__data__": {"id_": "6558e239-f7ae-4c1f-a29d-a1e5bd0f5747", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.33, para 15](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0949e5c5-47a7-4248-88c7-3e6ca5ea143b", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.33, para 15](https://elifesciences.org/articles/95135)"}, "hash": "ebf2d87964df32428d7236817cc9a177074a7424d2c3974c67dc2c9717557a22", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "***Figure 14*** shows the use of the NeuroML Python API to describe a model with one HindmarshRose cell. In Python, the instances of `ComponentTypes`, their `Components`, are represented as Python objects. The `hr0` Python variable stores the created `HindmarshRose1984Cell` component/object. This is added to a `Population` `pop0` in the `Network` `net`. The network also includes a `PulseGenerator` with amplitude 5 nA as an `ExplicitInput` that is targeted at the cell in the population. The model description is serialized to XML (***Figure 11***) and validated. Note that as the standard convention for classes in Python is to use capitalized names, `HindmarshRose1984Cell` is used in Python but is serialized as `` in the XML. Users can either share the Python script", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 773, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e3eb349b-2f7d-48cc-9e84-f43a1f0d3d9a": {"__data__": {"id_": "e3eb349b-2f7d-48cc-9e84-f43a1f0d3d9a", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.33, para 16](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4a0f78b6-0547-4474-b93d-fe80882c5c05", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.33, para 16](https://elifesciences.org/articles/95135)"}, "hash": "00e199a6c1e77dc5f1cf84f410a27ad56f36918653125f35e1c924633dfadb39", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135 33 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 94, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0d8386ca-de3c-4bd7-b799-9199fec87c27": {"__data__": {"id_": "0d8386ca-de3c-4bd7-b799-9199fec87c27", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.34, para 1](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "53a9c09e-5dc1-4237-8b47-03cc294ad2df", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.34, para 1](https://elifesciences.org/articles/95135)"}, "hash": "49af286784735450cc8326c2562797b1e2e2f4ace99c1e7b735c39211bea3f00", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "```python\n# Create a new HindmarshRose cell component with parameters for regular spiking\n\nnml_doc = component_factory(\"NeuroMLDocument\", id=\"HindmarshRoseNeuron\")\nhr0 = nml_doc.add(\"HindmarshRose1984Cell\", id=\"hr_regular\", a=\"1.0\", b=\"3.0\", c=\"-3.0\", d=\"5.0\",\n s=\"4.0\", x1=\"-1.3\", r=\"0.002\", x0=\"-1.1\", y0=\"-9\", z0=\"1.0\", C=\"28.57142857pF\",\n v_scaling=\"35.0mV\")\nnet = nml_doc.add(\"Network\", id=\"HRNet\", validate=False)\n\n# Create a population of cells (1 cell)\n\npop0 = net.add(\"Population\", id=\"HRPop0\", component=hr0.id, size=1)\n\n# Add external stimuli to the population\n\npg = nml_doc.add(\"PulseGenerator\", id=\"pulseGen_%i\" % 0, delay=\"0s\", duration=\"1000s\",\n amplitude=\"5nA\")\nexp_input = net.add(\"ExplicitInput\", target=\"%s[%i]\" % (pop0.id, 0), input=pg.id,\n destination=\"synapses\")\n\n# Save (serialize) the model to a file\n\nnml_file = 'hindmarshrose1984_single_cell_network.nml'\nwriters.NeuroMLWriter.write(nml_doc, nml_file)\n\n# Validate the model\n\nvalidate_neuroml2(nml_file)\n```", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 982, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5056b43b-1934-46c5-a358-322500ed2158": {"__data__": {"id_": "5056b43b-1934-46c5-a358-322500ed2158", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.34, para 2](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "da9a25e4-5207-4601-adef-597d4a777f50", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.34, para 2](https://elifesciences.org/articles/95135)"}, "hash": "896d20996b1b28a68c9f0ae350443c7863522d43345de845ab85392abcf39ae7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Figure 14.** Example model description of a HindmarshRose1984Cell NeuroML component in Python using parameters for regular bursting. This script generates the XML in **Figure 11**. The code used in this example is available here:", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 231, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d67df148-caa9-49b1-949b-a3d010c3c34e": {"__data__": {"id_": "d67df148-caa9-49b1-949b-a3d010c3c34e", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.34, para 3](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e48e8e41-0940-45fd-9860-1d55f76727c2", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.34, para 3](https://elifesciences.org/articles/95135)"}, "hash": "488b9644119deb28f5c33cbda2a7eb0cda6699c4970c6911112357ec7326b023", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ".", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b71699cd-4927-4aba-8aef-20cf5dc52ead": {"__data__": {"id_": "b71699cd-4927-4aba-8aef-20cf5dc52ead", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.34, para 4](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fff160cf-6c2b-43b1-9046-2f1eecbf4271", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.34, para 4](https://elifesciences.org/articles/95135)"}, "hash": "d8b6e38b5099482244adfac6c114be3390263d35dd8778c9df62b51ca7b090f1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "itself or share the XML serialization. Any valid XML serialization can be also loaded into a Python object model and modified.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 126, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "845bae1c-50d8-4c29-8d55-a8eab3580ae5": {"__data__": {"id_": "845bae1c-50d8-4c29-8d55-a8eab3580ae5", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.34, para 5](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7cdd94e6-4650-4513-af67-8b2c578ee343", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.34, para 5](https://elifesciences.org/articles/95135)"}, "hash": "b6a599504440d687c72fa6b7603edc2549134248d03f624f08d62a7207bc1a2b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "XML is the default serialization of NeuroML and all existing APIs can read and write the format (and it should be seen as a minimal requirement for new APIs to support XML). There is, however, an alternative HDF5 (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 214, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e036c990-9919-4505-a674-56f421c77eb6": {"__data__": {"id_": "e036c990-9919-4505-a674-56f421c77eb6", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.34, para 6](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5228356f-5ae8-4dd9-83b9-795fbc825656", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.34, para 6](https://elifesciences.org/articles/95135)"}, "hash": "c99b71188414eba36d530ccdf80f8eabd442644e3cbf340ea758bea45cc183fa", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ") based serialization of NeuroML files which is supported by both libNeuroML and the Java API, `org.neuroml.model` (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 116, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "62682927-2579-46d6-851e-fa445d6e2d9c": {"__data__": {"id_": "62682927-2579-46d6-851e-fa445d6e2d9c", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.34, para 7](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e2893163-0e6f-45b6-a7e1-fef977c55cf3", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.34, para 7](https://elifesciences.org/articles/95135)"}, "hash": "39a1445fa38ed6c1a8d49c9ce4fbe9125c72b4af113737e7f81bbd55e51f1eb4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "). This format is based on an efficient representation of cell positions and connectivity data as HDF5 data sets which can be serialized in compact binary format and loaded into memory for optimized access (e.g. as numpy arrays in libNeuroML). This reduces the size of the saved files for large-scale networks and speeds up loading/writing models eliminating the need to parse/generate large text files containing XML. Models serialized in this format can be loaded and transformed to simulator code in the same way as XML-based models by the Java and Python APIs.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 564, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "aac8d588-4694-47d1-9401-a4e2a5004761": {"__data__": {"id_": "aac8d588-4694-47d1-9401-a4e2a5004761", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.34, para 8](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e260ecb9-323c-4b7e-8830-457f1c7b2070", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.34, para 8](https://elifesciences.org/articles/95135)"}, "hash": "7d18d9db88ec32fb69c9a2b484c032a1160f1ffa03a972ea87185edf7f8e6b3b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Simulating NeuroML models", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 29, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9d2de8cd-3dce-4dea-892b-1f11e6cb71ab": {"__data__": {"id_": "9d2de8cd-3dce-4dea-892b-1f11e6cb71ab", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.34, para 9](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d877b604-a84c-4b55-adc6-4fcfd6441ce6", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.34, para 9](https://elifesciences.org/articles/95135)"}, "hash": "edc0d901bddeb066f043613e9d0dc8ec3b9155c81473ac9160829760e80d422e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The model description shown in **Figure 11** contains no information about how it is to be simulated, or on the dynamics of each model component. Providing this simulation information and linking in the `ComponentType` definition requires creating a LEMS file to fully specify the simulation. **Figure 15** shows the use of utilities included in the Python pyNeuroML package to describe a LEMS simulation of the HindmarshRose model defined in **Figure 11**. The `LEMSSimulation` object includes simulation specific information such as the duration of the simulation, the integration time step, and the seed value. It also allows the specification of files for the storage of data recorded from the simulation. In this example, we record the membrane potential, v, of our cell in its population, `HRPop0[0]`. Similar to the NeuroMLv2 model description, the simulation object can also be serialized to XML for storage and sharing (**Figure 15**, bottom).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 952, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "bec442af-2a1c-44ae-850f-5c4ec78dab5b": {"__data__": {"id_": "bec442af-2a1c-44ae-850f-5c4ec78dab5b", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.34, para 10](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ef4c3305-43b8-4761-abbe-43147e9cf476", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.34, para 10](https://elifesciences.org/articles/95135)"}, "hash": "30a8395e36e8e479fd5b57cc80c2e20dfdc9b27f1e21640d2da102752e163e5f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "As noted previously, NeuroML/LEMS model and simulation descriptions are machine readable and simulator independent and can be simulated by simulation engines using a multitude of strategies (**Figure 5**).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 205, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3819462a-fecf-4acc-b3ba-cc9dd8a5b3d2": {"__data__": {"id_": "3819462a-fecf-4acc-b3ba-cc9dd8a5b3d2", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.34, para 11](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "94650b36-d4d7-4a44-bac9-3fc51cf04896", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.34, para 11](https://elifesciences.org/articles/95135)"}, "hash": "5dd2217c5a086a52e024fd7e5146d5cdad0223ae1e74c7fece96a7cd10b37343", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The first category of tools consists of the reference NeuroML and LEMS simulation engines. These work directly with NeuroML and LEMS as their base descriptions of modeling entities and do not", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 191, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "73a4bfef-ef28-4bc1-82a8-1ad84534658a": {"__data__": {"id_": "73a4bfef-ef28-4bc1-82a8-1ad84534658a", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.34, para 12](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4cb19d67-4f07-4cbd-a02e-b1691c571a71", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.34, para 12](https://elifesciences.org/articles/95135)"}, "hash": "e113ba0a92653ff99ab65fd65384d0f775997b198ca807158a50c2058ac69e2e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135 34 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 94, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7fc415af-70a5-46d6-a692-0650e7f9b0e2": {"__data__": {"id_": "7fc415af-70a5-46d6-a692-0650e7f9b0e2", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.35, para 2](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7d7cc693-8725-41ed-ba9b-e4d514712876", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.35, para 2](https://elifesciences.org/articles/95135)"}, "hash": "b2af512635515dd684af14c9fed46aad1e951ae8512dff53dfac1326f85b600a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "```python\nsimulation_id = \"example-single-hindmarshrose1984cell-sim\"\nsimulation = LEMSSimulation(sim_id=simulation_id, duration=1.4e3, dt=0.0025, simulation_seed=123)\nsimulation.assign_simulation_target(net.id)\nsimulation.include_neuroml2_file(nml_file)\n```", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 257, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3ee94ee6-5a89-4484-a313-c73bcb0ba22b": {"__data__": {"id_": "3ee94ee6-5a89-4484-a313-c73bcb0ba22b", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.35, para 4](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9c963723-85be-4bee-a4db-d95154896774", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.35, para 4](https://elifesciences.org/articles/95135)"}, "hash": "f2f484604986e92a54cf26b408c401dc4dac079b9173f064635ebec696506dc7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "```python\nsimulation.create_output_file(\"output0\", \"%s.v.dat\" % simulation_id)\nsimulation.add_column_to_output_file(\"output0\", 'HRPop0[0]', 'HRPop0[0]/v')\n```", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 158, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7b94a5dc-105a-4c30-b4ae-f2fc83458ac9": {"__data__": {"id_": "7b94a5dc-105a-4c30-b4ae-f2fc83458ac9", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.35, para 6](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "79213664-f0e6-4975-8e10-5e0d9ade55e5", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.35, para 6](https://elifesciences.org/articles/95135)"}, "hash": "882dd8b0ee207bc1d350266676bf77b396ced9243a2451a64f24f5a4696544fc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "```python\nlems_simulation_file = simulation.save_to_file()\npynml.run_lems_with_jneuroml(lems_simulation_file, max_memory=\"2G\", nogui=True, plot=False)\n```", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 154, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "321e5683-2b84-49cf-82ca-bcb8c8e2d1ee": {"__data__": {"id_": "321e5683-2b84-49cf-82ca-bcb8c8e2d1ee", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.35, para 8](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c334ed77-547a-49be-b77f-59c018625476", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.35, para 8](https://elifesciences.org/articles/95135)"}, "hash": "a73272944422b10458cc75be8c402f48e923f0849226ac3f0fbd99eb2f715f7f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "```xml\n\n    \n    \n\n    \n    \n    \n    \n\n    \n\n     \n        \n            \n        \n    \n\n```", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 92, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c7c2cd07-9056-44ec-a0f6-6228103c8f6c": {"__data__": {"id_": "c7c2cd07-9056-44ec-a0f6-6228103c8f6c", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.35, para 9](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5cbc39ea-c74a-48f7-abe7-d6dffcc03474", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.35, para 9](https://elifesciences.org/articles/95135)"}, "hash": "4216556266793cb4d7c19d9857377868a56d93c8381e0ac9f0a63cf2657c3073", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Figure 15.** An example simulation of the HindmarshRose model description shown in **Figure 14** with the LEMS serialization shown at the bottom. The code used in this example is available here:", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 196, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e41582d6-61b5-40ea-9a09-7f654d4eb8b9": {"__data__": {"id_": "e41582d6-61b5-40ea-9a09-7f654d4eb8b9", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.35, para 10](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "743d7a04-b5f9-4916-8cc4-e246e866d8b1", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.35, para 10](https://elifesciences.org/articles/95135)"}, "hash": "0ccc5b58c4e338ea6e1fae0948d1647717a65c9675dc427c837fd18cd93e63a2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ".", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ca3521ca-186a-46e2-aac1-90c9164d247b": {"__data__": {"id_": "ca3521ca-186a-46e2-aac1-90c9164d247b", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.35, para 11](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f04361ad-b703-4917-9e8a-47ead35dfb89", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.35, para 11](https://elifesciences.org/articles/95135)"}, "hash": "95972f2734eaf2044445ee0a33b9ece3e5d26bfde0f44fb488d0d52b9599ac7a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "have their own specific formats. They are maintained by the NeuroML Editorial Board\u2014jLEMS, jNeuroML, and PyLEMS (*Figure 4*). jLEMS serves as the reference implementation for the LEMS language and as such it can simulate any model described in LEMS (not necessarily from neuroscience). When coupled with the LEMS definitions of NeuroML standard entity structure/dynamics, it can simulate most NeuroML models, though it does not currently support multi-compartmental neurons. jNeuroML bundles the NeuroML standard LEMS definitions, jLEMS, and other functionality into a single package for ease of installation/usage. There is also a pure Python implementation of a LEMS interpreter, PyLEMS, which can be used in a similar way to jLEMS. The pyNeuroML package encapsulates all of these tools to give easy access (at both command line and in Python) to all of their functionality (*Figure 6*).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 889, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "254e81de-094a-4ecd-ba92-5ce5642bba34": {"__data__": {"id_": "254e81de-094a-4ecd-ba92-5ce5642bba34", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.35, para 12](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "df445e54-bf2b-492a-9ef6-ea3c8b2a6017", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.35, para 12](https://elifesciences.org/articles/95135)"}, "hash": "dfdea5c62f926fbdb8d8d3681851a7b205db84164e243aeffc0d26bb1245115c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The second category consists of other simulators which support NeuroML natively. The EDEN simulator is an independently developed tool that was designed from its inception to read NeuroML and LEMS models for efficient, parallel simulation (*Panagiotou et al., 2022*).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 267, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "641e73f5-45f8-4d38-898f-4554af488789": {"__data__": {"id_": "641e73f5-45f8-4d38-898f-4554af488789", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.35, para 13](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3cb142ea-b235-414e-90ca-3acdeea6bb8a", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.35, para 13](https://elifesciences.org/articles/95135)"}, "hash": "eeda61e4822bede97c889942dfd8d8eb3bb992a50a9916fc57b9c91aff1db01f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The third category involves simulators which have their own internal formats and include methods to translate NeuroMLv2/LEMS models to their own formats. Examples include NetPyNE (*Dura-Bernal et al., 2019*), MOOSE (*Ray and Bhalla, 2008*), and N2A (*Rothganger et al., 2014*).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 277, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d2d8ef7d-1ca7-4776-b1d6-c084d0ceb046": {"__data__": {"id_": "d2d8ef7d-1ca7-4776-b1d6-c084d0ceb046", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.35, para 14](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f2dcd621-17e1-46bd-8307-96daefd0b3c4", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.35, para 14](https://elifesciences.org/articles/95135)"}, "hash": "7b82bf72dc8aa27d9b37fb239e33c4e2f3084b20359c70f8191350178329542e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The fourth category comprises tools for which the NeuroML tools generate simulator specific scripts. The simulation engines then execute these scripts, similar to how they would execute handwritten", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 197, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b92996f6-175c-4a62-b87b-d75e4fb75414": {"__data__": {"id_": "b92996f6-175c-4a62-b87b-d75e4fb75414", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.35, para 15](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "67f73029-39a6-4953-b979-48ea5b5f4b65", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.35, para 15](https://elifesciences.org/articles/95135)"}, "hash": "53c5751cded361e946a3ea0874fe66390353c84b86b1edf44f4157c0b0ec6f6c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135 35 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 94, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cd463ec4-646f-498c-8094-dd1a4a40d510": {"__data__": {"id_": "cd463ec4-646f-498c-8094-dd1a4a40d510", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 1](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0a193f4c-3f07-47be-a0a4-23e339ad3f8e", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 1](https://elifesciences.org/articles/95135)"}, "hash": "aa8187e529081c35c75f1c27aab766875a8a6f6980573fcfd086bb0b24c64419", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "user scripts. These include NEURON (*Hines and Carnevale, 1997*) for which the NeuroML tools generate scripts in Python and the simulator\u2019s hoc and NMODL formats and the Brian simulator (*Stimberg et al., 2019*) which uses Python scripts.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 238, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b6417a7c-5c65-4ce9-a407-b18472d6c9bb": {"__data__": {"id_": "b6417a7c-5c65-4ce9-a407-b18472d6c9bb", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 2](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e6eb45a3-e78e-4a3d-9225-f4afde79cc00", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 2](https://elifesciences.org/articles/95135)"}, "hash": "55ab65e95154c7a94b5179b6bafa7f409d71e00cc2dff5129bd1e2e024c47a14", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The final category consists of export options to standardized formats in neuroscience and the wider computational biology field, which enable interaction with simulators and applications supporting those formats. These include the PyNN package (*Davison et al., 2008*), which can be run in either NEURON, NEST (*Gewaltig and Diesmann, 2007*) or Brian, the SONATA data format (*Dai et al., 2020*) and the SBML standard (*Hucka et al., 2003*) (see Reusing NeuroML models for more details).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 487, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f6b5ee7d-c671-46be-abac-28fa2816949b": {"__data__": {"id_": "f6b5ee7d-c671-46be-abac-28fa2816949b", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 3](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "954f4dae-80e8-4c8f-90bd-46aa0904c0f7", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 3](https://elifesciences.org/articles/95135)"}, "hash": "bd8b92bc52a76ce1f6a669c92e9ee1fb62c3a73911773e24b40db18753e35f19", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Having multiple strategies in place for supporting NeuroML gives more freedom to simulator developers to choose how much they wish to be involved with implementing and supporting NeuroML functionality in their applications, while maximizing the options available for end users.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 277, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2a47ab50-bd0c-471c-9501-13441662449e": {"__data__": {"id_": "2a47ab50-bd0c-471c-9501-13441662449e", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 4](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d986fce4-2ba5-4ee5-a62b-b7555935d43d", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 4](https://elifesciences.org/articles/95135)"}, "hash": "384886f2dcabc00f28585d62da9befc6198a26d92b519a8134760ea3f00946ee", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The primary tool for simulating NeuroML/LEMS models via different engines is jNeuroML, which is included in pyNeuroML. jNeuroML supports all simulator engine categories (*Figure 5*). It includes jLEMS for simulation of LEMS and single compartmental NeuroML models. It can also pass simulations to the EDEN simulator (*Panagiotou et al., 2022*) for direct simulation. Using the `org.neuroml.export` library (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 407, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "45bc8070-2018-449d-9fbe-f2af6c1210af": {"__data__": {"id_": "45bc8070-2018-449d-9fbe-f2af6c1210af", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 5](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ac21f0c7-2201-4b6a-aee6-a246e3dff45b", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 5](https://elifesciences.org/articles/95135)"}, "hash": "184311b2fd24943a89d3a5932275ae47a15a2f802189cfb2cc673cd7bc9e5e16", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "), jNeuroML can also generate import scripts for simulators (e.g. NetPyNE *Dura-Bernal et al., 2019*) or convert NeuroML/LEMS models to simulator specific formats (e.g. NEURON *Hines and Carnevale, 1997*). Supporting a new simulation engine that requires translation of NeuroML/LEMS into another format can be done by adding a new \u2018writer\u2019 to the `org.neuroml.export` library. Finally, jNeuroML also includes the `org.neuroml.import` (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 435, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d97bccbd-1a88-4906-9e22-435f1340e4a0": {"__data__": {"id_": "d97bccbd-1a88-4906-9e22-435f1340e4a0", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 6](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9b97b778-777c-498f-8e75-f70136b5037a", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 6](https://elifesciences.org/articles/95135)"}, "hash": "e8accdefa0e3e263546512e5d0e92f2d34765fec10f4864a5fdb10ba479fc739", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ") library that converts from other formats (e.g. SBML *Hucka et al., 2003*) to LEMS for combination with NeuroML models.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 120, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "65ae0f70-aab3-4f35-ac4a-c617acb14634": {"__data__": {"id_": "65ae0f70-aab3-4f35-ac4a-c617acb14634", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 7](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "621825c8-9623-4b31-8ed3-9bd06607a413", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 7](https://elifesciences.org/articles/95135)"}, "hash": "f41b96fe578e5a935aad463b1a4bae76460dafa5e5e45b95f3ee4039c176617f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "It is important to note though that not all NeuroML models can be exported to/are supported by each of these target simulators (*Table 7*). This depends on the capabilities of the simulator in question (whether it supports networks, or morphologically detailed cells) and pyNeuroML/jNeuroML will provide feedback if a feature of the model is not supported in a chosen environment.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 380, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8b4bd017-1a2e-4624-a249-0976dcf19742": {"__data__": {"id_": "8b4bd017-1a2e-4624-a249-0976dcf19742", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 8](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "27540618-e422-43d2-8ebb-5cd45c581614", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 8](https://elifesciences.org/articles/95135)"}, "hash": "9c54ef7cf5120b1b26917f4de13fb87653390b96ddbdb0b88381178de9881bb7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "All NeuroML and LEMS software packages are made available under FOSS licenses. The source code for all NeuroML packages and the standard can be obtained from the NeuroML GitHub organization (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 191, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3f052940-1a42-4e1b-bdfc-8608499ba2c8": {"__data__": {"id_": "3f052940-1a42-4e1b-bdfc-8608499ba2c8", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 10](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9aade4ee-132e-4f80-8537-6f0c1f66261a", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 10](https://elifesciences.org/articles/95135)"}, "hash": "a25fed7ce7de4ac59909c28b379b49a83b92bdc6003db38cbc97c0715dbe37ed", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ") was developed in collaboration with the NeuralEnsemble initiative (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 69, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1cff4683-b483-490c-a830-00487df43a03": {"__data__": {"id_": "1cff4683-b483-490c-a830-00487df43a03", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 11](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "639d1b38-b1f1-4cd8-a64d-d752a3657cd3", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 11](https://elifesciences.org/articles/95135)"}, "hash": "d54eee24be8cadcbe7b7ddfc8304ec5be992e184ff91962b8b15173c59c74fc9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "), which also maintains other commonly used Python packages such as PyNN (*Davison et al., 2008*), Neo (*Garcia et al., 2014*) and Elephant (*Denker, 2018*). LEMS packages are available from the LEMS GitHub organization (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 221, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3780759c-a0da-43cb-a991-c21c20b49901": {"__data__": {"id_": "3780759c-a0da-43cb-a991-c21c20b49901", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 12](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "696196fe-e12e-4925-abd3-c0fe28bce8b7", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 12](https://elifesciences.org/articles/95135)"}, "hash": "0b0049acda0527198e17b8e541ced09dea7054a429ebc050ba81e76dfc288434", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ").", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "857ada31-80ca-4168-bf7b-7ceb60007068": {"__data__": {"id_": "857ada31-80ca-4168-bf7b-7ceb60007068", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 13](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9f8b78a7-4f39-4812-9d63-4ac0352ded7e", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 13](https://elifesciences.org/articles/95135)"}, "hash": "460911fe59c92910da949d0a00cf63693e078b5f169e169b0b3d96b412519100", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "To ensure replication and reproduction of studies, it is important to note the exact versions of software used in studies. For NeuroML and LEMS packages, archives of each release along with citations are published on Zenodo (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 225, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8348c21b-fd96-4542-9d9b-6f4fa50f25d0": {"__data__": {"id_": "8348c21b-fd96-4542-9d9b-6f4fa50f25d0", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 14](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ceb0d107-3f02-4258-97f0-8039c10ed9da", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 14](https://elifesciences.org/articles/95135)"}, "hash": "36f21a45ecc88d2d92398f4a1eabed106089dd73e6c7b2b6f628d1cbb24963ec", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ") to enable researchers to cite them in their work (*Gleeson, 2021; Gleeson, 2024a; Gleeson et al., 2019b; Gleeson, 2024b; Sinha, 2024*).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 137, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6921ede5-9d43-45f4-9c79-d9460cda149b": {"__data__": {"id_": "6921ede5-9d43-45f4-9c79-d9460cda149b", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 15](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6402b2cd-3334-4099-a2bd-c0cbbb543d6f", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 15](https://elifesciences.org/articles/95135)"}, "hash": "5e1828fb25c54cc8969f0820863a5769ccff365ef669f8e10a1e3c00e4e4c33d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Documentation", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 16, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c279ce04-5d4f-4f18-92f7-c5cd185ab4dc": {"__data__": {"id_": "c279ce04-5d4f-4f18-92f7-c5cd185ab4dc", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 16](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "33cd3141-6d72-4e18-89be-fd96d51c04ad", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 16](https://elifesciences.org/articles/95135)"}, "hash": "02a83531060b74f2777372ae8b641a4b75767997d6d4acf2321dd988ef9dd7dc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "A standard and its accompanying software ecosystem must be supported by comprehensive documentation if it is to be of use to the research community. The primary NeuroML documentation for users that accompanies this paper has been consolidated into a JupyterBook (*Executable Books Community, 2020*) at", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 301, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5c5c2a6d-e805-40fb-9012-8ce5917300d4": {"__data__": {"id_": "5c5c2a6d-e805-40fb-9012-8ce5917300d4", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 17](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b12c1db9-d41f-4c68-b178-2f3bdf0de3d6", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 17](https://elifesciences.org/articles/95135)"}, "hash": "cbf6d1515da2f6f68aceb73bf349499d4eff0f5b296973f1e2e384720e58588e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ". This includes explanations of NeuroML and computational modeling concepts, interactive tutorials with varying levels of complexity, information about tools and what functions they provide to support different stages of the model life cycle. The JupyterBook framework supports \u2018executable\u2019 documentation through the inclusion of interactive Jupyter notebooks which may be run in the users\u2019 web browser on free services such as OSBv2, Binder.org (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 447, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0ac8ff4c-6c43-4a04-9ed3-ceb32175c61d": {"__data__": {"id_": "0ac8ff4c-6c43-4a04-9ed3-ceb32175c61d", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 19](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6529330c-7feb-4bc6-8f00-446ff4d2e442", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 19](https://elifesciences.org/articles/95135)"}, "hash": "6b10f3ec0b4479d2512a96e6b3bbd65abd8fa20e8916f9a2f4e23e6b6e94f187", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "). Finally, the machine readable nature of the schema and LEMS also enables the automated generation of human readable documentation for the standard and low level APIs (*Figure 16*) along with their examples (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 210, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4232625b-1bdf-4f47-ba72-c111d3a136af": {"__data__": {"id_": "4232625b-1bdf-4f47-ba72-c111d3a136af", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 20](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d6338a24-b818-43ce-bc0c-3e5deffd65e5", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 20](https://elifesciences.org/articles/95135)"}, "hash": "70b3475ddf3748f1f23fdf5caf76dc7ba9be27878911cc82d61526d96d7338ab", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "). In addition, the individual NeuroML software packages each have their own individual documentation (e.g. pyNeuroML (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 119, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2f22c308-2778-440b-9d5d-9018a0725e4f": {"__data__": {"id_": "2f22c308-2778-440b-9d5d-9018a0725e4f", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 22](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d7c042cc-c499-41a8-b4e0-cb8b718dd78a", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 22](https://elifesciences.org/articles/95135)"}, "hash": "9b630c404ffdd5f8054066f746c4ea56214f3620143703d56b65f3c7f4e8b8b0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ")).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 3, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4772a94a-3d16-4a10-8c29-a79764f4a7a1": {"__data__": {"id_": "4772a94a-3d16-4a10-8c29-a79764f4a7a1", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 23](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e957e0c8-e2c6-4262-84fa-de0e383ff2be", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 23](https://elifesciences.org/articles/95135)"}, "hash": "8c032ef96832c49056aee085b924ee11dfae7e2194c4a641c27392c45ea0fcea", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "As with the rest of the NeuroML ecosystem, the documentation is hosted on GitHub (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 82, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "dfc1b12c-7f57-4633-b2c0-e849b0595f4a": {"__data__": {"id_": "dfc1b12c-7f57-4633-b2c0-e849b0595f4a", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 24](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "840c6d04-6505-4d4e-86c8-b22a83136b78", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 24](https://elifesciences.org/articles/95135)"}, "hash": "33d4404f6b9406f181bb91ed2c764e9a1ea144b473d604d24ddf4465b9ee5735", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "), licensed under a FOSS license, and community contributions", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 61, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1c8c351e-f520-4f16-b44d-ba901fbd82eb": {"__data__": {"id_": "1c8c351e-f520-4f16-b44d-ba901fbd82eb", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 25](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d297ec88-8b43-4f6b-9f68-3431d6b7b109", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.36, para 25](https://elifesciences.org/articles/95135)"}, "hash": "0b45a1b6286e1fa165c859f16342458e7f233799fc0d800e6480085cc3454457", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135 36 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 94, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b58850f4-6cc8-435c-ac85-eb5287806b04": {"__data__": {"id_": "b58850f4-6cc8-435c-ac85-eb5287806b04", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.37, para 1](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "17ca61af-02c2-4860-a197-fefa87f55c0f", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.37, para 1](https://elifesciences.org/articles/95135)"}, "hash": "4eab22d34959ca58014370d93fbbcfd4aef00987baad82482668a8565cfebd9d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# hindmarshRose1984Cell", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 23, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2b4f1a8e-7f4c-4014-a422-098891a81272": {"__data__": {"id_": "2b4f1a8e-7f4c-4014-a422-098891a81272", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.37, para 3](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5369d31e-241f-400e-8be7-6a4db68425e3", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.37, para 3](https://elifesciences.org/articles/95135)"}, "hash": "c6c733b6c7c2e73257b773abf6b3f242f4ba3cb9cb17204d433b08e99d07ab92", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "*The Hindmarsh Rose model is a simplified point cell model which captures complex firing patterns of single neurons, such as periodic and chaotic bursting. It has a fast spiking subsystem, which is a generalization of the FitzHugh-Nagumo system, coupled to a slower subsystem which allows the model to fire bursts. The dynamical variables x, y, z correspond to the membrane potential, a recovery variable, and a slower adaptation current, respectively. See Hindmarsh J. L., and Rose R. M. ( 1984 ) A model of neuronal bursting using three coupled first order differential equations. Proc. R. Soc. London, Ser. B 221:87\u2013102.*", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 624, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5328c23e-e844-4c94-aa44-6c227a22b689": {"__data__": {"id_": "5328c23e-e844-4c94-aa44-6c227a22b689", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.37, para 4](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e8f1f2e2-aeb9-4a27-935d-3b4df4154edd", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.37, para 4](https://elifesciences.org/articles/95135)"}, "hash": "bb0928a9a296fb4c9ea56ceff2ab7b60e6e4b53a0ebce5b45cfb629d37ba7721", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Parameters|Constants|Exposures|Event Ports|Attachments|Dynamics|\n|-|-|-|-|-|-|\n|Schema|Usage: Python|||||", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 106, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ed1815e9-1871-49be-b3ef-84113dc61053": {"__data__": {"id_": "ed1815e9-1871-49be-b3ef-84113dc61053", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.37, para 6](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "01532d46-e886-404a-9fe9-bcdbdd8cd9ba", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.37, para 6](https://elifesciences.org/articles/95135)"}, "hash": "b06690ae805c405e61788a629df503950376b31a4d06ce29fed1bcb6a7dd6468", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* **v**: voltage (exposed as **v**)\n* **y**: Dimensionless (exposed as **y**)\n* **z**: Dimensionless (exposed as **z**)\n* **spiking**: Dimensionless (exposed as **spiking**)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 173, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d4b66f18-d6b1-4d99-a9ca-30af84777ec6": {"__data__": {"id_": "d4b66f18-d6b1-4d99-a9ca-30af84777ec6", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.37, para 10](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9f04efbc-03f0-4c39-bc65-bb3f2fb3bb44", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.37, para 10](https://elifesciences.org/articles/95135)"}, "hash": "abb8d3df831f6382ce232e76e902f9c22a6aaed50130c388e546d0cb04b061bb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* IF v > 0 AND spiking < 0.5 THEN\n  * spiking = 1\n  * EVENT OUT on port: **spike**\n* IF v < 0 THEN\n  * spiking = 0", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 114, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f160ac11-ee94-4bb9-b461-e84ba5823b10": {"__data__": {"id_": "f160ac11-ee94-4bb9-b461-e84ba5823b10", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.37, para 12](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "751b971a-96f4-472a-a8db-2639a343cfad", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.37, para 12](https://elifesciences.org/articles/95135)"}, "hash": "805bbc87e1838259a8a8bf4d1000198d77be93abf8a38e7cd2967af47acdd677", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* **iSyn** = synapses\\[\\*]->i(reduce method: add) (exposed as **iSyn**)\n* **x** = v / v\\_scaling (exposed as **x**)\n* **phi** = y - a \\* x^3 + b \\* x^2 (exposed as **phi**)\n* **chi** = c - d \\* x^2 - y (exposed as **chi**)\n* **rho** = s \\* ( x - x1 ) - z (exposed as **rho**)\n* **iMemb** = (C \\* (v\\_scaling \\* (phi - z) / MSEC)) + iSyn (exposed as **iMemb**)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 359, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3253e43e-7014-4f4a-8e2c-ca22c190f428": {"__data__": {"id_": "3253e43e-7014-4f4a-8e2c-ca22c190f428", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.37, para 14](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "115efa6a-4534-4c7f-af0c-411697619ab3", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.37, para 14](https://elifesciences.org/articles/95135)"}, "hash": "bd9c64019ebc9a1657189b590ee24eaf959ad47455f02aac80f03961c155e836", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* d **v** /dt = iMemb/C\n* d **y** /dt = chi / MSEC\n* d **z** /dt = r \\* rho / MSEC", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 82, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "71b22aa0-a394-40c7-9cfb-52a1729d6205": {"__data__": {"id_": "71b22aa0-a394-40c7-9cfb-52a1729d6205", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.37, para 15](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "10871712-abd4-4bf2-b6d5-164fed011703", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.37, para 15](https://elifesciences.org/articles/95135)"}, "hash": "b1d1a06387929409858c11d8ae45e654a9dde941fb70c08b41b3e7c261637abd", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Previous|Next|\n|-|-|\n||", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 24, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2b49f4b3-8e4e-4c05-9b8c-9ee181dfd5a4": {"__data__": {"id_": "2b49f4b3-8e4e-4c05-9b8c-9ee181dfd5a4", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.37, para 16](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "158fd732-b4a3-4062-a21e-0f8627dae535", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.37, para 16](https://elifesciences.org/articles/95135)"}, "hash": "3ed1897f1907ca80c8b800d17b1a9b571e1e38e131567c1ad0661926bce95881", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Figure 16.** Documentation for the `HindmarshRose1984Cell` NeuroMLv2 `ComponentType` generated from the XSD schema and LEMS definitions on the NeuroML documentation website showing its dynamics (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 197, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5fb25d39-de45-4f41-b4ac-d816c4ccfd87": {"__data__": {"id_": "5fb25d39-de45-4f41-b4ac-d816c4ccfd87", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.37, para 17](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4132ea58-579c-4160-9f83-2449a932bcf4", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.37, para 17](https://elifesciences.org/articles/95135)"}, "hash": "86ccd5bce8cbd6e9ef812a127c84bf43706e58ef842c6949e0bc46e3e2413002", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "). More information about the ComponentType can be obtained from the tabs provided.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 83, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b2ca57c5-c998-4b6e-9cfa-f08c994f2c8a": {"__data__": {"id_": "b2ca57c5-c998-4b6e-9cfa-f08c994f2c8a", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.37, para 18](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "24b17800-0359-4c6e-a412-fe032bd39716", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.37, para 18](https://elifesciences.org/articles/95135)"}, "hash": "08e188f510ee38071d123a9efb751a2727ec6ee1133e1e04a473d8717b5df242", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135\n37 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 94, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "33c1dad7-3ded-4455-8ada-997ef583363e": {"__data__": {"id_": "33c1dad7-3ded-4455-8ada-997ef583363e", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.38, para 1](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "375a3aed-87d0-4bb1-86f3-d1d0003be8d6", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.38, para 1](https://elifesciences.org/articles/95135)"}, "hash": "c6eae30c3b553f1d86007ef04c0fd9bd1c8b851f7015fa585cb5c06fecd15f21", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "to it are welcomed. A PDF version of the documentation can also be downloaded for offline use (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 95, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9c072783-5a40-4014-8bfd-23fb75c3697d": {"__data__": {"id_": "9c072783-5a40-4014-8bfd-23fb75c3697d", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.38, para 2](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "90cf4ea6-c5b3-4e3d-bedc-326062f6ee9a", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.38, para 2](https://elifesciences.org/articles/95135)"}, "hash": "187726658cdc8c8a3d01a34621562753cda50b3b59d2df0ad67e3351c8f37fd1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ").", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "93ef824c-034c-459c-8922-ab2c55b2cdd2": {"__data__": {"id_": "93ef824c-034c-459c-8922-ab2c55b2cdd2", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.38, para 3](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4e1cc6bc-9690-487f-aad6-be763a256704", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.38, para 3](https://elifesciences.org/articles/95135)"}, "hash": "7c3608344a3a6e2b2335d7bcc57ec955fd2b2bb57f7c43455c2a517dae456f07", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Maintenance of the Schema and core software", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 46, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b45f865d-dfd0-48e6-84c4-a6b71aefd0b8": {"__data__": {"id_": "b45f865d-dfd0-48e6-84c4-a6b71aefd0b8", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.38, para 6](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "640de089-ee87-4eb1-88e1-71d5189d5f63", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.38, para 6](https://elifesciences.org/articles/95135)"}, "hash": "2927442e7c9b83d1c6550c4204d3f22d646d0fbe6ee382736cc4a64a367c12c3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ") oversee the standard, the core tools, and the initiative. The Scientific Committee sets the scientific focus of the NeuroML initiative. It ensures that the standard represents the state of the art\u2014that it can encapsulate the latest knowledge in neuronal anatomy and physiology in their corresponding model components. The Scientific Committee also defines the governance structure of the initiative and works with the wider scientific community to gather feedback on NeuroML and promote its use. The Editorial Board manages the day-to-day development and maintenance of LEMS, the NeuroML schema, the core software tools, and critical resources such as the documentation. The Editorial Board works with simulator developers in the extended ecosystem to help make tools NeuroML compliant by testing reference implementations and answering technical queries about NeuroML and the core software tools.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 899, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0b317df8-507f-4ce0-bfb8-76a4612e4ab7": {"__data__": {"id_": "0b317df8-507f-4ce0-bfb8-76a4612e4ab7", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.38, para 7](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a0b52c6a-3709-4918-9145-0b64f68c7bf3", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.38, para 7](https://elifesciences.org/articles/95135)"}, "hash": "7dadd7a5f7ecb8855deeee405e78ae7f89d024f57a50477f2045e6bac9b73e61", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Acknowledgements", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 19, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1dfbf437-027e-4dc6-800e-37fe565574b9": {"__data__": {"id_": "1dfbf437-027e-4dc6-800e-37fe565574b9", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.38, para 8](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "21064530-e59e-4d22-b822-f1ca28d86994", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.38, para 8](https://elifesciences.org/articles/95135)"}, "hash": "3022b2a9f3b0ae66d0cdfe0926726147cf6b0b7ee39ca8bced27006e0e7dea5b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We thank all the members of the NeuroML Community who have contributed to the development of the standard over the years, have added support for the language to their applications, or who have converted published models to NeuroML. We would particularly like to thank the following for contributions to the NeuroML Scientific Committee: Upi Bhalla, Avrama Blackwell, Hugo Cornells, Robert McDougal, Lyle Graham, Cengiz Gunay, and Michael Hines. The following have also contributed to developments related to the named tools/simulators/resources: EDEN - Mario Negrello and Christos Strydis, SONATA - Anton Arkhipov and Kael Dai, MOOSE - Subhasis Ray, NeuroML-DB - Justas Birgiolas, NeuroMorpho.Org - Giorgio Ascoli, N2A - Fred Rothganger, pyLEMS - Gautham Ganapathy, MDF - Manifest Chakalov, libNeuroML and NeuroTune - Mike Vella, Open Source Brain - Matt Earnshaw, Adrian Quintana and Eugenio Piasini, SciUnit/NeuronUnit - Richard C Gerkin, Brian - Marcel Stimberg and Dominik Krzemi\u0144ski, Arbor - Nora Abi Akar, Thorsten Hater and Brent Huisman, BluePyOpt - Jaquier Aur\u00e9lien Tristan and Werner van Geit, C++/MATLAB APIs - Jonathan Cooper. We thank Rokas Stanislavos, Andr\u00e1s Ecker, Jessica Dafflon, Ronaldo Nunes, Anuja Negi, and Shayan Shafquat for their work converting models to NeuroML format as part of the Google Summer of Code program. We also thank Diccon Coyle for feedback on the manuscript.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1400, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "61e196fd-e885-4254-b1be-342aa5343883": {"__data__": {"id_": "61e196fd-e885-4254-b1be-342aa5343883", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.38, para 9](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "eddbf848-5160-49e4-bfee-f9d6b3609f8b", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.38, para 9](https://elifesciences.org/articles/95135)"}, "hash": "c4d3b4acc2a621a36ffa31f2b4284fc482f478a5f8fbfb628c21e352fa94d3a2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Additional information", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 24, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6734787f-e785-4965-93fd-e38fda307d94": {"__data__": {"id_": "6734787f-e785-4965-93fd-e38fda307d94", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.38, para 10](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "082b7521-3717-4b7b-9636-2410fbabdf77", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.38, para 10](https://elifesciences.org/articles/95135)"}, "hash": "b9c8c0e49e402ced4bc89f6f95539281912dae68fd463ec24d391d490b5c904e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Competing interests", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 23, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "dc0100d8-2227-4e27-804f-6d335401de7e": {"__data__": {"id_": "dc0100d8-2227-4e27-804f-6d335401de7e", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.38, para 11](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c74d9d32-5503-4fa4-89eb-99ddb775e7bc", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.38, para 11](https://elifesciences.org/articles/95135)"}, "hash": "d926210cfc7d532242caec1d17e340ba6b1f82803b9c285e83302b3ff62d7666", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Matteo Cantarelli: MetaCell Ltd. was contracted by UCL to develop some of the NeuroML support on the Open Source Brain platform; MC has a financial interest in MetaCell Ltd. Robert C Cannon: Employee of Opus2 International Ltd. The other authors declare that no competing interests exist.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 288, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cde4e8b0-2cce-4a67-9ad4-930b06ec1efe": {"__data__": {"id_": "cde4e8b0-2cce-4a67-9ad4-930b06ec1efe", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.38, para 12](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5b89e583-ae5f-4ca5-b3e2-9136365e7055", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.38, para 12](https://elifesciences.org/articles/95135)"}, "hash": "14035e6e9c18178ec5efeaf915b080a95baa9e52941dfd7b5b59563dd2622959", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Funding", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 11, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c337f536-c736-4f0f-bc5e-e00051d0b690": {"__data__": {"id_": "c337f536-c736-4f0f-bc5e-e00051d0b690", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.38, para 13](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "69fd13df-6179-4022-b92b-eb810e141294", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.38, para 13](https://elifesciences.org/articles/95135)"}, "hash": "25dc62db1f412c2be3a1507bdafec0800bb3309b44c7a2d4f4d0f8371c0d558d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Funder|Grant reference number|Author|\n|-|-|-|\n|Wellcome Trust|10.35802/101445|Padraig GleesonRobin Angus Silver|\n|Wellcome Trust|10.35802/212941|Padraig GleesonRobin Angus Silver|\n|Wellcome Trust|10.35802/203048|Robin Angus Silver|\n|Wellcome Trust|10.35802/224499|Robin Angus Silver|\n|Kavli Foundation|LS-2022-GR-40-2648|Padraig Gleeson|", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 338, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "83dbb1fb-1f61-486d-a7fd-b05adb0d0898": {"__data__": {"id_": "83dbb1fb-1f61-486d-a7fd-b05adb0d0898", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.38, para 14](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a2b25071-2ddc-4d39-9119-d8a6958fd34a", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.38, para 14](https://elifesciences.org/articles/95135)"}, "hash": "0f18c1dc34a930fc6621fcdb1160ad2d10f395c284f1f3a15589230158f21cd5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135 38 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 94, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2c03862e-d86a-4dd7-b5a8-ab84ffb1a78f": {"__data__": {"id_": "2c03862e-d86a-4dd7-b5a8-ab84ffb1a78f", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.39, para 1](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "dbb9b306-697e-41d6-bd1f-4f70a66cf330", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.39, para 1](https://elifesciences.org/articles/95135)"}, "hash": "9055fd4b2649297cd78c767d11134e7774622a9ebe951000f8c3def54f3adc74", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Funder|Grant reference number|Author|\n|-|-|-|\n|Engineering and Physical Sciences Research Council|EP/X011151/1|Padraig Gleeson|\n|National Institutes of Health|MH081905|Sharon Crook|\n|National Institutes of Health|EB014640|Sharon Crook|\n|National Institutes of Health|MH106674|Sharon Crook|\n|National Institutes of Health|U24EB028998|Salvador Dura-Bernal|\n|New York State Department of Health - Wadsworth Center|DOH01-C38328GG|Salvador Dura-Bernal|\n|HORIZON EUROPE Framework Programme|SEPTON (Gr. Agr. No. 101094901)|Sotirios Panagiotou|", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 537, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "034a10a3-1c8c-4313-8bb1-12578668a62e": {"__data__": {"id_": "034a10a3-1c8c-4313-8bb1-12578668a62e", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.39, para 2](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6ffe8322-d6c5-497b-9add-bea0982966df", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.39, para 2](https://elifesciences.org/articles/95135)"}, "hash": "6175da4222e02cb0b97b59f32e80024e3851b45dd7c18c6fa46f27e33716fb80", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. For the purpose of Open Access, the authors have applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 290, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6f2f5d77-36a5-46a7-8e4c-adba2b195909": {"__data__": {"id_": "6f2f5d77-36a5-46a7-8e4c-adba2b195909", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.39, para 3](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "40526257-1a6b-4989-89da-50626cf60bad", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.39, para 3](https://elifesciences.org/articles/95135)"}, "hash": "e9ac76c770d1414eb6c72b976c000e530878afc943a74a1fbc6c942ea992eb1b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Author contributions", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 23, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ae9e334c-f996-4a00-8ece-08a33d42105d": {"__data__": {"id_": "ae9e334c-f996-4a00-8ece-08a33d42105d", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.39, para 4](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "019d2a6f-a5fd-407a-af1b-c4a7adb9609e", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.39, para 4](https://elifesciences.org/articles/95135)"}, "hash": "996b3bfbc90c98916b196bebd2a4ddfb584e95703c58d1ab59dcb68dc32950df", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Ankur Sinha**, Conceptualization, Resources, Data curation, Software, Formal analysis, Validation, Investigation, Visualization, Methodology, Writing \u2013 original draft, Project administration, Writing \u2013 review and editing; **Padraig Gleeson**, Conceptualization, Resources, Data curation, Software, Formal analysis, Supervision, Funding acquisition, Validation, Investigation, Visualization, Methodology, Writing \u2013 original draft, Project administration, Writing \u2013 review and editing; **B\u00f3ris Marin**, Conceptualization, Resources, Software, Validation, Investigation, Methodology, Writing \u2013 review and editing; **Salvador Dura-Bernal**, Conceptualization, Resources, Software, Funding acquisition, Investigation, Visualization, Methodology, Writing \u2013 review and editing; **Sotirios Panagiotou**, Resources, Software, Validation, Investigation, Methodology, Writing \u2013 review and editing; **Sharon Crook**, Conceptualization, Resources, Software, Supervision, Funding acquisition, Validation, Investigation, Methodology, Writing \u2013 review and editing; **Matteo Cantarelli**, Conceptualization, Resources, Software, Validation, Investigation, Visualization, Methodology, Writing \u2013 review and editing; **Robert C Cannon**, Conceptualization, Resources, Software, Investigation, Methodology; **Andrew P Davison**, Software, Investigation, Methodology, Writing \u2013 review and editing; **Harsha Gurnani**, Data curation, Software, Validation, Investigation, Methodology; **Robin Angus Silver**, Conceptualization, Formal analysis, Supervision, Funding acquisition, Investigation, Methodology, Writing \u2013 original draft, Project administration, Writing \u2013 review and editing", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1663, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "52afb5ad-7fa5-49e3-aefa-ff0479e2f0f9": {"__data__": {"id_": "52afb5ad-7fa5-49e3-aefa-ff0479e2f0f9", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.39, para 5](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c12d9fa0-29de-4126-a8fc-2e2fe67dfa3e", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.39, para 5](https://elifesciences.org/articles/95135)"}, "hash": "5cbdca5d1e49ef77204eb4deb97643b61c3ae1600ecde5ab23e59056e646e9cc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Author ORCIDs", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 16, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "56e5a2c9-fd9d-44df-b335-83375fb83f24": {"__data__": {"id_": "56e5a2c9-fd9d-44df-b335-83375fb83f24", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.39, para 11](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "44767aad-6464-497e-ba66-f07ce6f84e16", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.39, para 11](https://elifesciences.org/articles/95135)"}, "hash": "b64892009406647f0df436a24b42c0985f36e299377468eb179bab8485c27a7b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Peer review material", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 23, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1f386aca-72e6-41a3-af31-57897982332e": {"__data__": {"id_": "1f386aca-72e6-41a3-af31-57897982332e", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.39, para 12](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d17cbda9-bb6a-4040-b95f-09b9e0268579", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.39, para 12](https://elifesciences.org/articles/95135)"}, "hash": "a250c67ba18e719425bd243b034457c364490bd0928ab0e97ab3b500552d6fdb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Reviewer #1 (Public review):", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 28, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "358b6869-5e7b-4087-bf67-e55b86dfc3fa": {"__data__": {"id_": "358b6869-5e7b-4087-bf67-e55b86dfc3fa", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.39, para 13](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5d34950f-6e39-405f-a56f-70443e812a33", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.39, para 13](https://elifesciences.org/articles/95135)"}, "hash": "e675e22f8d23432ac69af355f02381217860b3924f840094cd934d58af0619bb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Reviewer #2 (Public review):", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 28, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "07a7dd86-1b18-409d-9971-18cf97da7cfa": {"__data__": {"id_": "07a7dd86-1b18-409d-9971-18cf97da7cfa", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.39, para 15](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a644f532-0455-4041-b333-e544340672a5", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.39, para 15](https://elifesciences.org/articles/95135)"}, "hash": "96159f1ce0795cd242c2dc8ff6165f5d328884525feeb038b91b8d8342e9f395", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Additional files", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 18, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "aaa15f4d-a287-44b5-b2b2-afa13c0e097f": {"__data__": {"id_": "aaa15f4d-a287-44b5-b2b2-afa13c0e097f", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.39, para 16](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8fbd6ebd-2515-4627-a5f2-ef3908441025", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.39, para 16](https://elifesciences.org/articles/95135)"}, "hash": "163837e16ed211d91c0789d52f61aca30b641886768bc597eac35055c40e2c67", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Supplementary files", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 23, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8be7ae6d-53f0-4404-8263-2b0d121aa007": {"__data__": {"id_": "8be7ae6d-53f0-4404-8263-2b0d121aa007", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.39, para 18](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ec07ac2e-2491-420a-9654-39319f9b9fe9", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.39, para 18](https://elifesciences.org/articles/95135)"}, "hash": "6e62b19cc46d62d6908fd65a723be81ccdba8a63c87651735e902da4324ee2d0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135 39 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 94, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "76059186-08c6-4051-92a5-b3dddbacdf97": {"__data__": {"id_": "76059186-08c6-4051-92a5-b3dddbacdf97", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.40, para 1](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6b775c02-60d6-47ae-8e07-7a70a87af8af", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.40, para 1](https://elifesciences.org/articles/95135)"}, "hash": "081351f416239304b420be71b6714e891c7bdabd7cd2516f6562d8c3d6e0293b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Data availability", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 21, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "88ef5587-0ed1-4e91-91be-9128640109cc": {"__data__": {"id_": "88ef5587-0ed1-4e91-91be-9128640109cc", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.40, para 2](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e76759d0-a8e6-4624-ab0d-0abd0c064a73", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.40, para 2](https://elifesciences.org/articles/95135)"}, "hash": "9d4997a696a17fe6af5adb8e90b64a9bce18c541524dc3e1bd906e36b01648f1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "No data was generated in this study. All software noted in this manuscript is open source. The NeuroML core libraries can be found at", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 133, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "abacd6e4-87cb-4129-89fb-d5128c6a16d2": {"__data__": {"id_": "abacd6e4-87cb-4129-89fb-d5128c6a16d2", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.40, para 3](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4a4b1012-ae2c-4775-a58a-bec200585800", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.40, para 3](https://elifesciences.org/articles/95135)"}, "hash": "45eb6ccef1eedf255f3858b07bc137de90282181304f979285312456193ef2c5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "(copy archived at Gleeson and Sinha , 2024). Tables 3 and 4 provide links to the software packages and their source code repositories include DOI information for each software release.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 184, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "708a81ef-b237-41c3-b173-3cb0afe4de87": {"__data__": {"id_": "708a81ef-b237-41c3-b173-3cb0afe4de87", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.40, para 4](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7db6f3d0-257e-4c78-99a3-dbcb3314b0c0", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.40, para 4](https://elifesciences.org/articles/95135)"}, "hash": "f3107589aa59893ef1c93abe9cd851e7f7dc294626d82a8319ca31437b1e523c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# References", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 12, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "bfa75156-4c6f-41ea-adb9-32160a5534ea": {"__data__": {"id_": "bfa75156-4c6f-41ea-adb9-32160a5534ea", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.40, para 5](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b0a98715-16cb-4a04-a6c2-8c21d796c517", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.40, para 5](https://elifesciences.org/articles/95135)"}, "hash": "678270d8b1fc4df694fc7415227702c894d93112a9556806eba8f07f55f6594c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Abrams MB**, Bjaalie JG, Das S, Egan GF, Ghosh SS, Goscinski WJ, Grethe JS, Kotaleski JH, Ho ETW, Kennedy DN, Lanyon LJ, Leergaard TB, Mayberg HS, Milanesi L, Mou\u010dek R, Poline JB, Roy PK, Strother SC, Tang TB, Tiesinga P, et al. 2022. 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DOI:", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 255, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c83e1a0b-a43d-4417-b6fe-3773c4f5eade": {"__data__": {"id_": "c83e1a0b-a43d-4417-b6fe-3773c4f5eade", "embedding": null, "metadata": {"source document": "Publication: [SinhaEtAl2025, p.44, para 25](https://elifesciences.org/articles/95135)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e6ab0581-2be5-471e-a0d3-abf2d3e73e2e", "node_type": "4", "metadata": {"source document": "Publication: [SinhaEtAl2025, p.44, para 25](https://elifesciences.org/articles/95135)"}, "hash": "ee92a090a627c2ef2171987a4dbfaef8e2e57b9ac94e42c0262dfa7250cfd8a6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Sinha, Gleeson et al. eLife 2024;13:RP95135. DOI: https://doi.org/10.7554/eLife.95135 44 of 44", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 94, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e874d4bc-fbdb-4491-b56b-6768b9c5f24e": {"__data__": {"id_": "e874d4bc-fbdb-4491-b56b-6768b9c5f24e", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.1, para 0](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b5394099-5f58-411f-8d90-ae8293492558", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.1, para 0](https://elifesciences.org/articles/95402)"}, "hash": "c1287240afd0f66775cd1907cb2caa99449e201cb5d140dd075a6d5154d014d7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# A neurotransmitter atlas of C. elegans males and hermaphrodites", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 65, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e07c5b14-55cf-4f09-89ab-9041709743ac": {"__data__": {"id_": "e07c5b14-55cf-4f09-89ab-9041709743ac", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.1, para 1](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "84fc65d4-007b-427a-b242-7560ee49cc0b", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.1, para 1](https://elifesciences.org/articles/95402)"}, "hash": "7840ca7df9dc025f44ce83f68e8c67a71c8c9ef04ead1ba5a78ecfd8d0a04b69", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Chen Wang^1*, Berta Vidal^1, Surojit Sural^1, Curtis Loer^2, G Robert Aguilar^1, Daniel M Merritt^1, Itai Antoine Toker^1, Merly C Vogt^1\u2020, Cyril C Cros^1\u2021, Oliver Hobert^1*", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 173, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d0c01c18-8eae-401c-a8b9-221884675ff8": {"__data__": {"id_": "d0c01c18-8eae-401c-a8b9-221884675ff8", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.1, para 2](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6a5c06e8-d9a7-4d1f-a754-04b0adb30411", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.1, para 2](https://elifesciences.org/articles/95402)"}, "hash": "78be69063f3958d21c4327414d3d79555419e0e7bc727fa783c774d4ca772e89", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "^1Department of Biological Sciences, Howard Hughes Medical Institute, Columbia University, New York, United States; ^2Department of Biology, University of San Diego, San Diego, United States", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 190, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5e49118c-f6e2-4fcf-9e8d-ef627cfa960e": {"__data__": {"id_": "5e49118c-f6e2-4fcf-9e8d-ef627cfa960e", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.1, para 6](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9c5a7ab0-177c-44b3-8494-338a7cace6e6", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.1, para 6](https://elifesciences.org/articles/95402)"}, "hash": "e799a20131d70ff25aa3bd37be795ac44b37ea034dc2991447469bd510ca30c2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Present address: ^\u2020Institute for Diabetes and Cancer, Helmholtz Center, Munich, Germany; ^\u2021European Molecular Biology Institute, Heidelberg, Germany", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 148, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "16885481-099b-4cce-bebe-e0d72008700c": {"__data__": {"id_": "16885481-099b-4cce-bebe-e0d72008700c", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.1, para 7](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e08e913c-77ed-4b11-b413-94bae125189c", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.1, para 7](https://elifesciences.org/articles/95402)"}, "hash": "95a7db0a5b6c481f10d758c8f69b06b7b0c70ea670df83443065f606bf3d3192", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Competing interest: The authors declare that no competing interests exist.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 74, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "15517144-8c49-4ded-b3dc-e31b8c92b7ed": {"__data__": {"id_": "15517144-8c49-4ded-b3dc-e31b8c92b7ed", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.1, para 14](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "aedc6925-64ea-4346-86f3-194f13e588df", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.1, para 14](https://elifesciences.org/articles/95402)"}, "hash": "5eef832d24ca51c34a9616cc73f6a8d2a0697051c302fc75b807772d5c611de4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Reviewing Editor: Manuel Zimmer, University of Vienna, Austria", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 62, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "94faa45f-8fc4-4752-b483-48f75410155f": {"__data__": {"id_": "94faa45f-8fc4-4752-b483-48f75410155f", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.1, para 15](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "11785f63-1bc3-4c37-bbf8-7a508ccdaa29", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.1, para 15](https://elifesciences.org/articles/95402)"}, "hash": "1b6df2ab5a6881dc282fd82f78c32f86c6b07c289eafc09f64397b2699063142", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "\u00a9 Copyright Wang et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 221, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5b0a5e5c-eea7-446c-94df-150019a1c717": {"__data__": {"id_": "5b0a5e5c-eea7-446c-94df-150019a1c717", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.1, para 16](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6dbad9d8-2d77-4bee-a963-902a8b5b7763", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.1, para 16](https://elifesciences.org/articles/95402)"}, "hash": "73a5111fa7ecde034003c956d760eec8875a064ed94b87e30f124b32892ad7ec", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Abstract", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 11, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f1a4b07a-bd71-46e1-8eee-3e65b154e9cb": {"__data__": {"id_": "f1a4b07a-bd71-46e1-8eee-3e65b154e9cb", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.1, para 17](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e6c5b81b-b9c4-423f-bf3e-c96abc4f17a6", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.1, para 17](https://elifesciences.org/articles/95402)"}, "hash": "cb00a78eed409b90092007d769ce9ed8b40101d806b798c8997d41701f7ae113", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Mapping neurotransmitter identities to neurons is key to understanding information flow in a nervous system. It also provides valuable entry points for studying the development and plasticity of neuronal identity features. In the *Caenorhabditis elegans* nervous system, neurotransmitter identities have been largely assigned by expression pattern analysis of neurotransmitter pathway genes that encode neurotransmitter biosynthetic enzymes or transporters. However, many of these assignments have relied on multicopy reporter transgenes that may lack relevant cis-regulatory information and therefore may not provide an accurate picture of neurotransmitter usage. We analyzed the expression patterns of 16 CRISPR/Cas9-engineered knock-in reporter strains for all main types of neurotransmitters in *C. elegans* (glutamate, acetylcholine, GABA, serotonin, dopamine, tyramine, and octopamine) in both the hermaphrodite and the male. Our analysis reveals novel sites of expression of these neurotransmitter systems within both neurons and glia, as well as non-neural cells, most notably in gonadal cells. The resulting expression atlas defines neurons that may be exclusively neuropeptidergic, substantially expands the repertoire of neurons capable of co-transmitting multiple neurotransmitters, and identifies novel sites of monoaminergic neurotransmitter uptake. Furthermore, we also observed unusual co-expression patterns of monoaminergic synthesis pathway genes, suggesting the existence of novel monoaminergic transmitters. Our analysis results in what constitutes the most extensive whole-animal-wide map of neurotransmitter usage to date, paving the way for a better understanding of neuronal communication and neuronal identity specification in *C. elegans*.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1766, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5482a96b-8b5f-4f1b-a9b6-144c8cb20495": {"__data__": {"id_": "5482a96b-8b5f-4f1b-a9b6-144c8cb20495", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.1, para 18](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6b8b5034-3916-4117-ab7d-fdb3c6241cf9", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.1, para 18](https://elifesciences.org/articles/95402)"}, "hash": "fcea4a049582ab9da65488bfc74718e1dcfbd2abf9500d417ab1046162425175", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## eLife assessment", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 19, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d8992eae-f199-4e5a-8119-b522e36b3854": {"__data__": {"id_": "d8992eae-f199-4e5a-8119-b522e36b3854", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.1, para 19](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "008030d7-2604-4c75-9ab8-c2f59b494747", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.1, para 19](https://elifesciences.org/articles/95402)"}, "hash": "0b81ec79c00b99b59266a0a28aa1b5fac9a1cb16e1dab5c31fd3424784bf2987", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "This fundamental study reports the most comprehensive neurotransmitter atlas of any organism to date, using fluorescent knock-in reporter lines. The work is comprehensive, rigorous, and compelling. The tool will be used by broad audience of scientists interested in neuronal cell type differentiation and function, and could be a seminal reference in the field.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 361, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7f790f0f-0b4f-40c8-ad6c-e9126977fc71": {"__data__": {"id_": "7f790f0f-0b4f-40c8-ad6c-e9126977fc71", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.1, para 20](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f10e0878-c10c-4be2-89b8-74892e0bd876", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.1, para 20](https://elifesciences.org/articles/95402)"}, "hash": "dbda79c2fe9d9ca1cab16ddfc3445d8b1b00232ae6ab1c8f59dbf5feea732bf7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Introduction", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 15, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5484bcb0-e9c5-4446-b88f-3aec4d626b59": {"__data__": {"id_": "5484bcb0-e9c5-4446-b88f-3aec4d626b59", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.1, para 21](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "941b2c2b-c300-4f43-b5e4-d77d463fffac", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.1, para 21](https://elifesciences.org/articles/95402)"}, "hash": "0efe4da5f5e2b298700c8d6e71395e9b4c3677ceccd534acfc8b64610e15e6a7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Understanding information processing in the brain necessitates the generation of precise maps of neurotransmitter deployment. Moreover, comprehending synaptic wiring diagrams is contingent upon decoding the nature of signaling events between anatomically connected neurons. Mapping of neurotransmitter identities onto individual neuron classes also presents a valuable entry point for studying how neuronal identity features become genetically specified during development and", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 476, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0ccfd3f6-9354-4d2e-a7ba-73193dc1eaba": {"__data__": {"id_": "0ccfd3f6-9354-4d2e-a7ba-73193dc1eaba", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.2, para 0](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7417d40c-75b6-446d-b611-98fbca5f7fb5", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.2, para 0](https://elifesciences.org/articles/95402)"}, "hash": "558a1e6eafbe5da5797d6f1e1b89638c19dba158c318773bf1d58707a994bab5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "potentially modified in response to specific external factors (such as the environment) or internal factors (such as sexual identity or neuronal activity patterns).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 164, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "247c5adc-be26-47e6-afd3-10ec2a656c02": {"__data__": {"id_": "247c5adc-be26-47e6-afd3-10ec2a656c02", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.2, para 1](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a23fb1aa-df29-4442-b6b3-291eeeba48eb", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.2, para 1](https://elifesciences.org/articles/95402)"}, "hash": "ac0238d63ddb8572029c30c7c10d2557f8b093dfccb11ab8b8901867cc82c188", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The existence of complete synaptic wiring diagrams of the compact nervous system of male and hermaphrodite *Caenorhabditis elegans* nematodes raises questions about the molecular mechanisms by which individual neurons communicate with each other. *C. elegans* employs the main neurotransmitter systems that are used throughout the animal kingdom, including acetylcholine, glutamate, \u03b3-aminobutyric acid (GABA), and several monoamines (*Sulston et al., 1975; Horvitz et al., 1982; Loer and Kenyon, 1993; McIntire et al., 1993; Duerr et al., 1999; Lee et al., 1999; Duerr et al., 2001; Alkema et al., 2005; Duerr et al., 2008; Serrano-Saiz et al., 2013; Pereira et al., 2015; Gendrel et al., 2016; Serrano-Saiz et al., 2017b; Figure 1A*). Efforts to map these neurotransmitter systems to individual cell types throughout the entire nervous system have a long history, beginning with the use of chemical stains that directly detected a given neurotransmitter (dopamine) (*Sulston et al., 1975*), followed by antibody staining of neurotransmitter themselves (serotonin and GABA) (*Horvitz et al., 1982; McIntire et al., 1993*) or antibody stains of biosynthetic enzymes or neurotransmitter vesicular transporters (acetylcholine and monoamines) (*Loer and Kenyon, 1993; Duerr et al., 1999; Duerr et al., 2001; Alkema et al., 2005; Duerr et al., 2008*; see Figure 1A for an overview of these enzymes and transporters).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1412, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "25c5287b-c18f-4dcc-a5da-f0858d9e1ac8": {"__data__": {"id_": "25c5287b-c18f-4dcc-a5da-f0858d9e1ac8", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.2, para 2](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f4df5b45-1366-4605-8ed3-98d093216144", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.2, para 2](https://elifesciences.org/articles/95402)"}, "hash": "8fce0ca7e22291cd1304bec33f9416f0c340bf116c1e4bf1b86a34b4cbebadfe", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "While these early approaches proved successful in revealing neurotransmitter identities, they displayed several technical limitations. Since neurotransmitter-synthesizing or -transporting proteins primarily localize to neurites, the cellular identity of expressing cells (usually determined by assessing cell body position) often could not be unambiguously established in several, particularly cell- and neurite-dense regions of the nervous system. One example concerns cholinergic neurons, which are defined by the expression of the vesicular acetylcholine transporter UNC-17/VAChT and choline acetyltransferase CHA-1/ChAT. While mainly neurite-localized UNC-17 and CHA-1 antibody staining experiments could identify a subset of cholinergic neurons (*Duerr et al., 2001; Duerr et al., 2008*), many remained unidentified (*Pereira et al., 2015*). In addition, for GABA-producing neurons, it became apparent that antibody-based GABA detection was dependent on staining protocols, leading to the identification of \u2018novel\u2019 anti-GABA-positive neurons, i.e., GABAergic neurons, more than 20 years after the initial description of GABAergic neurons (*McIntire et al., 1993; Gendrel et al., 2016*).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1191, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "314d1654-8216-4cf9-8478-9ad06cce0531": {"__data__": {"id_": "314d1654-8216-4cf9-8478-9ad06cce0531", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.2, para 3](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3c1f39ce-0477-401a-8f31-edb4551f7737", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.2, para 3](https://elifesciences.org/articles/95402)"}, "hash": "ee8b8686fe67c5449e820b665cd05a80058e13b58c48ae6286749f70505488f8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "An alternative approach to mapping neurotransmitter usage has been the use of reporter transgenes. This approach has the significant advantage of allowing the fluorophore to either fill the entire cytoplasm of a cell or to be targeted to the nucleus, thereby facilitating neuron identification. However, one shortcoming of transgene-based reporter approaches is that one cannot be certain that a chosen genomic region, fused to a reporter gene, indeed contains all cis-regulatory elements of the respective locus. In fact, the first report that described the expression of the vesicular glutamate transporter EAT-4, the key marker for glutamatergic neuron identity, largely underestimated the number of eat-4/VGLUT-positive and, hence, glutamatergic neurons (*Lee et al., 1999*). The introduction of fosmid-based reporter transgenes has largely addressed such concerns, as these reporters, with their 30\u201350 Kb size, usually cover entire intergenic regions (*Sarov et al., 2012*). Indeed, such fosmid-based reporters have been instrumental in describing the supposedly complete *C. elegans* glutamatergic nervous system, defined by the expression of eat-4/VGLUT (*Serrano-Saiz et al., 2013*), as well as the supposedly complete set of cholinergic (*Pereira et al., 2015*) and GABAergic neurons (*Gendrel et al., 2016*).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1318, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ab5f2939-f877-4c23-9eff-20cbf93c2588": {"__data__": {"id_": "ab5f2939-f877-4c23-9eff-20cbf93c2588", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.2, para 4](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "52fe1624-978b-43ea-8e02-7a1fb4756dba", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.2, para 4](https://elifesciences.org/articles/95402)"}, "hash": "728e00d1952a9164a5f793e37425e59b04d823184994df03e2e8c7527e0f4cca", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "However, even fosmid-based reporters may not be the final word. In theory, they may still miss distal cis-regulatory elements. Moreover, the multicopy nature of transgenes harbors the risk of overexpression artifacts, such as the titrating of rate-limiting negative regulatory mechanisms. Also, RNAi-based silencing mechanisms triggered by the multicopy nature of transgenic reporter arrays have the potential to dampen the expression of reporter arrays (*Nance and Frokjaer-Jensen, 2019*). One way to get around these limitations, while still preserving the advantages of reporter gene approaches, is to generate reporter alleles in which an endogenous locus is tagged with a reporter cassette, using CRISPR/Cas9 genome engineering. Side-by-side comparisons of fosmid-based reporter expression patterns with those of knock-in reporter alleles indeed revealed several instances of discrepancies in expression patterns of homeobox genes (*Reilly et al., 2022*).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 960, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0a71e164-19fa-4c3c-8878-8ba3f28cd046": {"__data__": {"id_": "0a71e164-19fa-4c3c-8878-8ba3f28cd046", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.2, para 5](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2736f50f-c561-486d-9fb7-919f071eceac", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.2, para 5](https://elifesciences.org/articles/95402)"}, "hash": "1c69ecf8d8ec1c28b8d0940533b4ff14a13b6b6e5ed00d780014129fe27f507a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "An indication that previous neurotransmitter assignments may not have been complete was provided by recent single-cell RNA (scRNA) transcriptomic analyses of the hermaphrodite nervous", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 183, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1e10e8e2-991f-4e8e-8db3-918553cf8c45": {"__data__": {"id_": "1e10e8e2-991f-4e8e-8db3-918553cf8c45", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 0](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0939f92e-7222-484d-a47e-64de07d71203", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 0](https://elifesciences.org/articles/95402)"}, "hash": "eab6d910547c1ae50cbfe69d9b47db5ea3bca8f838dd5efb81968bc6cab59857", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# eLife Tools and resources", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 27, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b92c7106-c2e3-4f16-a7bc-01b82b2b4f32": {"__data__": {"id_": "b92c7106-c2e3-4f16-a7bc-01b82b2b4f32", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 2](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b1d4fbdf-d114-43f0-b05c-d9e5919ee6a3", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 2](https://elifesciences.org/articles/95402)"}, "hash": "7c5559be50f307dd0e55cfe6410e3e237dfeee93b134477f4ce817d3ed689d06", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## A", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "13eecb27-ebf8-466b-a969-a849069ba081": {"__data__": {"id_": "13eecb27-ebf8-466b-a969-a849069ba081", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 3](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2ab922c3-feb0-462c-a568-d9256995b9c7", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 3](https://elifesciences.org/articles/95402)"}, "hash": "1f795ad1fecef158631fe87125b237dfa50b304130c26db1abd2f6b02dac790e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Cholinergic neurons", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 23, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8d46827b-40d8-4373-b58d-6706683c30dd": {"__data__": {"id_": "8d46827b-40d8-4373-b58d-6706683c30dd", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 4](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "777cd5e6-0527-4779-b667-cbdb942543a8", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 4](https://elifesciences.org/articles/95402)"}, "hash": "c82f138e8b6c687b26340f4566d1766236672bf79b4c853dcce878e3d649ab04", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* ChaT\n  * `cha-1`\n* ACh\n* VAChT\n  * `unc-17`\n* CHT1\n  * `cho-1`", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 64, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "61f58b16-c891-4ef3-9ab5-b06589fb3120": {"__data__": {"id_": "61f58b16-c891-4ef3-9ab5-b06589fb3120", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 5](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1e4cdb74-ffad-42bb-8ca4-3e87798d4ef0", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 5](https://elifesciences.org/articles/95402)"}, "hash": "345ba8d60d3ed035e1a4baef068377cc4a85e3a46600452513bcb50478ac297e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### GABAergic neurons", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 21, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "305fc3dc-ece4-486c-ad17-34ea499923a6": {"__data__": {"id_": "305fc3dc-ece4-486c-ad17-34ea499923a6", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 6](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5d1b889d-ad7c-4dea-9fa2-2e87719942d8", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 6](https://elifesciences.org/articles/95402)"}, "hash": "f8a0dd8a65a190f4c1001a2a82991602d0b8188e968b05f9f83b3cdb27447a67", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* GAD\n  * `unc-25`\n* GABA\n* VGAT\n  * `unc-47`\n* GAT\n  * `snf-11`", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 64, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "99c34237-c46e-4b21-a381-0f50ca0a3c8f": {"__data__": {"id_": "99c34237-c46e-4b21-a381-0f50ca0a3c8f", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 7](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "678ca406-78d3-44ee-8320-1ec3fdbe92e6", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 7](https://elifesciences.org/articles/95402)"}, "hash": "6331eaa88eebd0a9c6a425cbb6e56d865807b5b87f03b0466656d950124f072c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Glutamatergic neurons", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 25, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "55b4da8e-8190-44db-9b83-571f5654c6bb": {"__data__": {"id_": "55b4da8e-8190-44db-9b83-571f5654c6bb", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 9](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cd4ac07c-87dc-4163-b0f1-4a26fae29c68", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 9](https://elifesciences.org/articles/95402)"}, "hash": "ae3ec3628b1770b6e4517a2dde93fec547ed8c2a17b656b4ecc19a704a11608a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Serotonergic neurons", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 24, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "333698e0-5ab9-4912-818a-9cd3424dfb72": {"__data__": {"id_": "333698e0-5ab9-4912-818a-9cd3424dfb72", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 10](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1270bef3-44f7-44ed-9310-9ac93f7150b3", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 10](https://elifesciences.org/articles/95402)"}, "hash": "46c404c493d36539a95e20756b2fd77d640b6d013147197b3f9d85da2e32691b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* TPH\n  * `tph-1`\n* Trp\n* 5-HTP\n* 5-HT\n* VMAT\n  * `cat-1`\n* SERT\n  * `mod-5`", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 76, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0b18716c-c50d-4aa3-9853-ccadba20ad35": {"__data__": {"id_": "0b18716c-c50d-4aa3-9853-ccadba20ad35", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 11](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "608f8f48-93ab-4dc6-b8f7-67b1bb2d1cf3", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 11](https://elifesciences.org/articles/95402)"}, "hash": "e1fb7d5dc40ad6d4c6e8a3be5ec704dd518c751ec21441c5d2521dff89153fa0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Tyraminergic neurons", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 24, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e4a428e4-7f7e-454c-8522-baf8b8cd48f8": {"__data__": {"id_": "e4a428e4-7f7e-454c-8522-baf8b8cd48f8", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 12](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "14ad55a7-6dfd-4e04-b61c-3c859d7d4c69", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 12](https://elifesciences.org/articles/95402)"}, "hash": "7f0307d6a61568c4ed76ad17fedbd3045c440ebd914581a802d1f5c60dd7ef5d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* TDC\n  * `tdc-1`\n* Tyr\n* TA\n* VMAT\n  * `cat-1`\n* OCT\n  * `oct-1`", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 65, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cc0b1414-9db3-4771-bef4-a11a2a0d250e": {"__data__": {"id_": "cc0b1414-9db3-4771-bef4-a11a2a0d250e", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 13](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1ab3e634-6a43-44e1-9117-ecbe484df1ea", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 13](https://elifesciences.org/articles/95402)"}, "hash": "9f487dbc3663bc0c6d0314f147189eb62804b7f35403f239b1541d72b482cdc9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Octopaminergic neurons", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 26, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c35c008e-3fbd-4d86-8924-53625cccd416": {"__data__": {"id_": "c35c008e-3fbd-4d86-8924-53625cccd416", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 14](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8914d9ef-ddc9-42fe-b952-865968673f71", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 14](https://elifesciences.org/articles/95402)"}, "hash": "96c1dbb63dac82789d3fec68fa15569f577f566ed69fa7f8c8b8626aed82d1a9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* TDC\n  * `tdc-1`\n* Tyr\n* TBH\n  * `tbh-1`\n* TA\n* OA\n* VMAT\n  * `cat-1`", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 70, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b423e375-de5a-4769-a0b8-a97e0e17190b": {"__data__": {"id_": "b423e375-de5a-4769-a0b8-a97e0e17190b", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 15](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0a4766b5-57f0-4a97-993d-f076252e41eb", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 15](https://elifesciences.org/articles/95402)"}, "hash": "e1998cb02d6fed4afc9ac2d3766b60e49dd948315bb3ad5a615a6a731e1f4f11", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Dopaminergic neurons", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 24, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "867aeba4-78af-448d-ab6a-eca671809842": {"__data__": {"id_": "867aeba4-78af-448d-ab6a-eca671809842", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 16](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fb6a849a-6759-4880-8b0a-d4ddf52215dc", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 16](https://elifesciences.org/articles/95402)"}, "hash": "d6562835f8cf7bf19eedd8cba8467125b0651bc21e75367a626be93349756c94", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* TH\n  * `cat-2`\n* Tyr\n* AAAD\n  * `bas-1`\n* L-DOPA\n* DA\n* VMAT\n  * `cat-1`\n* DAT\n  * `dat-1`", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 92, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ae73170d-8d1e-4e1c-b47b-9c9ab4921f7b": {"__data__": {"id_": "ae73170d-8d1e-4e1c-b47b-9c9ab4921f7b", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 17](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4120e2e6-e812-41dd-8660-88439c50060c", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 17](https://elifesciences.org/articles/95402)"}, "hash": "0e3c4c7bf7fca1f1935abbcd6c30ee07d73fe39daff13245d5dc9f66861e6e6a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## B", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4cdb8c85-9ad0-4a7b-9652-e28da8a511a4": {"__data__": {"id_": "4cdb8c85-9ad0-4a7b-9652-e28da8a511a4", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 18](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f82deb96-281e-413f-8c25-f74525f0fd9b", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 18](https://elifesciences.org/articles/95402)"}, "hash": "668f03a0f55ce0019c3badb0c749922cdf4197134cd263db76d08e143d024d0e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### eat-4", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 9, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "45203509-a22d-410b-8b61-98b5f1bcb2ff": {"__data__": {"id_": "45203509-a22d-410b-8b61-98b5f1bcb2ff", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 19](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7c4705e7-f5b0-4bbb-a232-40b685583fe4", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 19](https://elifesciences.org/articles/95402)"}, "hash": "26587dd9d88ec561d18fce55a73ee488d2bf6ab4277f79c7a23114e203f7aa3b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* * threshold\n* 4\n* 3\n* 2\n* 1\n* OLL\n* OLQ\n* URY\n* DVC\n* AUA\n* IL1\n* RIC\n* BAG\n* PVR\n* LUA\n* ALM\n* RIA\n* PHB\n* M3\n* PHC\n* ADA\n* OFF\n* AWC\n* ASER\n* ASH\n* I5\n* AIZ\n* AIB\n* RIM\n* ON\n* RIG\n* PVN\n* ADL\n* FLP\n* PQR\n* MI\n* ASER\n* PVQ\n* AFD\n* AQR\n* ASK\n* DVA\n* AIM\n* PLM\n* I6\n* ASG\n* PHA\n* PVD\n* AVM\n* RMD\\_LR\n* RMD\\_DV\n* M5\n* URB\n* I4\n* PVM\n* IL2\\_DV", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 342, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "05403b99-19e1-445e-b19c-0da28b23dde0": {"__data__": {"id_": "05403b99-19e1-445e-b19c-0da28b23dde0", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 20](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cfb4b5c8-468c-45ab-949f-e9dd2a2dd039", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 20](https://elifesciences.org/articles/95402)"}, "hash": "d60e1240bdb2c76c4e5a1f95455f5694940df1c941d8135193e4ae241ec10b85", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### unc-17", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 10, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "053d8bc3-6eca-410d-a774-129227d60ea9": {"__data__": {"id_": "053d8bc3-6eca-410d-a774-129227d60ea9", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 21](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "65ed30b8-4a4a-4812-8a44-9077babb7f81", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 21](https://elifesciences.org/articles/95402)"}, "hash": "e01634e3e8ed4f879935dde24c1f8995cce0d6352f9dbc52d065cf7b7949cc2d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* * threshold\n* 4\n* 3\n* 2\n* 1\n* DA\n* AS\n* DB\n* SAB\n* VC\\_4\\_5\n* VA12\n* DA9\n* VB\n* VC\n* M4\n* IL2\\_LR\n* VA\n* DB01\n* PDA\n* SIA\n* PVC\n* RMD\\_DV\n* SMD\n* RMD\\_LR\n* SIB\n* RIH\n* MC\n* ALN\n* M5\n* M1\n* URA\n* RIF\n* AVD\n* IL2\\_DV\n* VB01\n* SDQ\n* M2\n* SMB\n* VB02\n* RIV\n* RIP\n* RMF\n* ADF\n* AIA\n* I1\n* I3\n* SAA\n* URX\n* RIR\n* AIY\n* AVA\n* HSN\n* AVE\n* AVE\n* PVP\n* URB\n* AIN\n* RMH\n* PLN\n* DVA\n* AWB\n* ASJ\n* RID\n* LUA\n* AWA\n* PDB\n* AWC\\_ON\n* CEP\n* ASE\n* PVQ\n* AIM\n* AQR\n* AVH\n* AUA\n* RIM\n* DVB\n* RIA\n* RME\\_DV\n* RIC\n* AVF", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 499, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c67d795d-3fde-46a6-9579-63d8ea903f9f": {"__data__": {"id_": "c67d795d-3fde-46a6-9579-63d8ea903f9f", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 22](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "021b845d-1a36-412b-8558-4f3bc1f67074", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 22](https://elifesciences.org/articles/95402)"}, "hash": "da271b36a4b14ac05d5c89283b644a962d8431d3071860e02caa13dbdcd65b78", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### unc-25", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 10, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a6ccc69d-ab18-4a5a-af5a-c6351759f37b": {"__data__": {"id_": "a6ccc69d-ab18-4a5a-af5a-c6351759f37b", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 23](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "063c22e9-0e68-4d51-876c-84fa827ba3e9", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 23](https://elifesciences.org/articles/95402)"}, "hash": "371f644cee1b43eca8390aee79bbb585cd413d695a66959d4ba9e4f26ea9ce74", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* threshold\n* 4\n* 3\n* 2\n* 1\n* VD\\_DD\n* RME\\_LR\n* RME\\_DV\n* DVB\n* AVL\n* RIS\n* RIB\n* AVH\n* PVT\n* AWA", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 98, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7a446ed0-780d-4c2f-bc39-537b77fa69e4": {"__data__": {"id_": "7a446ed0-780d-4c2f-bc39-537b77fa69e4", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 24](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "855f8c1b-26bd-4672-9476-3437e9b5a729", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 24](https://elifesciences.org/articles/95402)"}, "hash": "aa94713d1f115bfc5e57bcb9c14cc6cfe8465244788748db786d6f8a7d032652", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### unc-47", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 10, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "951882f1-06a2-46d4-a151-c0796933d891": {"__data__": {"id_": "951882f1-06a2-46d4-a151-c0796933d891", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 25](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a5aeefc3-b45f-4224-aa48-058b6907ac2f", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 25](https://elifesciences.org/articles/95402)"}, "hash": "58c04d788edc2419444c99104cb2ab5d7b9747c1b813052a39f04a227a6581aa", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* threshold\n* 4\n* 3\n* 2\n* 1\n* DVB\n* VD\\_DD\n* AVL\n* RME\\_LR\n* AIN\n* RME\\_DV\n* SIA\n* RIS\n* RIB\n* SDQ\n* RIF\n* DVC\n* URX\n* AVG\n* PLN\n* I3\n* I6\n* DVA\n* M2\n* M1\n* NSM\n* SMD\n* MI\n* RID\n* PVT", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 183, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "679996ff-b58b-41ab-a971-b82b10ee9145": {"__data__": {"id_": "679996ff-b58b-41ab-a971-b82b10ee9145", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 26](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f485a33c-1fa6-48ce-9c2f-3521abd15c5b", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 26](https://elifesciences.org/articles/95402)"}, "hash": "62e86ef2a30db82f0e2352b0b5fd8374f304cdcd30ac9befb0485707854b38a3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "expression of fosmid-based reporter (with the exception of `cat-2`, `tdc-1`, and `tbh-1`, which were transgene-based reporters)\nno expression of fosmid-based reporter (\\* expression observed with reporter allele as described in this paper)\nblue font: direct staining for neurotransmitter or endogenous protein", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 309, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c1b530d9-1049-4f64-8541-16aa1d48a833": {"__data__": {"id_": "c1b530d9-1049-4f64-8541-16aa1d48a833", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 27](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a84ee797-73c9-4e92-ae7b-fe4066a1e78a", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 27](https://elifesciences.org/articles/95402)"}, "hash": "6d89afdf6599a9864730cb255a47e194dead32bd04e33cb9da4b151f6ebaa2f2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### tph-1", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 9, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "336f0938-6fc5-4686-abc4-e598e074488d": {"__data__": {"id_": "336f0938-6fc5-4686-abc4-e598e074488d", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 28](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0747dda8-5273-4d14-a916-51b7c38c940c", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 28](https://elifesciences.org/articles/95402)"}, "hash": "19ef0fb724533b797c4092efd86e644f94905ec83de7b414cdaf03c1d13d0c3c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* threshold\n* 4\n* 3\n* 2\n* 1\n* HSN\n* NSM\n* ADF\n* AFD\n* MI\n* I1\n* VC\\_4\\_5", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 72, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f8ca0ccf-1f51-4e0e-874a-0a2d47cd2fd7": {"__data__": {"id_": "f8ca0ccf-1f51-4e0e-874a-0a2d47cd2fd7", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 29](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "292a6608-ccaa-47f2-8050-e52da2a479c3", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 29](https://elifesciences.org/articles/95402)"}, "hash": "60828643bc583ae01cad33577cfae40bd334de02b3e7f41a6b622d7a57093676", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### bas-1", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 9, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7bc0d302-0297-4a4d-ab13-3583e2fe4ef3": {"__data__": {"id_": "7bc0d302-0297-4a4d-ab13-3583e2fe4ef3", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 30](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "40e61e8c-516e-4b51-8327-6eaf6df50af5", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 30](https://elifesciences.org/articles/95402)"}, "hash": "c9817bf6b1af8d63fadf85c29daf08667217d1fc1811d27d2c509a6544868ab5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* threshold\n* 4\n* 3\n* 2\n* 1\n* HSN\n* NSM\n* PDE\n* CEP\n* ADF\n* URB\n* PWT\n* PVT", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 75, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1dfae0c9-f23d-4674-ba0a-64e605aedb9c": {"__data__": {"id_": "1dfae0c9-f23d-4674-ba0a-64e605aedb9c", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 31](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "74506b23-0151-4981-ac8c-aa92328f5423", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 31](https://elifesciences.org/articles/95402)"}, "hash": "c756219ac8ad78263c013d0738679231b7435f62e48a756fcc5497fadf11f79c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### cat-1", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 9, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ea177d90-ad6a-4412-b27a-bb9856265d49": {"__data__": {"id_": "ea177d90-ad6a-4412-b27a-bb9856265d49", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 32](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3ce465ca-59e2-4ecc-9e24-d1a5fd0cbbb8", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 32](https://elifesciences.org/articles/95402)"}, "hash": "41efc8c377a7283bc3485e482ed4515beeef8e4155217ff0541b8fe5d35afc2d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* threshold\n* 4\n* 3\n* 2\n* 1\n* PDE\n* NSM\n* RIM\n* HSN\n* VC\\_4\\_5\n* RIR\n* RIC\n* ADF\n* RIH\n* ADE\n* CAN\n* CEP\n* AVM\n* M3\n* BAG\n* ASI\n* AQR\n* AWC\\_OFF\n* PVR\n* PVT", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 156, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "90762845-a5cf-47d3-90f4-225d8a79ced6": {"__data__": {"id_": "90762845-a5cf-47d3-90f4-225d8a79ced6", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 33](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "82b294e7-917e-441b-aff4-67f3e67d63fb", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 33](https://elifesciences.org/articles/95402)"}, "hash": "715e08b119c0bfe82a3b75fc2c161c34b3e52488f6940f56b0f915d684720899", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### cat-2", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 9, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "57679489-1c34-4634-ad23-01be3d78298c": {"__data__": {"id_": "57679489-1c34-4634-ad23-01be3d78298c", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 35](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ad58457b-4b43-48dd-95f6-eeff5d1331b6", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 35](https://elifesciences.org/articles/95402)"}, "hash": "a00c0a2730021cc5c589293f9dd21657d337bbc1b85dffea668e753b42e12328", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### tdc-1", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 9, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e8833ce8-2c51-4a21-9cee-6a441cf97534": {"__data__": {"id_": "e8833ce8-2c51-4a21-9cee-6a441cf97534", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 37](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fa94320c-6713-417d-a825-70a534ca594b", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 37](https://elifesciences.org/articles/95402)"}, "hash": "408150eee7642888288154153c766d1adfb90c3c1d724358fcaddb572accde7d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### tbh-1", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 9, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "815489b0-8ba4-40cf-aca6-9f79eb28ed7d": {"__data__": {"id_": "815489b0-8ba4-40cf-aca6-9f79eb28ed7d", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 38](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cdc7b049-e755-4f53-a1fd-bb8dd98f99d7", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 38](https://elifesciences.org/articles/95402)"}, "hash": "7dd55e45ea4d45c7ee14ef9d9859dcc6e3283f891ed0f23d0ebc6e43bec9e221", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* threshold\n* 4\n* 3\n* 2\n* 1\n* RIC\n* PDA\n* IL2\\_LR\n* IL2\\_DV\n* BAG", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 65, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "dc7f8ff1-5704-4402-aad4-0cdba4c589b9": {"__data__": {"id_": "dc7f8ff1-5704-4402-aad4-0cdba4c589b9", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 39](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "64a1abb2-d7c2-4d52-ae46-5443b3f1d86c", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 39](https://elifesciences.org/articles/95402)"}, "hash": "7ca7c8c694c38e3d4f98e904675f61a9c1e162c75cdd1495a292adbb9589f9fe", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Figure 1.** Background on genes examined in this paper. (A) Neurotransmitter synthesis and transport pathways. TH = tyrosine hydroxylase; TDC = tyrosine decarboxylase; TBH = tyramine \u03b2-hydroxylase; TPH = tryptophan hydroxylase; GAD = glutamic acid decarboxylase; AAAD = aromatic amino acid decarboxylase; VMAT = vesicular monoamine transporter; VAChT = vesicular acetylcholine transporter; VGAT = vesicular \u03b3-aminobutyric acid (GABA) transporter; Ch = choline; ACh = acetylcholine; TA = tyramine; OA = octopamine; DA = dopamine. CHT1 = choline uptake transporter; SERT = serotonin uptake transporter; OCT = organic cation transporter; DAT = dopamine uptake transporter; GAT = GABA uptake transporter. Taken and modified from Figure 6 of Hobert, 2013. (B) Graphic comparison of single-cell RNA (scRNA) expression data and previously reported reporter expression data. See Supplementary file 1 for a more comprehensive version that includes expression of reporter genes in cells that show no scRNA transcripts. Note that scRNA expression values for `eat-4` and `unc-47` can be unreliable because they were overexpressed to isolate individual neurons for scRNA analysis (Taylor et al., 2021).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1191, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f7ac0ae3-f329-4225-b37d-0016a28f9b93": {"__data__": {"id_": "f7ac0ae3-f329-4225-b37d-0016a28f9b93", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 40](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "761089ee-b6d2-495c-85c2-6ced12d8dc6f", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 40](https://elifesciences.org/articles/95402)"}, "hash": "d10523c48b42b5b0bad59c887fd5fe553caaad819477700115770e9495015179", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The online version of this article includes the following figure supplement(s) for figure 1:", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 92, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e12fee54-c9ab-4654-a4fd-27fd1f3d90cf": {"__data__": {"id_": "e12fee54-c9ab-4654-a4fd-27fd1f3d90cf", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 41](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "22e458d0-ce76-4307-8938-b8a0d42af91f", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.3, para 41](https://elifesciences.org/articles/95402)"}, "hash": "f4d99f29091f744c823b91db78e0b5e88f40e0ef643caa8df4947c68571ec726", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Figure supplement 1.** Use of aromatic amino acid decarboxylases (AAADs) in *C. elegans*.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 91, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "40789be0-eb72-4d22-a157-ab22a56c2889": {"__data__": {"id_": "40789be0-eb72-4d22-a157-ab22a56c2889", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.4, para 1](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "71ed96d6-2eeb-41f9-8569-151ef91ba474", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.4, para 1](https://elifesciences.org/articles/95402)"}, "hash": "4a7fb8dcb8e82a8e107c427351434c87022a329869b21607cd5eff379e7a1a34", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "system of L4 stage animals by the CeNGEN consortium (*Taylor et al.*, 2021). As we describe in this paper in more detail, transcripts for several neurotransmitter-synthesizing enzymes or transporters were detected in a few cells beyond those previously described to express the respective reporter genes. This motivated us to use CRISPR/Cas9 engineering to fluorescently tag a comprehensive panel of genetic loci that code for neurotransmitter-synthesizing, -transporting, and -uptaking proteins ('neurotransmitter pathway genes'). Using the landmark strain NeuroPAL for neuron identification (*Yemini et al.*, 2021), we identified novel sites of expression of most neurotransmitter pathway genes. Furthermore, we used these reagents to expand and refine neurotransmitter maps of the entire nervous system of the *C. elegans* male, which contains almost 30% more neurons than the nervous system of the hermaphrodite yet lacks a reported scRNA transcriptome atlas. Together with the NeuroPAL cell-identification tool, these reporter alleles allowed us to substantially improve the previously described neurotransmitter map of the male nervous system (*Serrano-Saiz et al.*, 2017b). Our analysis provides insights into the breadth of usage of each individual neurotransmitter system, reveals instances of co-transmitter use, indicates the existence of neurons that may entirely rely on neuropeptides instead of classic neurotransmitters, reveals sexual dimorphisms in neurotransmitter usage, and suggests the likely existence of presently unknown neurotransmitters.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1563, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "babc0113-c5d2-4641-9f13-447706a921da": {"__data__": {"id_": "babc0113-c5d2-4641-9f13-447706a921da", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.4, para 2](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c0369ccd-e65e-4e9f-a9f6-7e67a25cbc6e", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.4, para 2](https://elifesciences.org/articles/95402)"}, "hash": "89e670108bd94ae5bd6e1466a0111cdd8e190c9c06c7d3bfb259580ddf0ed68a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Results", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 10, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2373c804-7a0f-4f91-897f-537166f9b40f": {"__data__": {"id_": "2373c804-7a0f-4f91-897f-537166f9b40f", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.4, para 3](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "13c54738-a693-4be4-a596-3128fe739118", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.4, para 3](https://elifesciences.org/articles/95402)"}, "hash": "3ede01cacab1b655bd6e8b4258864e94f40098e1a5a61bfd6319101e268c1451", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Comparing CeNGEN scRNA data to reporter gene data", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 53, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8c6c151d-481c-47cd-a0d1-1720d078ab60": {"__data__": {"id_": "8c6c151d-481c-47cd-a0d1-1720d078ab60", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.4, para 4](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fd9db0b9-835f-4e33-a4a4-1e43c417c0c3", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.4, para 4](https://elifesciences.org/articles/95402)"}, "hash": "f1632d84e00461801576f66297eba555b8c9d4a3e94f0b8a73102f51eaf20f69", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "To investigate the neurotransmitter identity of neurons throughout the entire *C. elegans* nervous system of both sexes, we consider here the expression pattern of the following 15 genetic loci (see also Figure 1A):", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 215, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f1461532-a697-4126-b218-9e552efc3371": {"__data__": {"id_": "f1461532-a697-4126-b218-9e552efc3371", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.4, para 5](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "591ee818-0bd9-4e7c-a6b6-18ce0d692621", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.4, para 5](https://elifesciences.org/articles/95402)"}, "hash": "35cef36d3d2635898090296c5ab1006213fc03813e59a249cffbb3697fccf12f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* a. *eat-4/VGLUT*: expression of the vesicular glutamate transporter is alone sufficient to define glutamatergic neuron identity (*Lee et al.*, 1999; *Serrano-Saiz et al.*, 2013).\n* b. *unc-17/VAChT*: expression of the vesicular acetylcholine transporter, located in an operon together with the acetylcholine-synthesizing gene *cha-1/ChAT* (*Alfonso et al.*, 1994), defines cholinergic neurons (*Duerr et al.*, 2001; *Duerr et al.*, 2008; *Pereira et al.*, 2015).\n* c. *unc-25/GAD*, *unc-47/VGAT*, and its sorting co-factor *unc-46/LAMP*: expression of these three genes defines neurons that synthesize and release GABA (*McIntire et al.*, 1993; *McIntire et al.*, 1997; *Jin et al.*, 1999; *Schuske et al.*, 2007; *Gendrel et al.*, 2016). Additional neurons that we classify as GABAergic are those that do not synthesize GABA (*unc-25/GAD*-negative), but take up GABA from other neurons (based on anti-GABA antibody staining) and are expected to release GABA based on *unc-47/VGAT* expression (*Gendrel et al.*, 2016). *unc-47/VGAT* expression without any evidence of GABA synthesis or uptake (*unc-25/GAD*- and anti-GABA-negative) is indicative of an unknown transmitter being present in these cells and utilizing *unc-47/VGAT* for vesicular secretion.\n* d. *tph-1/TPH* and *bas-1/AAAD*: the co-expression of these two biosynthetic enzymes, together with the co-expression of the monoamine vesicular transporter *cat-1/VMAT*, defines all serotonin-synthesizing and -releasing neurons (Figure 1A; *Horvitz et al.*, 1982; *Duerr et al.*, 1999; *Sze et al.*, 2000; *Hare and Loer*, 2004).\n* e. *cat-2/TH* and *bas-1/AAAD*: the co-expression of these two biosynthetic enzymes, together with the co-expression of the monoamine vesicular transporter *cat-1/VMAT*, defines all dopamine-synthesizing and -releasing neurons (Figure 1A; *Sulston et al.*, 1975; *Duerr et al.*, 1999; *Lints and Emmons*, 1999; *Hare and Loer*, 2004).\n* f. *tdc-1/TDC*: defines, together with *cat-1/VMAT*, all tyramine-synthesizing and -releasing neurons (Figure 1A; *Alkema et al.*, 2005).\n* g. *tbh-1/TBH*: expression of this gene, in combination with that of *tdc-1/TDC* and *cat-1/VMAT*, defines octopamine-synthesizing and -releasing neurons (Figure 1A; *Alkema et al.*, 2005).\n* h. *cat-1/VMAT*: expression of this vesicular monoamine transporter defines all four above-mentioned monoaminergic neurons (serotonin, dopamine, tyramine, octopamine) (*Duerr et al.*, 1999), but as described and discussed below, it may also define additional sets of monoaminergic neurons.\n* i. *hdl-1/AAAD*: *hdl-1*, a previously uncharacterized gene, encodes the only other AAAD with sequence similarity to the *bas-1* and *tdc-1* AAAD enzymes that produce other bona fide", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2734, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9e9b5228-f8e8-480d-bc1b-0a058ee485dd": {"__data__": {"id_": "9e9b5228-f8e8-480d-bc1b-0a058ee485dd", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.5, para 0](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6cdcd301-4101-479b-82b7-1acd17d6ce9b", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.5, para 0](https://elifesciences.org/articles/95402)"}, "hash": "da5d308ee957fa12d8e6d6167d65f09c832b6e09198eb25ffda10c53c241dece", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "monoamines (Figure 1\u2014figure supplement 1; Hare and Loer, 2004). hdl-1 expression may therefore, in combination with cat-1/VMAT, identify neurons that produce and release trace amines of unknown identity.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 203, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "02b85ff9-725e-4687-a5d1-2a6609b50c88": {"__data__": {"id_": "02b85ff9-725e-4687-a5d1-2a6609b50c88", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.5, para 1](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6242e844-7964-48fd-b945-bdc9c1e36eab", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.5, para 1](https://elifesciences.org/articles/95402)"}, "hash": "41b7238d2ed23796289e806998e1a229fe1c9bae25e7662485ff2ca91935f942", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "j. snf-3/BGT1/SLC6A12: this gene encodes the functionally validated ortholog of the vertebrate betaine uptake transporter SLC6A12 (i.e. BGT1) (Peden et al., 2013). In combination with the expression of cat-1/VMAT, which synaptically transports betaine (Hardege et al., 2022), snf-3 expression may identify neurons that utilize betaine as a synaptically released neurotransmitter to gate betaine-gated ion channels, such as ACR-23 (Peden et al., 2013) or LGC-41 (Hardege et al., 2022).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 484, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "abbc17c3-740b-48ad-8563-1d65526cdcba": {"__data__": {"id_": "abbc17c3-740b-48ad-8563-1d65526cdcba", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.5, para 2](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "918bfd6b-8c33-42ab-b35d-6714ec4543d6", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.5, para 2](https://elifesciences.org/articles/95402)"}, "hash": "40b458a275d32ef703d2463a1af489277c027461a4d7e2b08fbb7aae7d3c5f41", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "k. mod-5/SERT: this gene codes for the functionally validated ortholog of the vertebrate serotonin uptake transporter SERT (Ranganathan et al., 2001), which defines neurons that take up serotonin independently of their ability to synthesize serotonin and, depending on their expression of cat-1/VMAT, may either re-utilize serotonin for synaptic signaling or serve as serotonin clearance neurons.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 396, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3256bf09-20fa-4363-b77d-6889e77eb8a4": {"__data__": {"id_": "3256bf09-20fa-4363-b77d-6889e77eb8a4", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.5, para 3](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "21f0c4d9-12bf-46c6-bf16-40cb9c77ce90", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.5, para 3](https://elifesciences.org/articles/95402)"}, "hash": "83e48dc178712e424cf4addf0d8d5aa9faa8d8bff8c46ba1ae05c715518fbda3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "l. oct-1/OCT: this gene encodes the closest representative of the OCT subclass of SLC22 organic cation transporters (Zhu et al., 2015), several members of which are selective uptake transporters of tyramine (Breidert et al., 1998; Berry et al., 2016). Its expression or function in the nervous system had not previously been analyzed in C. elegans.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 348, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e3b157da-a6ea-449c-bec5-f5cf4dd2a855": {"__data__": {"id_": "e3b157da-a6ea-449c-bec5-f5cf4dd2a855", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.5, para 4](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8733505d-0e7c-4f6f-9776-342586f7e278", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.5, para 4](https://elifesciences.org/articles/95402)"}, "hash": "825d3d4383ca9a73041f8c82921f8f74fb4e9c5e0164f05d3c88ea28e376ec98", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "For all these 15 genetic loci, we compared scRNA transcriptome data from the CeNGEN scRNA atlas (at all four available stringency levels; Taylor et al., 2021) to previously published reporter and antibody staining data. As shown in Figure 1B and Supplementary file 1, such comparisons reveal the following: (a) scRNA data support the expression of genes in the vast majority of neurons in which those genes were found to be expressed with previous reporter gene approaches. In most cases, this is true even at the highest threshold levels for scRNA detection. (b) Vice versa, reporter gene expression supports scRNA transcriptome data for a specific neurotransmitter system in the great majority of cells. (c) In spite of this congruence, there were several discrepancies between reporter data and scRNA data. Generally, while valuable, scRNA transcriptome data cannot be considered the final word for any gene expression pattern assignments. Lack of detection of transcripts could be a sensitivity issue and, conversely, the presence of transcripts does not necessarily indicate that the respective protein is generated, due to the possibility of posttranscriptional regulation.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1179, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "18d8f9e4-b58a-451f-b0a0-912fcb141bb6": {"__data__": {"id_": "18d8f9e4-b58a-451f-b0a0-912fcb141bb6", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.5, para 5](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c2c96dc4-f24a-4163-8876-1bc856495b00", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.5, para 5](https://elifesciences.org/articles/95402)"}, "hash": "9025f951dd722712a6a21e20de7da84dd64042499fa041eace5d5717a480d636", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Hence, to consolidate and further improve neurotransmitter identity assignment throughout the entire C. elegans nervous system, and to circumvent potential limitations of multicopy, fosmid-based reporter transgenes on which previous neurotransmitter assignments have been based, we engineered and examined expression patterns of 16 knock-in reporter alleles of the 15 neurotransmitter synthesis, vesicular transport, and uptake loci listed above (Figure 1, Figure 2). For unc-17 and eat-4, we knocked-in a t2a::gfp::h2b (his-44) cassette right before the stop codon of the respective gene. For unc-25, we created two knock-in alleles with the t2a::gfp::h2b (his-44) cassette tagging isoforms a.1/c.1 and b.1 separately. For tdc-1, a gfp::h2b::t2a cassette was knocked into the N-terminus of the locus because of different C-terminal splice variants. The self-cleaving T2A peptide frees up GFP::H2B, which will be transported to the nucleus, thereby facilitating cell identification. For unc-46, unc-47, tph-1, bas-1, tbh-1, cat-1, cat-2, snf-3, and oct-1, we knocked-in a sl2::gfp::h2b cassette at the C-terminus of the locus. The SL2 sequence also provides for the separate production of GFP::H2B. Both types of reporter cassettes should capture posttranscriptional, 3'UTR-mediated regulation of each locus, e.g., by miRNAs and RNA-binding proteins (not captured by CeNGEN scRNA data). Since in each case the reporter is targeted to the nucleus, this strategy circumvents shortcomings associated with interpreting antibody staining patterns or dealing with too densely packed cytosolic signals. For mod-5, we analyzed a previously generated, non-nuclear reporter allele (Maicas et al., 2021). For all our neuronal cell identification, we utilized the neuronal landmark strain NeuroPAL (Tekieli et al., 2021; Yemini et al., 2021). The results of our neuronal expression pattern analysis are summarized in Figure 3 and detailed in Supplementary files 2 and 3. In the ensuing sections we describe these patterns in detail.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2020, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b34782db-65ca-4c62-88a7-4bf38fd823f8": {"__data__": {"id_": "b34782db-65ca-4c62-88a7-4bf38fd823f8", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.6, para 0](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d949cfb5-6a94-4753-8e3d-245cbd1539fa", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.6, para 0](https://elifesciences.org/articles/95402)"}, "hash": "4e558ce78ad3ac625743fb6930bbfd6d6d732bb35d5faf3c819f530383439557", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# eLife Tools and resources", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 27, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6cae77f2-74d4-4518-a9ab-cfb87cea0f70": {"__data__": {"id_": "6cae77f2-74d4-4518-a9ab-cfb87cea0f70", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.6, para 2](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3f55a386-ee0e-44e8-b924-9e669509752d", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.6, para 2](https://elifesciences.org/articles/95402)"}, "hash": "2551a67aefcf8d0fef470d9e4b7dab29849397898134a1a290110c58ccf51cac", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Figure 2. Schematics of reporter knock-in alleles. Reporter alleles were generated by CRISPR/Cas9 genome engineering. The SL2- or T2A-based separation of the reporter from the coding sequence of the respective loci enables targeting of the reporter to the nucleus (via the H2B tag), which in turn facilitates the identification of the cell expressing a given reporter. Genome schematics are from WormBase (Davis et al., 2022). See Figure 1\u2014figure supplement 1 for hdl-1 reporter alleles.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 487, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "51953280-91ce-44b2-b72a-9229c9d6f6cf": {"__data__": {"id_": "51953280-91ce-44b2-b72a-9229c9d6f6cf", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.7, para 0](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "64ca78b9-39ab-453f-9de2-e8ae2801e037", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.7, para 0](https://elifesciences.org/articles/95402)"}, "hash": "d75ad0d05ca3fb4f8e0e4700ceec0ccda45a749af818bf176d8028d6904aa9d2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# eLife Tools and resources", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 27, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "88362b2b-3576-4c09-89de-a5a415d6cb23": {"__data__": {"id_": "88362b2b-3576-4c09-89de-a5a415d6cb23", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.7, para 2](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3290bd24-f278-4629-abbd-ffefeadb8238", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.7, para 2](https://elifesciences.org/articles/95402)"}, "hash": "2a549e504e38afc29d9797e13bba908b80589a2ade9de6fa000fb05c873c1511", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## A", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6bd02f3d-21e2-44a5-bbb2-ef8a8e319d2e": {"__data__": {"id_": "6bd02f3d-21e2-44a5-bbb2-ef8a8e319d2e", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.7, para 3](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d6a9ee66-b8dc-48e4-b01f-9b00220f2cc6", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.7, para 3](https://elifesciences.org/articles/95402)"}, "hash": "1af7a44a5d828f8eb459d117772c0bae03e57590a6ee46321d8b215e893310fc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### HERMAPHRODITE", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 17, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ff9e9f4e-af7f-41f8-aa2d-a713db364fcf": {"__data__": {"id_": "ff9e9f4e-af7f-41f8-aa2d-a713db364fcf", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.7, para 4](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "72588e89-bec2-4eaa-8cf4-5b1d09512fab", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.7, para 4](https://elifesciences.org/articles/95402)"}, "hash": "4d623d7194140eab026ca54c89962e7f220574f79dcb96d454224bdce0cbd9fe", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|CLASS|NEURON|NEUROTRANSMITTER(S)|\n|-|-|-|\n|ADA|ADAL/R|Glu|\n|ADE|ADEL/R|DA|\n|ADF|ADFL/R|ACh 5-HT (syn + up)|\n|ADL|ADLL/R|Glu|\n|AFD|AFDL/R|Glu ACh|\n|AIA|AIAL/R|ACh|\n|AIB|AIBL/R|Glu betaine (up)|\n|AIM|AIML/R|Glu 5-HT (up)|\n|AIN|AINL/R|ACh|\n|AIY|AIYL/R|ACh|\n|AIZ|AIZL/R|Glu|\n|ALA|ALA/R|GABA|\n|ALM|ALML/R|Glu|\n|ALN|ALNL/R|ACh|\n|AQR|AQR|Glu|\n|AS|AS1-AS11|ACh|\n|ASE|ASEL/R|Glu|\n|ASG|ASGL/R|Glu \\*betaine (up)|\n|ASH|ASHL/R|Glu|\n|ASI|ASIL/R|\\*betaine (up)|\n|ASJ|ASJL/R|ACh|\n|ASK|ASKL/R|Glu|\n|AUA|AUAL/R|Glu betaine (up)|\n|AVA|AVAL/R|ACh|\n|AVB|AVBL/R|ACh|\n|AVD|AVDL/R|ACh|\n|AVE|AVEL/R|ACh|\n|AVF|AVFL/R|GABA (up)|\n|AVG|AVG|\\*ACh|\n|AVH|AVHL/R|orphan|\n|AVJ|AVJL/R|\\*GABA|\n|AVK|AVKL/R|orphan, unc-47 (+)|\n|AVL|AVL|GABA unknown MA?|\n|AVM|AVM|Glu|\n|AWA|AWAL/R|\\*ACh|\n|AWB|AWBL/R|ACh|\n|AWC|AWCL/R|Glu|\n|BAG|BAGL/R|Glu|\n|BDU|BDUL/R|orphan|\n|CAN|CANL/R|betaine (up)|\n|CEP|CEPDL/DR/VL/VR|DA|\n|DA|DA1-DA8|ACh|\n|DA9|DA9|ACh \\*betaine (up)|\n|DB|DB1-DB7|ACh|\n|DD|DD1-DD6|GABA|\n|DVA|DVA|ACh Glu|\n|DVB|DVB|GABA \\*betaine (up)|\n|DVC|DVC|Glu|\n|FLP|FLPL/R|Glu|\n|HSN|HSNL/R|ACh 5-HT|\n|I1|I1L/R|ACh|\n|I2|I2L/R|Glu|\n|I3|I3|ACh|\n|I4|I4|\\*Glu 5-HT (alt syn/up mechanism)|\n|I5|I5|Glu|\n|I6|I6|orphan, unc-47 (+)|\n|IL1|IL1DL/DR/L/R/VL/VR|Glu|\n|IL2|IL2DL/DR/L/R/VL/VR|ACh unknown MA?|\n|LUA|LUAL/R|Glu|\n### CLASS | NEURON | NEUROTRANSMITTER(S)\n---|---|---\nM1 | M1 | ACh\nM2 | M2L/R | ACh\nM3 | M3L/R | Glu *betaine (up)\nM4 | M4 | ACh\nM5 | M5 | ACh Glu\nMC | MCL/R | ACh\nMI | MI | Glu 5-HTP\nNSM | NSML/R | 5-HT *betaine (up)\nOLL | OLLL/R | Glu\nOLQ | OLQDL/DR/VL/VR | Glu\nPDA | PDA | ACh *betaine (up)\nPDB | PDB | ACh\nPDE | PDEL/R | DA Glu\nPHA | PHAL/R | *Glu\nPHB | PHBL/R | Glu\nPHC | PHCL/R | Glu betaine (up)\nPLM | PLML/R | Glu\nPLN | PLNL/R | ACh\nPQR | PQR | Glu\nPVC | PVCL/R | ACh\nPVD | PVDL/R | Glu\nPVM | PVM | orphan\nPVN | PVNL/R | ACh Glu betaine (up)\nPVP | PVPL/R | ACh\nPVQ | PVQL/R | orphan\nPVR | PVR | Glu\nPVT | PVT | orphan, unc-47 (+) orphan, unc-46 (+)\nPVW | PVWL/R | orphan, unc-47 (+) orphan, unc-46 (+)\nRIA | RIAL/R | Glu\nRIB | RIBL/R | GABA\nRIC | RICL/R | octopamine Glu\nRID | RID | orphan, unc-47 (+)\nRIF | RIFL/R | ACh\nRIG | RIGL/R | Glu\nRIH | RIH | ACh 5-HT (up)\nRIM | RIML/R | Glu tyramine (syn + up) betaine (up)\nRIP | RIPL/R | ACh\nRIR | RIR | ACh *betaine (up)\nRIS | RIS | GABA betaine (up)\nRIV | RIVL/R | ACh\nRMD | RMDDL/DR/L/R/VL/VR | ACh\nRME | RMED/L/R/V | GABA\nRMF | RMFL/R | ACh\nRMG | RMGL/R | orphan\nRMH | RMHL/R | ACh *betaine (up)\nSAA | SAADL/DR/VL/VR | ACh\nSAB | SABD/VL/VR | ACh\nSDQ | SDQL/R | ACh\nSIA | SIADL/DR/VL/VR | ACh\nSIB | SIBDL/DR/VL/VR | ACh\nSMB | SMBDL/DR/VL/VR | ACh\nSMD | SMDDL/DR/VL/VR | ACh *GABA *betaine (up)\nURA | URADL/DR/VL/VR | ACh\nURB | URBL/R | ACh bas-1-depen MA?\nURX | URXL/R | ACh *5-HT (up) *betaine (up)\nURY | URYDL/DR/VL/VR | Glu\nVA | VA1-VA11 | ACh\nVA12 | VA12 | ACh *betaine (up)\nVB | VB1-VB11 | ACh *betaine (up)\nVC | VC1-VC3, VC6 | ACh 5-HT (alt syn/up mechanism)\nVC4, VC5 | VC4, VC5 | ACh\nVD | VD1-VD13 | GABA", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2932, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c9bb5627-8f46-451b-b1e1-c328c212410e": {"__data__": {"id_": "c9bb5627-8f46-451b-b1e1-c328c212410e", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.7, para 5](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "99ffc6ff-8268-4f00-9e53-583f3b6aff1f", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.7, para 5](https://elifesciences.org/articles/95402)"}, "hash": "ebc1eeba91667c1677391458f5508092bada3a95cba8306c31eca374a1c0bc15", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### MALE-SPECIFIC NEURONS", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 25, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f86853dd-b01f-4583-9440-43dceffa628c": {"__data__": {"id_": "f86853dd-b01f-4583-9440-43dceffa628c", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.7, para 6](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d2d04149-c66d-435d-83b4-1a6f5c7b944c", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.7, para 6](https://elifesciences.org/articles/95402)"}, "hash": "0d255d3b6196e11b7b27c5abe6d3e168a7def8af626c9c5a8de853e272c4e112", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|CLASS|NEURON|NEUROTRANSMITTER(S)|\n|-|-|-|\n|CEM|CEMDLDR/VL/VR|ACh 5-HTP unknown MA?|\n|MCM|MCML/R|orphan, unc-47 (+)|\n|CA|CA1-CA4|ACh \\*Glu|\n||CA5, CA6, CA8, CA9|ACh|\n||CA7|ACh Glu|\n|CP|CP0|Glu|\n||CP1-CP4|ACh 5-HT (syn + up)|\n||CP5, CP6|Glu 5-HT (syn + up)|\n||CP7, CP8|ACh|\n|CP9|CP9|GABA|\n|DVE|DVE|\\*bas-1-depen MA?|\n|DVF|DVF|\\*bas-1-depen MA?|\n|DX|DX1/2|ACh|\n|EF|EF1/2|GABA|\n|HOA|HOA|Glu tyramine bas-1-depen MA?|\n|HOB|HOB|ACh unknown MA?|\n|PDC|PDC|ACh betaine (up)|\n|PGA|PGA|ACh 5-HT (up)|\n|PVV|PVV|ACh Glu \\*betaine (up)|\n|PVY|PVY|ACh unknown MA?|\n|PVX|PVX|ACh unknown MA?|\n|PVZ|PVZ|ACh|\n|DX|DX3/4|ACh|\n|EF|EF3/4|GABA|\n|RnA|R1AL/R|ACh|\n||R2AL/R|ACh GABA bas-1-depen MA?|\n||R3AL/R|ACh bas-1-depen MA?|\n||R4AL/R|ACh|\n||R5AL/R|Glu DA|\n||R6AL/R|ACh GABA bas-1-depen MA?|\n||R7AL/R|DA tyramine|\n||R8AL/R|ACh tyramine bas-1-depen MA?|\n||R9AL/R|Glu DA|\n|RnB|R1BL/R|ACh 5-HT PEOH?|\n||R2BL/R|Glu PEOH?|\n||R3BL/R|5-HT PEOH?|\n||R4BL/R|ACh \\*5-HT PEOH?|\n||R5BL/R|ACh unknown MA?|\n||R6BL/R|Glu \\*bas-1-depen MA?|\n||R7BL/R|\\*ACh \\*5-HT PEOH?|\n||R8BL/R|ACh octopamine|\n||R9BL/R|\\*ACh GABA 5-HTP & 5-HT (up)|\n|PHD|PHDL/R|ACh betaine (up)|\n|PCA|PCAL/R|Glu|\n|PCB|PCBL/R|ACh bas-1-depen MA?|\n|PCC|PCCL/R|ACh|\n|SPC|SPCL/R|ACh bas-1-depen MA?|\n|SPD|SPDL/R|orphan|\n|SPV|SPVL/R|ACh|\n> See Supplementary Files 2 & 3 and Tables 1 & 2 for gene expression details, neurotransmitter assignment rationale, and updates in this paper compared to prior studies. See Supplementary File 4 for sexually dimorphic expression of reporter alleles in sex-shared neurons.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1532, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b156b4fc-3cce-47cb-bfc3-c98c4945952a": {"__data__": {"id_": "b156b4fc-3cce-47cb-bfc3-c98c4945952a", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.7, para 7](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5e436a42-46ce-4086-bfb2-ec6bfef1b7e7", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.7, para 7](https://elifesciences.org/articles/95402)"}, "hash": "73fa7bb72d96a881f22133d2569e514faa6ba2c97a874f1c9edf322ce60b9c76", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "When neurotransmitter is marked with \\*: potential neurotransmitter usage is predicted based on variable expression of given gene(s).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 133, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3886cfc6-6779-419e-974b-b5f555e072be": {"__data__": {"id_": "3886cfc6-6779-419e-974b-b5f555e072be", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.7, para 8](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0f8c69fe-1096-42aa-9f94-80d9af2c0d42", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.7, para 8](https://elifesciences.org/articles/95402)"}, "hash": "4ddf84d4117fbde34ab0a466bc0295f84f1d13bf33af68c673d0f44c91a81de5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## B", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ee891400-3b90-4d19-a76f-f0ffdf20fd20": {"__data__": {"id_": "ee891400-3b90-4d19-a76f-f0ffdf20fd20", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.7, para 9](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f985d5d7-a241-4b56-9963-5804d2c932ff", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.7, para 9](https://elifesciences.org/articles/95402)"}, "hash": "0c1537ca0e2832c95e35a45703629853668586707cc3c5405daf2c2bbd169c53", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Figure 3. Summary of neurotransmitter usage and atlases. See Table 1, Table 2, and Supplementary files 2\u20134 for individual gene expression, rationale for neurotransmitter assignments, and more detailed notes. (A) ACh=acetylcholine; Glu=glutamate; GABA=\u03b3-aminobutyric acid; DA=dopamine; 5-HT=5-hydroxytryptamine, or serotonin; 5-HTP=5-hydroxytryptophan; PEOH?=the neuron has the potential to use \u03b2-hydroxyphenethylamine, or phenylethanolamine; bas-1-depen MA?=the neuron has the potential to use bas-1-dependent unknown monoamines (histamine, tryptamine,", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 552, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "827def28-b6fb-4f9f-955a-69a579018ee4": {"__data__": {"id_": "827def28-b6fb-4f9f-955a-69a579018ee4", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.8, para 1](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "146df9d1-7d0e-4d90-a4ec-3ffb084cd495", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.8, para 1](https://elifesciences.org/articles/95402)"}, "hash": "a0c1ed0b2ba45243c4b24321fe7f6e8fedbce9913d3732cdb99f1963f7eb2d2d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Figure 3 continued\nphenylethylamine \\[PEA]; also see Figure 1\u2014figure supplement 1); unknown MA?=the neuron has the potential to use non-canonical monoamines; (up)=neurotransmitter uptake; (syn)=neurotransmitter synthesis; \\*=dim and variable expression of respective identity gene(s) is detected. Variability could be due to one of the following reasons: (1) the endogenous gene is indeed expressed in some but not all animals; (2) the endogenous gene is indeed expressed in every animal but the level of reporter expression is below detection threshold in some. Variability is detected only at low fluorescent intensity; at higher intensities, expression remains consistent. Results for anti-\u03b3-aminobutyric acid (GABA) staining in SMD and anti-serotonin staining in VC4, VC5, CEM, I5, and URX are variable based on previous reports (see text for citations). (B) Information from (A) shown in the context of neuron positions in worm schematics. Note 'unknown monoamine' here includes both 'bas-1-depen MA' and 'unknown MA' in (A). Neurons marked with 'u' can uptake given neurotransmitters but not exclusively; some may also synthesize them, e.g., ADF can both synthesize and uptake serotonin.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1193, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "07f67426-a46e-4813-8495-f09140d04861": {"__data__": {"id_": "07f67426-a46e-4813-8495-f09140d04861", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.8, para 2](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5b99f9cd-0029-4426-8e2a-e66f6d98ec04", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.8, para 2](https://elifesciences.org/articles/95402)"}, "hash": "f8dd2f4646046d90a4e1d6b952727b5ca30ea281af326f9ee7dc9d75d3a2e1d3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Expression of a reporter allele of eat-4/VGLUT, a marker for glutamatergic identity, in the hermaphrodite", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 108, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4c51207c-87b0-4e32-b013-af84fff762e6": {"__data__": {"id_": "4c51207c-87b0-4e32-b013-af84fff762e6", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.8, para 3](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "710bc872-a74c-4709-a62e-15400b4d235b", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.8, para 3](https://elifesciences.org/articles/95402)"}, "hash": "3934386804a1b23afbbbaeee7de4086fd7a5468ea4e863b6cbb3fe042840ddff", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "37 of the 38 previously reported neuron classes that express an eat-4 fosmid-based reporter (Serrano-Saiz et al., 2013) showed eat-4 transcripts in the CeNGEN scRNA atlas (Taylor et al., 2021) at all four thresholds of stringency, and 1/38 (PVD neuron) showed it in three out of the four threshold levels (Figure 1B, Supplementary file 1). However, scRNA transcripts were detected at all four threshold levels in three additional neuron classes, RIC, PVN, and DVA, for which no previous reporter data provided support. In a recent publication, we had already described that the eat-4 reporter allele syb4257 is expressed in RIC (Reilly et al., 2022) (confirmed in Figure 4A). We now also confirm expression of this reporter allele, albeit at low levels, in DVA and PVN (Figure 4B, Supplementary file 2).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 803, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "380104ba-a08c-4fbf-aab2-21a7e40ba1af": {"__data__": {"id_": "380104ba-a08c-4fbf-aab2-21a7e40ba1af", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.8, para 4](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9d51b896-4c9f-4d91-8423-77c115fe417f", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.8, para 4](https://elifesciences.org/articles/95402)"}, "hash": "07ea315ea7906536f60ccd236fe481fc3b5e7541cbbbe0c3362a68c112ebbc22", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Another neuron found to have some eat-4 transcripts, but only with the two lower threshold sets, is the I6 pharyngeal neuron. Consistent with our previous fosmid-based reporter data, we detected no I6 expression with our eat-4(syb4257) reporter allele. The eat-4 reporter allele also shows expression in the pharyngeal neuron M5, albeit very weakly (Figure 4A, Supplementary file 2), consistent with CeNGEN scRNA data. Weak expression of the eat-4 fosmid-based reporter in ASK and ADL remained weak, but clearly detectable with the eat-4(syb4257) reporter allele (Figure 4A, Supplementary file 2). Extremely dim expression in PHA can be occasionally detected. Whereas the PVQ neuron class displays eat-4 scRNA transcripts and was reported to show very dim eat-4 fosmid-based reporter expression, we detected no expression of the eat-4(syb4257) reporter allele in PVQ neurons (Figure 4B, Supplementary file 2). We also did not detect expression of eat-4(syb4257) in the GABAergic AVL and DVB neurons, in which a recent report describes expression of an eat-4 promoter fusion reporter (Li et al., 2023). An absence of eat-4(syb4257) expression in AVL and DVB is also consistent with the absence of scRNA transcripts in these neurons.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1231, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2c832089-a5e0-43ce-84d5-1a7990fd720c": {"__data__": {"id_": "2c832089-a5e0-43ce-84d5-1a7990fd720c", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.8, para 5](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a0296aad-fb45-42d5-a947-da2c272425e5", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.8, para 5](https://elifesciences.org/articles/95402)"}, "hash": "13490a70f4875aeb04ca6f090e4a889bc9756562c8b322c4f5e85aafdf1e299c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "A few neurons were found to express eat-4 transcripts by the CeNGEN atlas, but only with lower threshold levels, including, for example, the RMD, PVM, and I4 neurons (Figure 1B, Supplementary file 1). We failed to detect reporter allele expression in RMD or PVM neurons, but occasionally observed very dim expression in I4. Lastly, we identified a novel site of eat-4 expression in the dopaminergic PDE neuron (Figure 4B, Supplementary file 2). While such expression was neither detected with previous reporters nor scRNA transcripts, we detected it very consistently but at relatively low levels.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 597, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c2e58590-2b5a-4178-ac8a-727a6bd93b9d": {"__data__": {"id_": "c2e58590-2b5a-4178-ac8a-727a6bd93b9d", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.8, para 6](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3f3a0aac-73fa-4231-8322-7a588bcde11c", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.8, para 6](https://elifesciences.org/articles/95402)"}, "hash": "10e08fcee7764ec8597f07d6628c8c639a0ea4d490ebaa7f3ecbf177505daecb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Expression of a reporter allele of unc-17/VAChT, a marker for cholinergic identity, in the hermaphrodite", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 107, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e6544fef-7c3e-43ce-954b-f7e5e2e0ab4b": {"__data__": {"id_": "e6544fef-7c3e-43ce-954b-f7e5e2e0ab4b", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.8, para 7](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c7a7424d-8c66-4448-8d93-99efa13f070a", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.8, para 7](https://elifesciences.org/articles/95402)"}, "hash": "2a824b15e0383c383b0a308a29070b9af962d59dc6ce3699fc163b88debec82a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "41 of previously described 52 neuron classes that show unc-17 fosmid-based reporter expression (Pereira et al., 2015) showed transcripts in the CeNGEN scRNA atlas at four out of four threshold levels, another seven neuron classes at three out of four threshold levels, and one at the lowest two threshold levels (Taylor et al., 2021). Only one neuron class, RIP, displayed scRNA levels at all four thresholds, but showed no corresponding unc-17 fosmid-based reporter expression (Figure 1B, Supplementary file 1). Using the unc-17(syb4491) reporter allele (Figure 1A), we confirmed expression in RIP (Figure 4C, Supplementary file 2). Of the additional neuron classes that show unc-17 expression at the lower stringency transcript detection levels (Figure 1B, Supplementary file 1), we were able to detect unc-17 reporter allele expression only in AWA (Figure 4C, Supplementary file 2). Conversely, a few neurons display weak expression with previous multicopy, fosmid-based reporter constructs (RIB, AVG, PVN) (Pereira et al., 2015), but show no CeNGEN scRNA support for such", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1075, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "883e9960-7670-4273-af74-08f9f0bc6e56": {"__data__": {"id_": "883e9960-7670-4273-af74-08f9f0bc6e56", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.9, para 1](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "165d2085-ad24-4661-95bb-a4eee0367aaa", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.9, para 1](https://elifesciences.org/articles/95402)"}, "hash": "175333fe22e81614dbc68edb8843aa42667354c1af6909f9e4ae5f192d43af3d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# eat-4(syb4257\\[eat-4::t2a::gfp::h2b]) III", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 43, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9b96d608-1767-47f7-9a2b-3f30d1b27109": {"__data__": {"id_": "9b96d608-1767-47f7-9a2b-3f30d1b27109", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.9, para 2](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "52132fe9-c957-491c-a5ba-a23f27282e1e", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.9, para 2](https://elifesciences.org/articles/95402)"}, "hash": "3a259310a010905d0f86ff3ab4032bb7ac189fb1a415efe91bc4b9dddd936f83", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## A", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "add78114-f73a-487a-b5ac-2afcb2fae081": {"__data__": {"id_": "add78114-f73a-487a-b5ac-2afcb2fae081", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.9, para 3](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4cf74783-b6ab-429b-b506-fbb20a165b86", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.9, para 3](https://elifesciences.org/articles/95402)"}, "hash": "6d77878d100246875aa389b8929fa940573012618d1d93f6407aec4f0221657b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* **eat-4**^CRISPR::gfp\n* NeuroPAL\n* MERGE\n* lateral view\n* ADL\n* M5\n* ASK\n* RIC", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 80, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2784687d-fc3c-4d04-b3ba-31f1610f6960": {"__data__": {"id_": "2784687d-fc3c-4d04-b3ba-31f1610f6960", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.9, para 4](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "386fb6d0-e999-4958-b7e9-e7caa59fc1fa", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.9, para 4](https://elifesciences.org/articles/95402)"}, "hash": "7802d17e1c0a905b5149b63be12e8d62685bdfa29eefe65a0c5502d2370ce169", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## B", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "397823e8-375b-4c58-82ea-a08547418ae5": {"__data__": {"id_": "397823e8-375b-4c58-82ea-a08547418ae5", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.9, para 5](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cba36ff6-6a2a-461e-8201-ea7db403ec53", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.9, para 5](https://elifesciences.org/articles/95402)"}, "hash": "ca871fbff96c98ad79f70d3fdf78eebb1547e89175ef027b5e2aae2ea07d7850", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* HERM MIDBODY\n* HERM TAIL\n* MALE TAIL\n* PDE\n* DVC\n* PVQ (-)\n* PVN\n* PVD\n* DVA\n* PHA(+/-)\n* PDE\n* DVC\n* PVQ\n* PVN\n* PVD\n* DVA\n* PHA\n* PDE\n* DVC\n* PVQ\n* PVN\n* PVD\n* DVA\n* PHA\n* **eat-4**^CRISPR::gfp\n* expression in PVN\n* GFP intensity (a.u.)\n* 2.0\n* 1.5\n* 1.0\n* 0.5\n* 0.0\n* herm\n* male", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 284, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "abac77b6-d81c-4ef8-8e6d-f2f1cf5b3296": {"__data__": {"id_": "abac77b6-d81c-4ef8-8e6d-f2f1cf5b3296", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.9, para 6](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "870bab64-6389-402c-afcd-68d4726675d8", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.9, para 6](https://elifesciences.org/articles/95402)"}, "hash": "164ca125f6ac2758e5bab900b8119c651bad5079e2325daeb1d722c225f8b986", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# unc-17(syb4491\\[unc-17::t2a::gfp::h2b]) IV", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 44, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5b63c0fa-2979-4e81-89f1-a7a666376a17": {"__data__": {"id_": "5b63c0fa-2979-4e81-89f1-a7a666376a17", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.9, para 7](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "51523ddc-deb6-4287-94d9-35952a899ae4", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.9, para 7](https://elifesciences.org/articles/95402)"}, "hash": "6e1298f5c7f6791c5c6144261c52915164c7e0b067811cc427e9b9da495ff1cd", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## C", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "30b17c68-77af-4a98-9511-d68de976b0dc": {"__data__": {"id_": "30b17c68-77af-4a98-9511-d68de976b0dc", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.9, para 8](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "74524570-627a-41c6-8a20-9ce947cf85d2", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.9, para 8](https://elifesciences.org/articles/95402)"}, "hash": "a79d352a82c56e6313d97d8119ce2dacc63b72260dd8e19619bcf188602493a0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* **unc-17**^CRISPR::gfp\n* NeuroPAL\n* MERGE\n* lateral view\n* AVJ(-)\n* AVJ\n* RIP\n* AWA(+/-)\n* AFD\n* RIB(-)\n* FLP(-)\n* AFD\n* RIB\n* FLP\n* AWA(+/-)\n* AVJ(-)\n* AFD\n* RIB(-)\n* FLP(-)\n* (+)\n* AIM\n* AIY\n* AVG\n* AIM\n* AIY\n* AVG\n* AIM\n* AIY\n* AVG\n* lateral view\n* AIM\n* AIY\n* AVG\n* AIM\n* AIY\n* AVG\n* AIM\n* AIY\n* AVG\n* lateral view", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 320, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1532b491-3fec-44e1-aceb-f22e11d81b91": {"__data__": {"id_": "1532b491-3fec-44e1-aceb-f22e11d81b91", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.9, para 9](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "239859d4-2629-4a1d-99fb-8945937dfbf1", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.9, para 9](https://elifesciences.org/articles/95402)"}, "hash": "5306c72c486a60b649ea33c52684d45613abd1b511d1db8150ceec8728ab6201", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## D", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "14e2d3f1-ebe4-4f49-906c-173b00531549": {"__data__": {"id_": "14e2d3f1-ebe4-4f49-906c-173b00531549", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.9, para 10](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d851b2ba-2e19-4ed3-9368-74e77baf6e86", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.9, para 10](https://elifesciences.org/articles/95402)"}, "hash": "49cecb03a04d274bf9587f87dc87017fc9ed5556a60da951eac42657adc7b3a3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* **unc-17**^CRISPR::gfp\n* NeuroPAL\n* MERGE\n* PVN\n* PVN\n* PVN\n* lateral view\n* PVN\n* PVN\n* PVN\n* lateral view", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 109, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "832d5425-beed-4c65-9e10-7da59768517a": {"__data__": {"id_": "832d5425-beed-4c65-9e10-7da59768517a", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.9, para 11](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b1f93fe5-927a-4c93-9fa8-ae0fd5a37638", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.9, para 11](https://elifesciences.org/articles/95402)"}, "hash": "8a3c7cde71e58e50799cf123c8713426be6a8d336fec200ef3c277781757a463", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Figure 4. Expression of eat-4/VGLUT and unc-17/VAChT reporter alleles in the adult hermaphrodite. Neuronal expression of eat-4(syb4257) and unc-17(syb4491) was characterized with landmark strain NeuroPAL (otIs696 and otIs669, respectively). Only selected neurons are shown for illustrating updates from previous reports. See *Supplementary file 2* for a complete list of neurons. (A) Dim expression of eat-4(syb4257) in head neurons\nFigure 4 continued on next page", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 464, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f7fed695-3eab-4932-9da4-7aa43e02cc61": {"__data__": {"id_": "f7fed695-3eab-4932-9da4-7aa43e02cc61", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.10, para 1](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cc94ab12-65fc-4579-9d8e-593b6a8b9843", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.10, para 1](https://elifesciences.org/articles/95402)"}, "hash": "93ef84bd8e54f78cda1ce85db9014196a7e1c21e94a64cb8de1e43ac6a44de47", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Figure 4 continued\nASK and ADL is consistent with previous fosmid-based reporter expression. RIC expression is consistent with previous observation using the same reporter allele (*Reilly et al., 2022*). In addition, dim expression is detected in pharyngeal neuron M5 (also in grayscale inset), previously not detected with eat-4 GFP fosmid-based reporter (otIs388) but visible with eat-4 mCherry fosmid-based reporter (otIs518). (B) Previously uncharacterized eat-4 expression in PDE and DVA neurons is detected with the eat-4(syb4257) reporter allele. Variable expression in PHA is also occasionally detected. No expression is detected in PVQ. Expression in PVN is detected in both sexes but at a much higher level in the male. (C) In the head, prominent expression of unc-17(syb4491) in RIP and dim expression in AWA and AFD neurons are detected. There is no visible expression in RIB, FLP, or AVJ. Consistent with previous reports, AIM expresses unc-17 only in males and not hermaphrodites. In addition, very dim expression of AVG can be detected occasionally in hermaphrodites (representative image showing an animal with no visible expression) and slightly stronger in males (representative image showing an animal with visible expression). Inset, grayscale image showing dim expression for AWA and AFD and no expression for RIB. (D) In the tail, PVN expresses unc-17(syb4491) in both sexes, consistent with previous reports. Scale bars, 10 \u00b5m in color images in A, C, and D; 5 \u00b5m in B and all grayscale images. Quantification in B is done by normalizing fluorescent intensity of eat-4 GFP to that of the blue channel in the NeuroPAL background. Statistics, Mann-Whitney test.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1682, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5ca6a5a2-0663-4765-b091-0a4990d9bb20": {"__data__": {"id_": "5ca6a5a2-0663-4765-b091-0a4990d9bb20", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.10, para 2](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "15fbd198-76a9-43a6-ba9e-555b842c10fa", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.10, para 2](https://elifesciences.org/articles/95402)"}, "hash": "72fb73249b92b6e4ba8f863945370df08761df2fb892a2d9201055e550e5fb2a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "expression (*Taylor et al., 2021*). The unc-17(syb4491) reporter allele confirmed weak but consistent expression in the PVN neurons as well as variable, borderline expression in AVG (Figure 4C and D). However, we failed to detect unc-17(syb4491) reporter allele expression in the RIB neurons.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 292, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "94ad6177-1291-4b0c-9140-5439c215ef3c": {"__data__": {"id_": "94ad6177-1291-4b0c-9140-5439c215ef3c", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.10, para 3](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "aa99c577-2a7e-46d7-bac2-5ebde408ec4d", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.10, para 3](https://elifesciences.org/articles/95402)"}, "hash": "9d67fa52710e443c9c1ec60bc8ab24f2d431745e91e53eef6d15850f882dd3f4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We detected another novel site of unc-17 expression, albeit dim, in the glutamatergic AFD neurons (Figure 4C, Supplementary file 2). This expression was not reported with previous fosmid-based reporter or CeNGEN scRNA data. Consistent with AFD and PVN being potentially cholinergic, scRNA transcript reads for cha-1/ChAT, the ACh-synthesizing choline acetyltransferase, were also detected in AFD and PVN (Supplementary file 1).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 427, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9ed91ef0-2a5b-4d65-8f01-33c114099e05": {"__data__": {"id_": "9ed91ef0-2a5b-4d65-8f01-33c114099e05", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.10, para 4](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0fd0b716-573e-4c98-8639-2ddfe85d8284", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.10, para 4](https://elifesciences.org/articles/95402)"}, "hash": "593702050cabe847ccd4d71e423f98bac2272521a07136c3a4e78d871c13e89b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Lastly, another notable observation is the lack of any unc-17 reporter expression or CeNGEN scRNA transcripts in the interneuron AVJ, but presence of CeNGEN scRNA transcript reads for cha-1/ChAT (Supplementary file 1), which shares exons with the unc-17/VAChT locus (*Alfonso et al., 1994*). Although no reporter data is available for cha-1/ChAT, such interesting mismatch between available unc-17 and cha-1/ChAT expression data could provide a hint to potential non-vesicular cholinergic transmission in the AVJ neurons in *C. elegans*, potentially akin to reportedly non-vesicular release of acetylcholine in the visual system of *Drosophila* (*Yang and Kunes, 2004*).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 670, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7a5df09a-11ee-4f1e-9f60-f96e7713bbec": {"__data__": {"id_": "7a5df09a-11ee-4f1e-9f60-f96e7713bbec", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.10, para 5](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0982db83-fe16-4fcc-b8f3-89e42c562bf5", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.10, para 5](https://elifesciences.org/articles/95402)"}, "hash": "28a743504ae1fed8a65b530e983fa418df467660dde22e0fadf6a8c0275c494d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Expression of reporter alleles for GABAergic pathway genes in the hermaphrodite", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 82, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1c5de984-739b-483a-9f85-e0010f83b67c": {"__data__": {"id_": "1c5de984-739b-483a-9f85-e0010f83b67c", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.10, para 6](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9df3610a-a51d-4565-ab51-568a4086377e", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.10, para 6](https://elifesciences.org/articles/95402)"}, "hash": "24fb2a1beef276a2845fb99fe550091a21cd55bfdab66c43f30c9d201eec25a6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Expression of unc-25/GAD", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 28, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cee1e72f-6135-45e6-a5aa-0a482aecbe58": {"__data__": {"id_": "cee1e72f-6135-45e6-a5aa-0a482aecbe58", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.10, para 7](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "28cda358-2b80-4c23-8fa7-4af3bd7e020c", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.10, para 7](https://elifesciences.org/articles/95402)"}, "hash": "c94eb2df539f5feec825423e15f33f1edef69bd61df03ba3a6aa8621b1020133", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The most recent analysis of GABAergic neurons identified GABA-synthesizing cells by anti-GABA staining and an SL2-based unc-25/GAD reporter allele that monitors expression of the rate-limiting step of GABA synthesis, generated by CRISPR/Cas9 engineering (*Gendrel et al., 2016*). The CeNGEN scRNA atlas shows robust support for these assignments at all four threshold levels (Figure 1B, Supplementary file 1). unc-25 scRNA signals (but no reporter signals) were detected at several orders of magnitude lower levels in three additional neuron classes (AWA, AVH, PVT), but only with the least robust threshold level.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 614, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ebc2aac6-5ff8-4cd3-b0e5-879cc8b9a553": {"__data__": {"id_": "ebc2aac6-5ff8-4cd3-b0e5-879cc8b9a553", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.10, para 8](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "59242abf-2a46-4be1-88fa-1f9f76ecd099", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.10, para 8](https://elifesciences.org/articles/95402)"}, "hash": "eb83895373da02c2bef05e577a9f5f07bf928dce2627e522ee00de54e06ecc86", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In this study we generated another unc-25/GAD reporter allele, using a t2a::gfp::h2b cassette (ot1372) (Figure 2). This allele showed the same expression pattern as the previously described SL2-based unc-25(ot867) reporter allele (Figure 5A, Supplementary file 2). This includes a lack of expression in a number of neurons that stain with anti-GABA antibodies (SMD, AVA, AVB, AVJ, ALA, and AVF) and GLR glia, corroborating the notion that these neurons and glia take up GABA from other cells (indeed, a subset of those cells do express the GABA uptake reporter SNF-11; *Gendrel et al., 2016*).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 593, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1ed4b9e5-1834-4f17-97f3-3c35e6e559d9": {"__data__": {"id_": "1ed4b9e5-1834-4f17-97f3-3c35e6e559d9", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.10, para 9](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "928f0779-d48d-4579-b1eb-518c5a4c3718", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.10, para 9](https://elifesciences.org/articles/95402)"}, "hash": "67d4725e786242742fa2932b9454d5675650a5bdde9855e60401850454389640", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We carefully examined potential unc-25/GAD reporter allele expression in the AMsh glia, which were reported to generate GABA through unc-25/GAD (*Duan et al., 2020; Fernandez-Abascal et al., 2022*). We did not detect visible unc-25(ot867) or unc-25(ot1372) reporter allele expression in AMsh, consistent with the failure to directly detect GABA in AMsh through highly sensitive anti-GABA staining (*Gendrel et al., 2016*). Since these reporters do not capture an alternatively spliced isoform b.1 (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 498, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "94fff2c5-86fa-4897-ac7a-6fe04264adb6": {"__data__": {"id_": "94fff2c5-86fa-4897-ac7a-6fe04264adb6", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.10, para 10](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2b8cdab6-8b32-48c0-8b00-07cdb4de082a", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.10, para 10](https://elifesciences.org/articles/95402)"}, "hash": "2c868ee3e28a21690a86c53a7e54ce439c0facc81d8ba292f77b4be9a4f95d1b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "), we generated another reporter allele, unc-25(ot1536), to specifically", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 72, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "08ec6369-fea2-486c-9f7f-1dd5a1ea2e51": {"__data__": {"id_": "08ec6369-fea2-486c-9f7f-1dd5a1ea2e51", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.11, para 1](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "114ec5a5-76a3-49c0-9254-4d56def8dc0a", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.11, para 1](https://elifesciences.org/articles/95402)"}, "hash": "28c2b3e4b41581587b1abca65336648f0d76a29bded542ddfae1dbef1a9e038a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# A", "mimetype": 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{"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.11, para 31](https://elifesciences.org/articles/95402)"}, "hash": "19587a1b068cbafdb92bdbed319c276112bcb9c0f1c0eb0db14c187306e73474", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Figure 5. Expression of GABA pathway genes in the adult hermaphrodite. (A) Expression of the unc-25/GAD reporter allele ot1372 is detected in the head, ventral nerve cord, and tail neurons. The expression pattern of this new T2A-based reporter allele is similar to that of a previously described SL2-based reporter allele, unc-25(ot867) (Gendrel et al., 2016). (B) Expression of unc-47/VGAT reporter allele syb7566. Left, the expression pattern of the reporter allele largely matches that of a previously described unc-47 mCherry fosmid-based reporter (otIs564) in the head. Right, a close-up view for the Figure 5 continued on next page", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 637, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "14cb93d8-b9a3-4f5d-8295-9949b5cebff5": {"__data__": {"id_": "14cb93d8-b9a3-4f5d-8295-9949b5cebff5", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.12, para 0](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "010c3772-1034-44e9-9888-77beb6f44f66", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.12, para 0](https://elifesciences.org/articles/95402)"}, "hash": "653a09c0bd76dd6503b0b78939c1854448bcd2de56655737dea4fda1024c6b19", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# eLife Tools and resources", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 27, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9224bf21-d01c-4164-8924-860c36698a8f": {"__data__": {"id_": "9224bf21-d01c-4164-8924-860c36698a8f", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.12, para 3](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bd51c5e6-d96b-421f-ac07-3322e4c1d288", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.12, para 3](https://elifesciences.org/articles/95402)"}, "hash": "bbc561c81c5aa5a75e991a72c5a0107bc12128b114e5589881eadce1c272e6c1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "characterization of the reporter allele expression with landmark strain NeuroPAL (otIs669). In the head, consistent with previous reports of the unc-47 fosmid-based reporter (otIs564), dim expression of unc-47(syb7566) in SMD, ALA, and very dim and variable expression in IL1 is detected in both sexes, and unc-47(syb7566) is expressed in ADF only in the male and not hermaphrodite. In addition, the reporter allele is also expressed at a very dim level in the pharyngeal neuron I1 (also in inset) whereas no expression is detected in M1. In the tail, consistent with previous reports of the fosmid, sexually dimorphic expression of the unc-47(syb7566) reporter allele is also detected in PDB, AS11, PVN, and PHC only in the male and not the hermaphrodite. In addition, we also detected very dim expression of PLM in both sexes, confirming potential dim expression of the unc-47 mCherry fosmid-based reporter that was only readily visible after anti-mCherry staining in the past (Serrano-Saiz et al., 2017b). Scale bars, 5 \u00b5m for insets and 10 \u00b5m for all other images. (C) Expression of unc-46/LAMP reporter allele syb7278 is largely similar to that of the previously described unc-46/LAMP mCherry fosmid-based reporter (otIs568). We also observed expression of both the reporter allele and fosmid-based reporter in PVW, PVN, and very dimly in PDA. Scale bars, 10 \u00b5m.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1367, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6fd9c4e9-386e-4405-9c18-777325ce2093": {"__data__": {"id_": "6fd9c4e9-386e-4405-9c18-777325ce2093", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.12, para 4](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5f820c2d-8160-45ff-8a44-8b05ea6833ea", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.12, para 4](https://elifesciences.org/articles/95402)"}, "hash": "229e86bf1618a5d32bc35d5618be9e51becd86573525e7c515e9115704f583c7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "target this isoform. However, we did not observe any discernible fluorescent reporter expression from this allele. Hence, it is unlikely that an alternative isoform could contribute to expression in additional cell types.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 221, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a89d82fd-0135-4d52-ae62-9b78f06cfaae": {"__data__": {"id_": "a89d82fd-0135-4d52-ae62-9b78f06cfaae", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.12, para 5](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3cc2d531-f4e0-460b-ac25-f22b8e5434e2", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.12, para 5](https://elifesciences.org/articles/95402)"}, "hash": "7a8eabc1d7aeb86efc3863f61935c2235f3fc7f45e979a57ab4a866874b14dc9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Expression of unc-47/VGAT", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 28, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "addff3b7-5011-43aa-a7b2-faa05f5b3fb1": {"__data__": {"id_": "addff3b7-5011-43aa-a7b2-faa05f5b3fb1", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.12, para 6](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c05476b6-674d-41b2-84b7-5148b32ec4db", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.12, para 6](https://elifesciences.org/articles/95402)"}, "hash": "d3bbcbbc921a07ac5877a75ce8e3dcddc88c05b1161de3dfb9a50131f76a1831", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "While promoter-based transgenes for the vesicular transporter for GABA, unc-47/VGAT, had shown expression patterns that precisely match that of unc-25/GAD (Eastman et al., 1999), we had noted in our previous analysis of the GABA system that a fosmid-based reporter showed much broader expression in many additional neuron classes that showed no sign of GABA usage (Gendrel et al., 2016). In several of these neuron classes both the fosmid-based reporter and the CeNGEN scRNA data indicate very robust expression (e.g. AIN, SIA, SDQ), while in many others scRNA transcripts are only evident at looser thresholds and, correspondingly, fosmid-based reporter expression in these cells is often weak (Supplementary file 1; Gendrel et al., 2016). To investigate this matter further, we CRISPR/Cas9-engineered a gfp-based reporter allele for unc-47, syb7566, and first crossed it with an mCherry-based unc-47 fosmid-based reporter (otIs564) as a first-pass assessment for any obvious overlaps and mismatches of expression patterns between the two (Figure 5B, left side panels). The vast majority of neurons exhibited overlapping expression between syb7566 and otIs564. There were also many notable similarities in the robustness of expression of the fosmid-based reporter and the reporter allele (Supplementary file 1). In a few cases where the fosmid-based reporter expression was so dim that it is only detectable via antibody staining against its fluorophore (mCherry) (Gendrel et al., 2016; Serrano-Saiz et al., 2017b), the reporter allele expression was readily visible (Supplementary file 1). The very few mismatches of expression of the fosmid-based reporter and the reporter allele included the pharyngeal neuron M1, which expresses no visible unc-47(syb7566) reporter allele but weak fosmid-based reporter expression, and the pharyngeal neuron I1, which expresses dim syb7566 but no fosmid-based reporter (Figure 5B, right side panels). AVJ shows very dim and variable unc-47(syb7566) reporter allele expression but no fosmid-based reporter expression. Since AVJ stains with anti-GABA antibodies (Gendrel et al., 2016), this neuron likely engages in vesicular release of GABA, even though its source of GABA remains unclear since it neither expresses conventional GABA synthesis machinery (UNC-25/GAD) nor GABA uptake machinery (SNF-11). Other neurons previously shown to stain with anti-GABA antibodies and to express the unc-47 fosmid-based reporter (ALA and SMD) (Gendrel et al., 2016) still show expression of the unc-47 reporter allele.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2543, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "802735a7-a152-4757-aea0-ee07c36eb2cd": {"__data__": {"id_": "802735a7-a152-4757-aea0-ee07c36eb2cd", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.12, para 7](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "086ded94-8404-4027-983c-6db5963196a1", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.12, para 7](https://elifesciences.org/articles/95402)"}, "hash": "85a88e01105ec33b235ba7a5bcc0e3cb5fe0dad9eac6af57956d0dac7819751a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In addition, while the reporter allele of unc-47/VGAT, in conjunction with CeNGEN scRNA data, corroborates the notion that unc-47/VGAT is expressed in all GABA-synthesizing and most GABA uptake neurons, there is a substantial number of unc-47-positive neurons that do not show any evidence of GABA presence. This suggests that UNC-47/VGAT may transport another unidentified neurotransmitter (see Discussion) (Gendrel et al., 2016).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 431, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "35889d2b-a918-4183-96b0-4de1bc57d4e8": {"__data__": {"id_": "35889d2b-a918-4183-96b0-4de1bc57d4e8", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.12, para 8](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9757592a-14f8-40ca-b3f0-0f25ffdba56b", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.12, para 8](https://elifesciences.org/articles/95402)"}, "hash": "5407e9a459a563a84f1d3f1487a462d8f15e7d4d6b6f21f686abe16fba5131fd", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Expression of unc-46/LAMP", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 28, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c043b65b-c515-43ab-b4af-0b9b8a00fe7c": {"__data__": {"id_": "c043b65b-c515-43ab-b4af-0b9b8a00fe7c", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.12, para 9](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e2d6dc61-795d-4f86-a6a0-210d2bd9704c", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.12, para 9](https://elifesciences.org/articles/95402)"}, "hash": "44f2ae9af1f13227fec6bcaa426f8cc439751186b6597b06bd48ec164d9311ac", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In all GABA-synthesizing neurons, the UNC-47/VGAT protein requires the LAMP-like protein UNC-46 for proper localization (Schuske et al., 2007). A previously analyzed fosmid-based reporter confirmed unc-46/LAMP expression in all \u2018classic\u2019 GABAergic neurons (i.e. anti-GABA and unc-25/GAD-positive neurons), but also showed robust expression in GABA- and unc-47-negative neurons, such as RMD (Gendrel et al., 2016). This non-GABAergic neuron expression is confirmed by CeNGEN scRNA", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 479, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6e2c1bd9-91a7-40a7-8a6d-d55e26c8b655": {"__data__": {"id_": "6e2c1bd9-91a7-40a7-8a6d-d55e26c8b655", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.13, para 1](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e79c414b-ccd8-406e-aa21-f0a262ef0f24", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.13, para 1](https://elifesciences.org/articles/95402)"}, "hash": "18d2f51091a656ad9e69416a2924b79b9926e747000e6b43d88ead421e14523e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "data (Taylor et al., 2021; Supplementary file 1). We generated an unc-46/LAMP reporter allele, syb7278, and found its expression to be largely similar to that of the fosmid-based reporter and to the scRNA data (Figure 5C, Supplementary file 1), therefore corroborating the non-GABAergic neuron expression of unc-46/LAMP. We also detected previously unreported expression in the PVW and PVN neurons in both the reporter allele and fosmid-based reporter (Figure 5C), thereby further corroborating CeNGEN data. In addition, we also detected very dim expression in PDA (Figure 5C), which shows no scRNA transcript reads (Supplementary file 1). With one exception (pharyngeal M2 neuron class), the sites of non-GABAergic neuron expression of unc-46/LAMP expression do not show any overlap with the sites of unc-47/VGAT expression, indicating that these two proteins have functions independent of each other.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 902, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "804af55d-4047-42f7-aec6-b7056858d6b5": {"__data__": {"id_": "804af55d-4047-42f7-aec6-b7056858d6b5", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.13, para 2](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "097081ba-dfe9-410c-a67f-69b430a79420", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.13, para 2](https://elifesciences.org/articles/95402)"}, "hash": "ef1971841eb75aa2720214ac353422d15aa66d30fcbdc2a48b11ff78db418ac7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Expression of reporter alleles for serotonin biosynthetic enzymes, tph-1/TPH and bas-1/AAAD, in the hermaphrodite", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 116, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6efd8f22-c177-4aba-9b9d-460b9c1d7a2c": {"__data__": {"id_": "6efd8f22-c177-4aba-9b9d-460b9c1d7a2c", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.13, para 3](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "be5db728-8fba-4fd7-bd9c-2a349a59a603", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.13, para 3](https://elifesciences.org/articles/95402)"}, "hash": "27a8a047599c5de0cba79bbb380bbe73243535a1421774fdbbe30d97d600ba87", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "tph-1/TPH and bas-1/AAAD code for enzymes required for serotonin (5-HT = 5-hydroxytryptamine) synthesis (Figure 1A). scRNA transcripts for tph-1 and bas-1 are detected in previously defined serotonergic neurons at all four threshold levels (HSN, NSM, ADF) (Figure 1, Supplementary file 1). In addition to these well-characterized sites of expression, several of the individual genes show scRNA-based transcripts in a few additional cells: tph-1 at all four threshold levels in AFD and MI. Neither of these cells display scRNA transcripts for bas-1/AAAD, the enzyme that metabolizes the TPH-1 product 5-HTP (5-hydroxytryptophan) into serotonin (5-HT) (Figure 1A). To further investigate these observations, we generated reporter alleles for both tph-1 and bas-1 (Figure 2). Expression of the tph-1 reporter allele syb6451 confirmed expression in the previously well-described neurons that stained positive for serotonin, namely NSM, HSN, and ADF, matching CeNGEN data. While expression in AFD (seen at all four threshold levels in the CeNGEN scRNA atlas) could not be confirmed with the reporter allele, expression in the pharyngeal MI neurons could be confirmed (Figure 6A, Figure 6\u2014figure supplement 1, Supplementary file 2).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1226, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7aba30f0-b03e-4915-b550-d0e55e37fffe": {"__data__": {"id_": "7aba30f0-b03e-4915-b550-d0e55e37fffe", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.13, para 4](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1e2abb07-c0ad-4c5b-9648-39e76e91f1bf", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.13, para 4](https://elifesciences.org/articles/95402)"}, "hash": "17acb4257605e0659ac14c2a689aac4ac70dd10d8e837442d0222a7f6975fc0c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We detected co-expression of the bas-1 reporter allele, syb5923, with tph-1(syb6451) in NSM, HSN, and ADF, in accordance with the previous reporter and scRNA data (Figure 6B, Supplementary file 2). However, bas-1(syb5923) is not co-expressed with tph-1 in MI (Figure 6A and B), nor is there CeNGEN-transcript evidence for bas-1/AAAD in MI (Figure 1, Supplementary file 1). Hence, TPH-1-synthesized 5-HTP in MI is not metabolized into 5-HT (serotonin), consistent with the lack of serotonin-antibody staining in MI (Horvitz et al., 1982; Sze et al., 2000).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 555, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3596712b-d716-41c3-9f5b-3799c542cd17": {"__data__": {"id_": "3596712b-d716-41c3-9f5b-3799c542cd17", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.13, para 5](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "94ee5cc8-43ec-4c5d-ab58-8011bb32859e", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.13, para 5](https://elifesciences.org/articles/95402)"}, "hash": "0dc930d4e46877c5ec4185e84b29d6073e05c1e8acc55bef4a6c3442e2ee8872", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We also detected tph-1(syb6451) reporter allele expression in the serotonergic VC4 and VC5 neurons (Figure 6A, Supplementary file 2), consistent with scRNA data (Figure 1, Supplementary file 1) and previous reporter transgene data (Mondal et al., 2018). This suggests that these neurons are capable of producing 5-HTP. However, there is no bas-1(syb5923) expression in VC4 or VC5, consistent with previous data showing that serotonin is taken up, but not synthesized by them (Duerr et al., 2001) (more below on monoamine uptake; Tables 1 and 2).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 545, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0bbea4d4-f225-4942-bd92-6e7038d1f084": {"__data__": {"id_": "0bbea4d4-f225-4942-bd92-6e7038d1f084", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.13, para 6](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6e81a788-c30d-4c7a-ab29-769be8163f60", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.13, para 6](https://elifesciences.org/articles/95402)"}, "hash": "c577279c9bf790f37f5d864bdcd5533c57485a72814188fede082ac26f000744", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "As expected from the role of bas-1/AAAD in dopamine synthesis (Hare and Loer, 2004), bas-1(syb5923) is also expressed in dopaminergic neurons PDE, CEP, and ADE. In addition, it is also expressed weakly in URB, consistent with scRNA data. We did not detect visible expression in PVW or PVT, both of which showed very low levels of scRNA transcripts (Figure 1, Supplementary file 1). Expression of bas-1/AAAD in URB may suggest that URB generates a non-canonical monoamine (e.g. tryptamine, phenylethylamine \\[PEA], or histamine), but since URB expresses no vesicular transporter (cat-1/VMAT, see below), we consider it unlikely that any such monoamine would be secreted via canonical vesicular synaptic release mechanisms.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 721, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "35253c5a-ecff-4063-80ba-8bee661572b7": {"__data__": {"id_": "35253c5a-ecff-4063-80ba-8bee661572b7", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.13, para 7](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "38395299-e525-4abd-9156-d17876ce808f", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.13, para 7](https://elifesciences.org/articles/95402)"}, "hash": "ad96f239ad37a245a2a42c7b4b8886cec7248988fb079bd3c38955b0f5c3af3f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Expression of a reporter allele of cat-2/TH, a dopaminergic marker, in the hermaphrodite", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 91, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4517dc31-f2c3-44d5-a06d-bd54d2807141": {"__data__": {"id_": "4517dc31-f2c3-44d5-a06d-bd54d2807141", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.13, para 8](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2dfe197c-e4a5-430d-bf05-a714614ee6e1", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.13, para 8](https://elifesciences.org/articles/95402)"}, "hash": "98b57bf261aa3f2002831530f74d22d9269a3175cef906605810e9e6ee3ba5f0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The CeNGEN scRNA atlas shows transcripts for the rate-limiting enzyme of dopamine synthesis encoded by cat-2/TH (Figure 1B, Supplementary file 1) at all four threshold levels in all three previously described dopaminergic neuron classes in the hermaphrodite, ADE, PDE, and CEP (Sulston et al., 1975; Sulston et al., 1980; Lints and Emmons, 1999). At lower threshold levels, transcripts can also be detected in the OLL neurons. A CRISPR/Cas9-engineered reporter allele for cat-2/TH, syb8255, confirmed expression in ADE, PDE, and CEP in adult hermaphrodites (Figure 7A, Supplementary file", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 587, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3c332fde-b907-4081-9241-0d9c1466a236": {"__data__": {"id_": "3c332fde-b907-4081-9241-0d9c1466a236", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.14, para 0](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1a226951-11b6-4453-80f1-36c44c836966", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.14, para 0](https://elifesciences.org/articles/95402)"}, "hash": "dfb626e366d632091f0444bc0b15af10922efd7fce1b3f51bea7f86a96adf796", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Figure 6. Expression of tph-1/TPH, bas-1/AAAD, and cat-1/VMAT reporter alleles in the adult hermaphrodite.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 108, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "30323e63-7cef-4a71-911f-bd519073329a": {"__data__": {"id_": "30323e63-7cef-4a71-911f-bd519073329a", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.14, para 1](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8843e6fe-b1ea-4548-8aee-a4649016bc6f", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.14, para 1](https://elifesciences.org/articles/95402)"}, "hash": "9368d5cb20a0212ee95d60ccd64b07b0bf3be447cc9da3952c78f4d0dd7e4a13", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "(A) Dorsoventral view of a hermaphrodite head and midbody expressing tph-1(syb6451). tph-1 expression is detected robustly in the MI neuron and dimly and variably in VC4 and VC5. Neuron identities for MI and VC4 and VC5 were validated using otIs518\\[eat-4(fosmid)::sl2::mCherry::h2b] and vsls269\\[ida-1::mCherry], respectively, as", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 330, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b3ba8bdf-31a6-4e30-976b-df4d85649d19": {"__data__": {"id_": "b3ba8bdf-31a6-4e30-976b-df4d85649d19", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.14, para 2](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4d9c329d-7725-4a7c-9635-88a6b0c38c1a", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.14, para 2](https://elifesciences.org/articles/95402)"}, "hash": "68bf41f4922d0728637a5cdf5a7ac86ef8c34725319733925ed5bff866eb5515", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|tph-1CRISPR::gfp|marker|MERGE|\n|-|-|-|\n|D/V view|eat-4fosmid::sl2::mCherry::h2b||\n|NSM||NSM|\n|ADF||ADF|\n|MI||MI|\n|MI||MI|\n\n|vulval region ventral view|ida-1p::mCherry||\n|-|-|-|\n|HSN||HSN|\n|VC4||VC4|\n|VC5||VC5|\n|HSN||HSN|\n|HSN||HSN|\n\n|HERM HEAD|HERM MIDBODY||\n|-|-|-|\n|D/V view|PDE||\n|NSM||HSN|\n|URB||HSN|\n|CEPD||HSN|\n|ADF||HSN|\n|ADE||HSN|\n|CEPV||HSN|\n|NSM||HSN|\n|URB||HSN|\n|CEPD||HSN|\n|ADE||HSN|\n|CEPV||HSN|\n|NSM||HSN|\n|URB||HSN|\n|CEPD||HSN|\n|ADE||HSN|\n|CEPV||HSN|\n|NSM||HSN|\n|URB||HSN|\n|CEPD||HSN|\n|ADE||HSN|\n|CEPV||HSN|\n\n|HERM HEAD|HERM MIDBODY||\n|-|-|-|\n|lateral view|lateral view||\n|CEPD||CAN|\n|ASI||CAN|\n|ADF||VC4|\n|RIM||HSN|\n|RIC||VC5|\n|CEPV||PDE|\n|RIH||PDE|\n|RIR||PDE|\n|AVL(+/-)||PDE|\n|NSML/R||VC4|\n|||HSN|\n|||VC5|\n\n|HERM HEAD|HERM MIDBODY||\n|-|-|-|\n|lateral view|lateral view||\n|CEPD||CAN|\n|ASI||CAN|\n|ADF||VC4|\n|RIM||HSN|\n|RIC||VC5|\n|CEPV||PDE|\n|RIH||PDE|\n|RIR||PDE|\n|AVL||PDE|\n|NSML/R||VC4|\n|||HSN|\n|||VC5|\n\n|HERM HEAD|HERM MIDBODY||\n|-|-|-|\n|lateral view|lateral view||\n|CEPD||CAN|\n|ASI||CAN|\n|ADF||VC4|\n|RIM||HSN|\n|RIC||VC5|\n|CEPV||PDE|\n|RIH||PDE|\n|RIR||PDE|\n|AVL||PDE|\n|NSML/R||VC4|\n|||HSN|\n|||VC5|", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1112, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9ce02ec9-fac3-407a-bfbd-8646732cd1ea": {"__data__": {"id_": "9ce02ec9-fac3-407a-bfbd-8646732cd1ea", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.15, para 1](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "eafaba1c-0a51-4e39-b5bb-fb97fb744bce", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.15, para 1](https://elifesciences.org/articles/95402)"}, "hash": "bd465cacdb0e05935e82442ff98d3d59bfdc6e5ae23907b7647f07770ebd5ab2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Figure 6 continued\nlandmarks. Inset, grayscale image highlighting dim expression in VC4. Larval expression of this reporter allele is shown in Figure 6\u2014figure supplement 1. (B) Neuronal expression of bas-1(syb5923) characterized with the landmark NeuroPAL (otIs669) strain in the head and midbody regions of young adult hermaphrodites. Dorsoventral view of the adult head shows bas-1/AAAD expression in left-right neuron pairs, including previously reported expression in NSM, CEP, ADF, and ADE (Hare and Loer, 2004). Additionally, we observed previously unreported expression in the URB neurons. Non-neuronal bas-1/AAAD expression is detected in other non-neuronal cell types as reported previously (Yu et al., 2023; also see Figure 14\u2014figure supplement 1, Figure 14). (C) Lateral views of young adult hermaphrodite head and midbody expressing cat-1/VMAT (syb6486). Previously unreported cat-1/VMAT expression is seen in RIR, CAN, AUA, ASI (also in inset), and variably, AVL. Non-neuronal expression of cat-1/VMAT is detected in a single midbody cell in the gonad (also see Figure 14\u2014figure supplement 1), marked with an asterisk. Scale bars, 10 \u00b5m for all color images; 5 \u00b5m for the inset in grayscale.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1204, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9c9b54e1-5abd-4713-8719-ed05e38428c4": {"__data__": {"id_": "9c9b54e1-5abd-4713-8719-ed05e38428c4", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.15, para 2](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "edb110a5-5ed5-429e-a4af-6e04eb7493c2", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.15, para 2](https://elifesciences.org/articles/95402)"}, "hash": "076abf132f79ea51b4584b3632edff3303933166b499de2ad9aebd95c9604e64", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The online version of this article includes the following figure supplement(s) for figure 6:\nFigure supplement 1. tph-1/TPH reporter allele expression in the hermaphrodite larvae.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 179, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "143d2874-53a2-4e63-b57f-e75446b1e06e": {"__data__": {"id_": "143d2874-53a2-4e63-b57f-e75446b1e06e", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.15, para 3](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d0670cc6-b4e4-45da-92c1-fa742e8bab77", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.15, para 3](https://elifesciences.org/articles/95402)"}, "hash": "91d69b80fb059d8491e835d454c0b9b00d0726f97a896b1dfd68ff4397d14fc4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "2\\). As expected and described above, all three neuron classes also expressed bas-1/AAAD (Figure 6B) and cat-1/VMAT (Figure 6C, see below) (Supplementary file 2). We did not detect visible expression of cat-2(syb8255) in OLL. The OLL neurons also display no scRNA transcripts or reporter allele expression of bas-1/AAAD or cat-1/VMAT. No additional sites of expression of cat-2(syb8255) were detected in the adult hermaphrodite.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 428, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c35cd1be-266c-4e90-ac69-fc5c55859d32": {"__data__": {"id_": "c35cd1be-266c-4e90-ac69-fc5c55859d32", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.15, para 4](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e6ca1fd6-bb90-41a0-8ec8-d4538c48f1f6", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.15, para 4](https://elifesciences.org/articles/95402)"}, "hash": "6594402f585b87e29e4ac6e5833e85e41c0397114746941817a2023e5847144b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Expression of reporter alleles of tdc-1/TDC and tbh-1/TBH, markers for tyraminergic and octopaminergic neurons, in the hermaphrodite", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 135, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3c6b05d8-3fd2-4a8d-ab4e-998f39c7978f": {"__data__": {"id_": "3c6b05d8-3fd2-4a8d-ab4e-998f39c7978f", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.15, para 5](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9e8e2980-ef21-49c1-b8eb-5c8e57a5535e", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.15, para 5](https://elifesciences.org/articles/95402)"}, "hash": "60c75301998a39e51c2e1becdbf5ab10090ee1d4a2c7c335011ec48b40a90b35", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The invertebrate analogs of adrenaline and noradrenaline, tyramine and octopamine, are generated by tdc-1 and tbh-1 (Figure 1A; Alkema et al., 2005). Previous work had identified expression of tdc-1 in the hermaphrodite RIM and RIC neurons and tbh-1 in the RIC neurons (Alkema et al., 2005). Transcripts in the CeNGEN atlas match those sites of expression for both tdc-1 (scRNA at four threshold levels in RIM and RIC neurons) and tbh-1 (scRNA at four threshold levels in RIC neurons) (Figure 1B, Supplementary file 1). Much lower transcript levels are present in a few additional, non-overlapping neurons (Figure 1B). CRISPR/Cas9-engineered reporter alleles confirmed tdc-1 expression in RIM and RIC and tbh-1 expression in RIC (Figure 7B and C, Supplementary file 2). In addition, we also detected dim expression of tbh-1(syb7786) in all six IL2 neurons, corroborating scRNA transcript data (Figure 7C, Supplementary files 1 and 2). However, IL2 neurons do not exhibit expression of the reporter allele of tdc-1, which acts upstream of tbh-1 in the octopamine synthesis pathway, or of cat-1/VMAT, the vesicular transporter for octopamine (Figure 6C, see below). Hence, the IL2 neurons are unlikely to produce or synaptically release octopamine, but they may produce another monoaminergic signal (Table 2).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1307, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "28711aa5-c2f7-468c-8a73-61fd3254e5c6": {"__data__": {"id_": "28711aa5-c2f7-468c-8a73-61fd3254e5c6", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.15, para 6](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a978f76f-e654-4d78-9862-2f2e7436c2eb", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.15, para 6](https://elifesciences.org/articles/95402)"}, "hash": "f9f6600e79cc0307c978d666e81d6b9c7a712e5fed50eeefa9c10a48dfd41894", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Expression of a reporter allele of cat-1/VMAT, a marker for monoaminergic identity, in the hermaphrodite", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 107, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0b6bf94b-1173-4ce5-b8d1-b7e0100c2916": {"__data__": {"id_": "0b6bf94b-1173-4ce5-b8d1-b7e0100c2916", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.15, para 7](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e50e94f8-4ad5-4c25-a6d2-ec37c6262f56", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.15, para 7](https://elifesciences.org/articles/95402)"}, "hash": "9b38edd66fd571fd693d0a62088063fa9713b3b8fb0033b322584ffe5709186f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "As the vesicular monoamine transporter, cat-1/VMAT is expected to be expressed in all neurons that synthesize serotonin, dopamine, tyramine, and octopamine (Figure 1A). Both scRNA data and a CRISPR/Cas9-engineered reporter allele, syb6486, confirm expression in all these cells (Figure 6C, Supplementary file 2). In addition, based on antibody staining and previous fosmid-based reporters, cat-1/VMAT is known to be expressed in neurons that do not synthesize serotonin but are nevertheless positive for serotonin antibody staining (VC4, VC5, and RIH) (Duerr et al., 1999; Duerr et al., 2001; Serrano-Saiz et al., 2017b). Again, both scRNA data and a CRISPR/Cas9-engineered reporter allele, syb6486, confirm expression in these cells (Figure 6C, Supplementary file 2).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 768, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b7d0e6ec-c391-4ab3-a364-c5b1b24d1c11": {"__data__": {"id_": "b7d0e6ec-c391-4ab3-a364-c5b1b24d1c11", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.15, para 8](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0016c585-858f-4509-9526-84df21253cbd", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.15, para 8](https://elifesciences.org/articles/95402)"}, "hash": "c4a448c63c7e299c027551c0a2eaedf19cfa93e5fa5460b49242c35a346cdbb9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In addition to these canonical monoaminergic neurons, the CeNGEN scRNA data shows cat-1/VMAT expression at all four threshold levels in RIR, CAN, AVM and, at a much lower threshold, eight additional neuron classes (Figure 1B, Supplementary file 1). Our cat-1/VMAT reporter allele, syb6486, corroborates expression in RIR and CAN, but not in AVM (Figure 6C, Supplementary file 2). We also observed expression of the cat-1 reporter allele in two of the neuron classes with scRNA transcripts at the lowest threshold level, ASI and variably, AVL (Figure 6C, Supplementary file 1). Interestingly, AVL does not express any other monoaminergic pathway genes (Supplementary file 2), therefore it", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 687, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3787d972-0760-49cc-9fba-61c019f5807d": {"__data__": {"id_": "3787d972-0760-49cc-9fba-61c019f5807d", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.16, para 1](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ac3ff9d0-93cf-484c-b453-64d9e6e3836a", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.16, para 1](https://elifesciences.org/articles/95402)"}, "hash": "915628ff657e2fb17a115c4c77a439333afb0a1084243d94a58ad4f5d0a0fea3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Table 1. Neurons that uptake monoaminergic neurotransmitters.\n+: presence of reporter allele expression; -: lack of visible reporter allele expression; +/-: dim and variable expression (variability is only detected when reporter fluorescent intensity is low); m: anti-serotonin staining observed in males; \\*: sex-specific neurons; \\*\\*: variable/very dim antibody staining reported in previous publications. \\*\\*\\*N/A=not presently applicable because betaine is provided by diet, in addition to possible endogenous synthesis. See text for citations.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 550, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6d233c1c-83a8-4d73-b5a9-d44c71640b1b": {"__data__": {"id_": "6d233c1c-83a8-4d73-b5a9-d44c71640b1b", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.16, para 2](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5129224a-f50d-43af-8c54-3e76929ea162", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.16, para 2](https://elifesciences.org/articles/95402)"}, "hash": "594336f82f07f7a0d21ce5a8c7a66512b09056ca4d843abc1288265c81e1720c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|||Uptake|Synthesis|Release|\n|-|-|-|-|-|\n||Neuron|mod-5|tph-1|cat-1|\n||ADF|+|+|+|\n||AIM|+|-|-|\n||I5\\*\\*|-|-|+/-|\n||NSM|+|+|+|\n||PVW(m)\\*\\*|-|-|-|\n||RIH|+|-|+|\n||URX\\*\\*|+/-|-|-|\n||\\*HSN|-|+|+|\n||\\*VC4-5\\*\\*|-|+/-|+|\n||\\*CEM\\*\\*|+|+|-|\n||\\*CP1-6|+|+|+|\n||\\*PGA|+|-|+|\n||\\*R1B|-|+|+|\n||\\*R3B|+|+|+|\n|Serotonin|\\*R9B|+|+|+|\n||Neuron|oct-1|tdc-1|cat-1|\n|Tyramine|RIM|+|+|+|\nTable 1 continued on next page", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 400, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0ccdb9f2-92aa-4613-ba98-d53b74f8dd04": {"__data__": {"id_": "0ccdb9f2-92aa-4613-ba98-d53b74f8dd04", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.17, para 2](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8d466e09-94c5-4089-9ae7-4a129e917458", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.17, para 2](https://elifesciences.org/articles/95402)"}, "hash": "b8be72de78cdfd2f694f0ef24cea442bd4a26959dc20522887a6e599d1633814", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Neuron|Uptake|Synthesis|Release|\n|-|-|-|-|\n||\\*snf-3\\*|N/A\\*\\*\\*|\\*cat-1\\*|\n|AUA|+||+|\n|CAN|+||+|\n|NSM|+/-||+|\n|RIM|+||+|\n|RIR|+/-||+|\n|ASI|+/-||+|\n|M3|+/-||-|\n|AIB|+||-|\n|DVB|+/-||-|\n|SMD|+/-||-|\n|RIS|+||-|\n|URX|+/-||-|\n|PDA|+/-||-|\n|ASG|+/-||-|\n|DA9|+/-||-|\n|VB1-11|+/-||-|\n|PHC|+||-|\n|PVN|+||-|\n|VA12|+/-||-|\n|RMH|+/-||-|\n|\\*PDC|+||+|\n|\\*PHD|+||-|\n|Betaine|\\*PVV|+/-|-|\nmay be transporting a new amine yet to be discovered. This scenario also applies for two male-specific neurons (more below). As previously mentioned, we detected no *cat-1/VMAT* expression in the *tph-1/TPH*-positive MI or the *cat-2/TH*-positive OLL neurons.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 633, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8ecbd7ee-1190-4d2e-acf5-0af5e7ebb3e0": {"__data__": {"id_": "8ecbd7ee-1190-4d2e-acf5-0af5e7ebb3e0", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.17, para 3](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d900950f-2b81-49da-a9af-672bcdf259b2", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.17, para 3](https://elifesciences.org/articles/95402)"}, "hash": "59c3708e45f48f6dd9f9b6a30f443548b875240cb346f2004da50943862b91ef", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The *cat-1/VMAT* reporter allele revealed expression in an additional neuron class, the AUA neuron pair (Figure 6C, Supplementary file 2). Expression in this neuron is not detected in scRNA data; however, such expression may be consistent with previous CAT-1/VMAT antibody staining data (Duerr *et al.*, 1999). These authors found the same expression pattern as we detected with *cat-1/VMAT* reporter allele, except for the AIM neuron, which Duerr *et al.* identified as CAT-1/VMAT antibody-staining positive. However, neither our reporter allele, nor a fosmid-based *cat-1/VMAT* reporter, nor scRNA data showed expression in AIM, and we therefore think that the neurons identified by Duerr *et al.* as AIM may have been the AUA neurons instead (see also Serrano-Saiz *et al.*, 2017b). Additionally, a *cat-1*-positive neuron pair in the ventral ganglion, unidentified but mentioned by Duerr *et al.*, 1999, is likely the tyraminergic RIM neuron pair, based on our reporter allele and CeNGEN scRNA data.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1003, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c2e88c70-9bd9-4015-a83b-5377b5665397": {"__data__": {"id_": "c2e88c70-9bd9-4015-a83b-5377b5665397", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.17, para 4](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5fa24cb2-a83a-4d1c-87b9-2e60262baa30", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.17, para 4](https://elifesciences.org/articles/95402)"}, "hash": "58146dd95a8018ec10d88cfaedf9063c38838f51ef9cffcb443ad56dba35d6ba", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Expression of reporter alleles of monoamine uptake transporters in the hermaphrodite", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 87, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "070c7ec9-0b25-4967-98c3-f50faa819b7a": {"__data__": {"id_": "070c7ec9-0b25-4967-98c3-f50faa819b7a", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.17, para 5](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bda4faad-f0d6-4a54-9db1-fa71d7cd5c16", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.17, para 5](https://elifesciences.org/articles/95402)"}, "hash": "e82a7596f9ce11d249b902c73f2a793701138edb5145752498f482dcebfc2f91", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In addition to or in lieu of synthesizing monoamines, neurons can uptake them from their surroundings. To investigate the cellular sites of monoamine uptake in more detail, we analyzed fluorescent protein expression from engineered reporter alleles for the uptake transporter of serotonin (*mod-5*/", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 298, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b7c15b45-4048-4f60-b510-203d011251a7": {"__data__": {"id_": "b7c15b45-4048-4f60-b510-203d011251a7", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.18, para 0](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ea60b957-0959-4933-a285-865fc1952884", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.18, para 0](https://elifesciences.org/articles/95402)"}, "hash": "46c184f7474eae55f9e12987392dfe2be5015d08567a4d733d3820baa34b7187", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# eLife Tools and resources", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 27, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "02b5bc88-ff33-41c5-ad9c-cf1cb32790ce": {"__data__": {"id_": "02b5bc88-ff33-41c5-ad9c-cf1cb32790ce", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.18, para 2](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "74529878-9973-489f-8889-08aa087ad983", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.18, para 2](https://elifesciences.org/articles/95402)"}, "hash": "51c413df153d9ce51ffdd365e01f70d22cc3db5bf70dc55c280df75320748117", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Table 2. Categories of neuronal expression patterns for monoaminergic neurotransmitter pathway genes.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 101, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ef2623f8-0b0e-4002-996c-f2b1f0e9d3e2": {"__data__": {"id_": "ef2623f8-0b0e-4002-996c-f2b1f0e9d3e2", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.18, para 3](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "45d8c5e9-0d1b-4810-a542-3fd6eafc67c5", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.18, para 3](https://elifesciences.org/articles/95402)"}, "hash": "5445e82ba606e8903b462cf27a2fbdfde5f40dcf163fe0463b21338226a487b6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Criteria for monoaminergic neurotransmitter assignment and a summary for neurons with updated identities are presented here. The categories represent our best assessments based on available data; in every category there is a possibility for the existence of non-canonical synthesis and/or uptake mechanisms that are yet to be discovered. +: presence of reporter allele expression (incl. dim); -: lack of visible reporter allele expression; bas-1-dependent unknown monoamine?=bas-1-dependent unknown monoamine (histamine, tryptamine, PEA; see Figure 1\u2014figure supplement 1A and Discussion); unknown monoamine?=potentially non-canonical monoamines; see Discussion and Results sections on specific gene expression patterns; 5-HT=5-hydroxytryptamine, or serotonin; 5-HTP=5-hydroxytryptophan; PEOH = \u03b2-hydroxyphenethylamine, or phenylethanolamine; \\*: The expression of tph-1 in VC4-5, bas-1 in R4B and R6B, cat-1 in AVL, and snf-3 in NSM, RIR, ASI, URX, M3, DVB, SMD, PDA, ASG, DA9, VA12, VB1-11, RMH, and PVV is dim and variable (this study; variability is only detected when reporter fluorescent intensity is low); anti-5-HT staining in VC4, VC5, CEM, I5, URX, and PVW (male) is variable in previous reports (see text for citations). \\*\\* indicates that R4B and R7B express 5-HT synthesis machinery (tph-1 and bas-1), but do not stain with 5-HT antibodies.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1353, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "63a40d45-f3cd-4e57-b8e5-1b7d88f6c4ab": {"__data__": {"id_": "63a40d45-f3cd-4e57-b8e5-1b7d88f6c4ab", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.18, para 4](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a1b0753a-0ced-4c9a-9b0b-c619c426a6da", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.18, para 4](https://elifesciences.org/articles/95402)"}, "hash": "a122920dd1f6da655d747eeee0e718d0d1e5d9069c378e0cd9ebedcf6251bd69", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Synthesis (and/or uptake)|cat-1|tph-1|cat-2|bas-1|tdc-1|tbh-1|mod-5|snf-3|oct-1|Direct staining|Sex-specific neurons|Sex-shared neurons|\n|-|-|-|-|-|-|-|-|-|-|-|-|-|\n|Tyramine+bas-1-dependent unknown monoamine?|+|-|-|+|+|-|-|-|-||HOA||\n|Tyramine+bas-1-dependent unknown monoamine?|-|-|-|+|+|-|-|-|-||R8A||\n|Tyramine+dopamine|+|-|+|+|+|-|-|-|-|Dopamine|R7A||\n|Tyramine (+uptake)+betaine (uptake)|+|-|-|-|+|-|-|+|+|||RIM|\n|bas-1-dependent unknown monoamine?|+|-|-|+|-|-|-|-|-||R2A||\n|bas-1-dependent unknown monoamine?|-|-|-|+|-|-|-|-|-||R3A, R6A, R6B\\*, PCB, SPC, DVE, DVF|URB|\n|Octopamine|+|-|-|-|+|+|-|-|-|||RIC|\n|Octopamine|-|-|-|-|+|+|-|-|-||R8B||\n|Dopamine|+|-|+|+|-|-|-|-|-|Dopamine|R5A, R9A|ADE, CEP, PDE|\n|5-HTP (synthesis)+5-HT (alternative synthesis/uptake mechanism?)+unknown monoamine?|-|+|-|-|-|+|-|-|-|5-HT||CEM\\*|\n|5-HTP|-|+|-|-|-|-|-|-|-|||MI|\n|PEOH?|-|-|-|+|-|+|-|-|-||R2B||\n|5-HT+PEOH?|-|+|-|+|-|+|-|-|-||R7B\\*\\*||\n|5-HT+PEOH?|+|+|-|+|-|+|-|-|-|5-HT||R1B|\n|5-HT+PEOH?|+|+|-|+|-|+|+|-|-|5-HT||R3B|\n|5-HT+PEOH?|+|+|-|+|-|+|-|-|-||R4B\\*\\*||\n|5-HT (uptake)|+|-|-|-|-|-|+|-|-|5-HT|PGA|RIH|\n|5-HT (uptake)|-|-|-|-|-|-|+|-|-|5-HT||AIM|\n|5-HT (uptake)+betaine (uptake)|-|-|-|-|-|-|+|+|-|5-HT||URX\\*|\n|5-HT (& uptake)|+|+|-|+|-|-|+|-|-|5-HT|CP1-6|ADF|\n|5-HT (alternative synthesis/uptake mechanism?)|-|-|-|-|-|-|-|-|-|5-HT||I5\\*, PVW (male only)|\n|5-HT|+|+|-|+|-|-|-|-|-|5-HT|HSN||\n|5-HTP (synthesis) and 5-HT (uptake)|+|+|-|-|-|+|+|-|-|5-HT|R9B||\n|5-HTP (synthesis) and 5-HT (alternative synthesis/uptake mechanism?)|+|+|-|-|-|-|-|-|-|5-HT||VC4-5\\*|\nTable 2 continued on next page", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1589, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3e121fe6-0796-4237-9416-2d991e4f8d19": {"__data__": {"id_": "3e121fe6-0796-4237-9416-2d991e4f8d19", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.19, para 0](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b7c1109e-73e0-442b-90d1-0b036f227c08", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.19, para 0](https://elifesciences.org/articles/95402)"}, "hash": "51d73d80a68f3001ba2cbc93f74e11bad36102f6e303d8b03ad8a2709c65268c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# eLife Tools and resources", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 27, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2389026f-3b17-4d97-ba3b-92d752e6a191": {"__data__": {"id_": "2389026f-3b17-4d97-ba3b-92d752e6a191", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.19, para 3](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8aca9a9c-4eba-4cc4-847f-60c8d8f94fca", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.19, para 3](https://elifesciences.org/articles/95402)"}, "hash": "60d1d4cb2b842c7389321ea9b4e270176edb00834afda787038e98fa8bd47c4d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Synthesis (and/or uptake)|cat-1|tph-1|cat-2|bas-1|tdc-1|tbh-1|mod-5|snf-3|oct-1|Direct staining|Sex-specific neurons|Sex-shared neurons|\n|-|-|-|-|-|-|-|-|-|-|-|-|-|\n|Unknown monoamine?|+|-|-|-|-|-|-|-|-||PVX, PVY|AVL\\*|\n|Unknown monoamine?|-|-|-|-|-|+|-|-|-||HOB, R5B|IL2|\n|5-HT+betaine (uptake)|+|+|-|+|-|-|-|+|-|5-HT||NSM\\*|\n|Betaine (uptake)|+|-|-|-|-|-|-|+|-||PDC|AUA, CAN, RIR\\*, ASI\\*|\n|Betaine (uptake)|-|-|-|-|-|-|-|+|-||PHD, PVV\\*|M3\\*, AIB, DVB\\*, SMD\\*, RIS, PDA\\*, ASG\\*, DA9\\*, PHC, PVN, VA12\\*, VB1-11\\*, RMH\\*|\nSERT(vlc47)), the predicted uptake transporter for tyramine (oct-1/OCT(syb8870)), and that for betaine (snf-3/BGT1(syb7290)).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 652, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3166aa57-5090-4b75-99ab-8b61c431cb01": {"__data__": {"id_": "3166aa57-5090-4b75-99ab-8b61c431cb01", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.19, para 4](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "af3691d4-f79b-452b-aa23-3be577226ab6", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.19, para 4](https://elifesciences.org/articles/95402)"}, "hash": "17d10a950d2f5209390b54082d4c7309a8862d92db5956c76b55b2664233954f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Serotonin/5-HT uptake", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 24, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "051134fd-7fb4-49a7-a3c8-1a2c7fc77fd2": {"__data__": {"id_": "051134fd-7fb4-49a7-a3c8-1a2c7fc77fd2", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.19, para 5](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3e841d7b-d45a-4a88-88c5-c46508980a53", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.19, para 5](https://elifesciences.org/articles/95402)"}, "hash": "4903efb182fd18f0fea0d7348ba9f7189955d5ca115204668262741a46113cd8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Using a promoter-based transgene and antibody staining, previous work had shown expression of the serotonin uptake transporter mod-5/SERT in NSM, ADF, RIH, and AIM (Jafari et al., 2011; Maicas et al., 2021). This matched the observations that RIH and AIM do not synthesize serotonin (i.e. do not express tph-1), but stain positive with a serotonin antibody (Jafari et al., 2011). In mod-5 mutants or wild type worms treated with serotonin reuptake inhibitors (such as the SSRI fluoxetine), RIH and AIM lose serotonin immunoreactivity (Jafari et al., 2011). We analyzed a CRISPR-based reporter allele, mod-5(vlc47) (Maicas et al., 2021), and confirmed expression in the four neuron classes NSM, ADF, RIH, and AIM (Figure 8). Because only NSM, ADF, and RIH, but not AIM, express the reporter allele of the monoamine transporter CAT-1/VMAT (Figure 6), AIM likely functions as a serotonin uptake/clearance neuron (Tables 1 and 2; see also Discussion). In addition, we also detected dim mod-5/SERT expression in the phasmid neuron class PHA and very dim, variable signals in URX (Figure 8A, B, E) consistent with scRNA data (Supplementary file 1). The results for anti-serotonin-staining from previous reports are variable in a few neurons, possibly due to differences in staining methods (including URX, I5, VC4, VC5, and PVW Loer and Kenyon, 1993; Rand and Nonet, 1997; Duerr et al., 1999; Serrano-Saiz et al., 2017b). In light of its mod-5/SERT reporter expression, URX may acquire serotonin via mod-5, akin to AIM (Tables 1 and 2).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1530, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d48f585f-fe3e-44ab-b47d-c480ff601889": {"__data__": {"id_": "d48f585f-fe3e-44ab-b47d-c480ff601889", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.19, para 6](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f963ab20-5e39-46dd-ac69-b3e609230f01", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.19, para 6](https://elifesciences.org/articles/95402)"}, "hash": "f57f2ab76e996c61fbfbe35a440f655dfd02cb6d15e4a769c24045d903e7a921", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In the hermaphrodite-specific neurons HSN, VC4, and VC5, we did not observe expression of the mod-5/SERT reporter allele (Tables 1 and 2). Since VC4 and VC5 do not express the complete synthesis pathway for serotonin, we infer that the anti-serotonin staining in these neurons is a result of alternative serotonin uptake or synthesis mechanisms. A similar scenario holds for the pharyngeal neuron I5, which was previously reported to stain weakly for serotonin (Serrano-Saiz et al., 2017b).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 490, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3cf1d956-6a65-44c8-9b00-499611d826f6": {"__data__": {"id_": "3cf1d956-6a65-44c8-9b00-499611d826f6", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.19, para 7](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0a4729a2-217a-4b46-bdae-55ed7ff36182", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.19, para 7](https://elifesciences.org/articles/95402)"}, "hash": "08f55b68e38831200b507e0e9cb7ff9e86770a29370d3343936b16a46332da1d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Tyramine uptake", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 18, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "515cf73e-a887-4617-bd68-e536c41be9d7": {"__data__": {"id_": "515cf73e-a887-4617-bd68-e536c41be9d7", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.19, para 8](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ebecd8d2-89ee-4706-8a71-22436a1a02af", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.19, para 8](https://elifesciences.org/articles/95402)"}, "hash": "bf42d690bf8b4eb63d7d8a74706a43dcec015a0b6a78aed021d960e1c934f070", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Biochemical studies in vertebrates have shown that the SLC22A1/2/3 (aka OCT-1/2/3) organic cation transporters can uptake monoaminergic neurotransmitters (Nigam, 2018), with SLC22A2 being apparently selective for tyramine (Berry et al., 2016). oct-1 is the ortholog of the OCT subclass of SLC22 family members (Zhu et al., 2015), but neither its expression nor function in the nervous system had been previously reported. We tagged the endogenous oct-1 locus with an sl2::gfp::h2b cassette (syb8870) and, within the nervous system, observed exclusive expression in the RIM neuron (Figure 8H and I), indicating that RIM is likely capable of uptaking tyramine in addition to synthesizing it via tdc-1/TDC. This is consistent with RIM being the only neuron showing oct-1 scRNA transcripts at all four threshold levels in the CeNGEN atlas (Supplementary file 1).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 858, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4eb3ad86-5fba-4076-86eb-026ee25ab526": {"__data__": {"id_": "4eb3ad86-5fba-4076-86eb-026ee25ab526", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.20, para 0](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d1b82d30-0e17-4769-a0ff-60cb1a823b35", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.20, para 0](https://elifesciences.org/articles/95402)"}, "hash": "08f5fc3cae94e189cb80a99a8c4b11e1c7b088d62b0b65ef09c2b0da8b195de7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Figure 7. Expression of cat-2/TH, tdc-1/TDC, and tbh-1/TBH reporter alleles in the adult hermaphrodite. Neuronal expression was characterized with landmark strain NeuroPAL (otIs669). Lateral views of young adult hermaphrodites expressing reporter alleles for (A) cat-2(syb8255), (B) tbh-1(syb7786), and (C) tdc-1(syb7768). (A) cat-2/TH expression in CEP, ADE, and PDE match previously reported dopamine straining expression (Sulston et al., 1975). (B) and (C) Head areas are shown; no neuronal expression was detected in other areas. tdc-1 expression matches previous analysis (Alkema et al., 2005). We detected previously unreported expression of tbh-1 in all six IL2 neurons at low levels. Scale bars, 10 \u03bcm.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 712, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2601669e-13f4-43f7-b72d-08ec79bb3a5a": {"__data__": {"id_": "2601669e-13f4-43f7-b72d-08ec79bb3a5a", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.20, para 1](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "43670108-6d58-4eb7-a83d-45ce7b071d09", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.20, para 1](https://elifesciences.org/articles/95402)"}, "hash": "d5f97f0556a61fe6d70b7969a49d5239f96e95fade276dca5fa093401ab21abf", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## A", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ee2080b6-debb-43bf-8664-9a4c0f9fcf5f": {"__data__": {"id_": "ee2080b6-debb-43bf-8664-9a4c0f9fcf5f", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.20, para 2](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "40082223-c339-4726-9551-a64d35a3516a", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.20, para 2](https://elifesciences.org/articles/95402)"}, "hash": "0034a18564bb31abdff0408a97bab42dba4835aa1aa869e5b0474afac8175ebd", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### HERM HEAD", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 13, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c44b4b99-ce9d-4269-839c-7c968726768e": {"__data__": {"id_": "c44b4b99-ce9d-4269-839c-7c968726768e", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.20, para 3](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "89af665b-58cf-40fb-bfd1-7fa7b672090b", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.20, para 3](https://elifesciences.org/articles/95402)"}, "hash": "b4493618dfa7dae32ff6869482e32069e6b9a4c41326c03096527168e9d6faf2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "#### lateral view", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 17, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cd0faab2-ed7f-4951-b858-ef7767dfe4f0": {"__data__": {"id_": "cd0faab2-ed7f-4951-b858-ef7767dfe4f0", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.20, para 5](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ecc9fb2c-a8d4-4bb9-9283-d09d879ab3a4", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.20, para 5](https://elifesciences.org/articles/95402)"}, "hash": "66d498c88d6d06d1488cdbc137bb328433edb9e64309fa4eda993fbb6a0b35de", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### HERM MIDBODY", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 16, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "eee8d8dc-09e5-48bc-a69f-5dd79dd955fa": {"__data__": {"id_": "eee8d8dc-09e5-48bc-a69f-5dd79dd955fa", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.20, para 6](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7f92b1fa-5ba3-4491-8dd5-8bf320e1de29", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.20, para 6](https://elifesciences.org/articles/95402)"}, "hash": "4d53d5659dd5759e17d9713f521ac66e7f2854a826ec76a1d6b8f0efc210a657", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "#### lateral view", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 17, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f6bf3dfb-4b26-4611-9c70-bd0d3d468c69": {"__data__": {"id_": "f6bf3dfb-4b26-4611-9c70-bd0d3d468c69", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.20, para 8](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "95b3c9a0-24fd-46d7-bdc5-c39504eec8c7", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.20, para 8](https://elifesciences.org/articles/95402)"}, "hash": "9d94bd9da2059cab63229ee1cd48263fa1f15b64a49b577e9d01f2dae6a33580", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## B", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "eb04e5ef-a05b-4dfc-8c21-4728b53f0320": {"__data__": {"id_": "eb04e5ef-a05b-4dfc-8c21-4728b53f0320", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.20, para 9](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3df84232-090f-4399-b39d-95b5dc086881", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.20, para 9](https://elifesciences.org/articles/95402)"}, "hash": "b2496115db79e43f23f6875e184d0bda67c4829800404c6e7066bdba5cda8f4b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### HERM HEAD", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 13, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a7c16afd-36c1-4d46-bb05-d666d7343a16": {"__data__": {"id_": "a7c16afd-36c1-4d46-bb05-d666d7343a16", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.20, para 10](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f410e815-cafc-497d-a0d1-74f2846cabcd", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.20, para 10](https://elifesciences.org/articles/95402)"}, "hash": "02b604bf8b986bcab1acefd8864ba6ead4cb3acef8c1dc336c1068f48cc56147", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "#### lateral view", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 17, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e784cbbf-66b8-4569-926a-84df55529c28": {"__data__": {"id_": "e784cbbf-66b8-4569-926a-84df55529c28", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.20, para 12](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6fbc7129-6465-4dfb-bf5b-cdd287c400c1", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.20, para 12](https://elifesciences.org/articles/95402)"}, "hash": "0d65e28cac49de6f8eb8d5ee7c811c2a651c93bb12280aed32a07f60e1423de5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## C", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "88d53331-0141-4f66-8085-a2fdfc7b700e": {"__data__": {"id_": "88d53331-0141-4f66-8085-a2fdfc7b700e", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.20, para 13](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a9cf3d7e-c473-4d53-8f4e-6d14758e273e", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.20, para 13](https://elifesciences.org/articles/95402)"}, "hash": "15406fd41d226f614c0202e4c708ce6daed5a5b54e1d8ec9346101527b2e46a7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### HERM HEAD", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 13, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6c800101-b867-4c6e-9efd-3fb32484d607": {"__data__": {"id_": "6c800101-b867-4c6e-9efd-3fb32484d607", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.20, para 14](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f4668889-b6b2-4318-876c-4dff5cfd59de", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.20, para 14](https://elifesciences.org/articles/95402)"}, "hash": "f7e277dd1dddd72cc1d620d3e974edcefc353731b334687cef9d2ac55433f0f3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "#### lateral view", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 17, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "abf6ac69-b132-4430-b435-c4c63ed86f7b": {"__data__": {"id_": "abf6ac69-b132-4430-b435-c4c63ed86f7b", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.20, para 17](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "39e2a103-e949-4dd3-982f-22287a4b383c", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.20, para 17](https://elifesciences.org/articles/95402)"}, "hash": "5814c52573a8dfe0c6a27b34233a7f9816757b942a846aefa8f978f7a80c6b76", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Notably, four CAT-1/VMAT-expressing neuron classes, CAN, AUA, RIR, and ASI, do not express biosynthetic enzymes for synthesis or uptake transporters of the four conventional monoaminergic transmitters known to be employed in C. elegans (serotonin, dopamine, octopamine, or tyramine). Hence, these neuron classes might instead synthesize or uptake another transmitter for ensuing synaptic", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 387, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1b3c8186-41b7-4f8f-9e22-0e26b7f1e6cf": {"__data__": {"id_": "1b3c8186-41b7-4f8f-9e22-0e26b7f1e6cf", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.20, para 18](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0d02d444-1abf-4425-9cc6-29a7006e6474", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.20, para 18](https://elifesciences.org/articles/95402)"}, "hash": "262118adee67a67829bbda6c07f32b0e3f01163b3a9145de6c06b9ea41cdd379", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Wang et al. eLife 2024;13:RP95402. DOI: https://doi.org/10.7554/eLife.95402    20 of 46", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 87, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ebb0e485-4d93-4d8f-8f34-4c0cec26d9ce": {"__data__": {"id_": "ebb0e485-4d93-4d8f-8f34-4c0cec26d9ce", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 1](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ba10b879-84eb-4956-b93d-c91b1f05d4ea", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 1](https://elifesciences.org/articles/95402)"}, "hash": "6696458d8fff0b47db96a5520411b9baef31df8bd7866840e5793a323bd7e451", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# mod-5(vlc47\\[mod-5::t2a::mNeonGreen]) I", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 41, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2f3689ac-b39d-4076-b62c-6d752db752b6": {"__data__": {"id_": "2f3689ac-b39d-4076-b62c-6d752db752b6", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 2](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0412929a-54a9-44db-a5ef-1e16920503c5", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 2](https://elifesciences.org/articles/95402)"}, "hash": "35bef4a422e7c0b8c70c6a9cc3522a8d5ece643b393deca6903826df85dabbd9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## A", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a6827b44-91ae-446b-bd51-94b86737cffc": {"__data__": {"id_": "a6827b44-91ae-446b-bd51-94b86737cffc", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 3](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3ae95f1e-3802-4730-aca3-24dc3acae9b7", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 3](https://elifesciences.org/articles/95402)"}, "hash": "45fa4af7e8eae202617c658c12eb282da1e3b320e2bbab7bcb6e60c1c545182a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### mod-5^CRISPR ::mNG", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 22, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "89deeb04-75ed-4df1-a556-2a2c0125b296": {"__data__": {"id_": "89deeb04-75ed-4df1-a556-2a2c0125b296", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 4](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e5a9c8fa-9fd2-41ef-b0e5-9730442b75e2", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 4](https://elifesciences.org/articles/95402)"}, "hash": "ef127e6ec64d9d1ae5b455bf3fc414d4430c983a9771cc4eb95fdfc2bbd8c260", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### HERMAPHRODITE", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 17, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "07af788a-3b8a-43da-8011-d3820a92de5e": {"__data__": {"id_": "07af788a-3b8a-43da-8011-d3820a92de5e", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 5](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f1768659-36ed-490e-9fb9-dd962071bfac", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 5](https://elifesciences.org/articles/95402)"}, "hash": "5263620fb383a1b5028056c8530a2c1fe313f57f3a89014f99f7b50807daa3ce", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### NeuroPAL", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 12, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "92070e73-3b51-4d10-a9ac-67c9649c839c": {"__data__": {"id_": "92070e73-3b51-4d10-a9ac-67c9649c839c", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 6](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "28bd096e-f0cc-404b-8fce-991bb3643bc6", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 6](https://elifesciences.org/articles/95402)"}, "hash": "3bc5e829a6d4201fbd893b9f8243269a7eb18c8c9af0f6685425b2be5ab55bfd", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### MERGE", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 9, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ef1c57e2-b1f2-4081-8026-795304c6d7db": {"__data__": {"id_": "ef1c57e2-b1f2-4081-8026-795304c6d7db", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 7](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ebcd0e35-ae93-41a9-a758-89766c40b886", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 7](https://elifesciences.org/articles/95402)"}, "hash": "8963129b08c7edbe6958553ef6d0178185ef41d801bba8aa23bd669f799fa170", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* HEAD\n  * NSM\n  * ADF\n  * AIM\n  * RIH\n* single focal plane\n  * URX\n* TAIL\n  * PHA", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 82, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c5b95b95-636a-47f0-a6b3-afae2c76d6fe": {"__data__": {"id_": "c5b95b95-636a-47f0-a6b3-afae2c76d6fe", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 8](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e422645c-617c-4a7b-86e1-9896d4ab0aec", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 8](https://elifesciences.org/articles/95402)"}, "hash": "993bfa63f27a7abc33f52253e55a9b18d321a7b9bd1707b80c518633aba02e8c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## B", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6698a4ae-289d-4fc0-a651-99e0e0388bf3": {"__data__": {"id_": "6698a4ae-289d-4fc0-a651-99e0e0388bf3", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 9](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "45106a14-f6e8-4446-aeff-f51dea422dc2", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 9](https://elifesciences.org/articles/95402)"}, "hash": "e2a42d2d74b44bfa0e62dff82abb537c8e7bb1aaa8b21d39a9956fcb80c7c362", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### mod-5^CRISPR ::mNG", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 22, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "73e622e7-0853-433e-8485-2629d6cefe10": {"__data__": {"id_": "73e622e7-0853-433e-8485-2629d6cefe10", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 10](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9d1dde1c-0a20-4481-8300-35a6847ac013", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 10](https://elifesciences.org/articles/95402)"}, "hash": "f331687ab6cdbfc57023a25aebfc707df7c34bce6be4ed1c915079906b7bff68", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### MALE", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 8, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "bd02d555-52be-4b5c-b9bf-eb22be35edd2": {"__data__": {"id_": "bd02d555-52be-4b5c-b9bf-eb22be35edd2", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 11](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8eca7a7a-72b5-47fd-a162-b12e81a63173", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 11](https://elifesciences.org/articles/95402)"}, "hash": "09c58c6914758be1370ed9712e8b0bf65f9b7f7c0a0827af037be4ebda17dd25", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### NeuroPAL", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 12, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c1ac5bb1-b10a-4396-8e36-ceef36471d83": {"__data__": {"id_": "c1ac5bb1-b10a-4396-8e36-ceef36471d83", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 12](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "42df5c45-05d2-4705-b07d-37e29fd09642", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 12](https://elifesciences.org/articles/95402)"}, "hash": "ec4b99fb45a30a1967389f28f03438b5f0a18588b491e3dc1cf9ae23c529e387", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### MERGE", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 9, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "74c602f7-e7c7-4af8-a9c1-c83bde588fd5": {"__data__": {"id_": "74c602f7-e7c7-4af8-a9c1-c83bde588fd5", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 13](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "647e79d3-42b8-49ab-a7b9-8e956c8ea36d", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 13](https://elifesciences.org/articles/95402)"}, "hash": "bd22821671b5ce1dfd657dbdbaaccfdbf5310fd349cebd7de1e03ae62fc4e22a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* HEAD\n  * NSM\n  * CEMD\n  * AIM\n  * RIH\n  * CEMV\n* single focal plane\n  * URX\n* TAIL\n  * R9B(R/L)\n  * R3B\n  * PGA\n  * PHA", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 121, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b7264dfb-8a3c-4ced-9ef2-b6ea6a5e008b": {"__data__": {"id_": "b7264dfb-8a3c-4ced-9ef2-b6ea6a5e008b", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 14](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8efd6752-3fa2-4389-a51a-1fe952b1e856", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 14](https://elifesciences.org/articles/95402)"}, "hash": "57d1eeeaef31eb470be0f930798675ae7332d59b57dad3ff823399cf464af5f7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## C", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7021f1c0-1f74-4b7f-aa13-3e1ba943a93d": {"__data__": {"id_": "7021f1c0-1f74-4b7f-aa13-3e1ba943a93d", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 15](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1b213332-878e-4652-8a7f-8cd0a4a19de6", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 15](https://elifesciences.org/articles/95402)"}, "hash": "c4480928d92d659a191cd9077a568ab7771beca1a116aa0f3174a6daf051bf40", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### mod-5^CRISPR ::mNG", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 22, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "74b2729f-dc7c-4858-99c7-55a351fe0d04": {"__data__": {"id_": "74b2729f-dc7c-4858-99c7-55a351fe0d04", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 16](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ec0e2c0e-f01f-4163-ad2c-3888c265c9b1", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 16](https://elifesciences.org/articles/95402)"}, "hash": "549c22299747245a3796c73b363af5d26a3db3537dda49656290f1f177807627", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### VNC", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 7, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4c7fc0b9-9f0f-41c4-ae4f-72d6b6fce4dc": {"__data__": {"id_": "4c7fc0b9-9f0f-41c4-ae4f-72d6b6fce4dc", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 17](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6122a1b4-e67b-420f-9385-3dba391d3e82", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 17](https://elifesciences.org/articles/95402)"}, "hash": "550b31f46bb432107ee9e0426d1ef7645737435fb3a2dfc354e6b777ad6757ff", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### gut autofluorescence", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 24, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "13bf20c6-009b-4f3f-9785-bb2de3e92b34": {"__data__": {"id_": "13bf20c6-009b-4f3f-9785-bb2de3e92b34", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 18](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4df05557-774f-4a69-a657-9abb136521e7", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 18](https://elifesciences.org/articles/95402)"}, "hash": "50bce619136a5d955f7dd902f23393111f6555d2b613cd6eaf44106edb08ebf4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### MERGE with NeuroPAL", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 23, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2aaa3c4c-2a2f-45a6-9435-c7bbe60f36b1": {"__data__": {"id_": "2aaa3c4c-2a2f-45a6-9435-c7bbe60f36b1", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 19](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2881efd2-e94d-424f-a531-04b0080db945", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 19](https://elifesciences.org/articles/95402)"}, "hash": "da446314fd3ee58f1eaaf4de831f19150b56eeb5596921fdd9db18c176a60896", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## D", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "76f4c367-85e5-41ee-8fc7-2223e9b13240": {"__data__": {"id_": "76f4c367-85e5-41ee-8fc7-2223e9b13240", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 20](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "be89c6f5-1826-42c8-9352-bca92c8b30c2", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 20](https://elifesciences.org/articles/95402)"}, "hash": "baa0ba6d15a237ee0f079343d0f2bd8a414079ccd141e461356834dd98935839", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### mod-5^CRISPR ::mNG", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 22, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5775d581-b268-4177-b953-f7939e30bb37": {"__data__": {"id_": "5775d581-b268-4177-b953-f7939e30bb37", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 21](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "eebfa505-f4ee-465c-8d26-e22e865a3b5c", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 21](https://elifesciences.org/articles/95402)"}, "hash": "342586cbd875a04f318047f255ab63d6404c47cc24bc76cd9eba4f0eb40545fb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### VNC", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 7, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7267727d-d723-43d9-baa0-889b0f72323b": {"__data__": {"id_": "7267727d-d723-43d9-baa0-889b0f72323b", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 22](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b6f0e86c-88ed-44d6-b16c-1b90b16ed57a", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 22](https://elifesciences.org/articles/95402)"}, "hash": "c5902a86294d7896f967bae31b8de713a6ad2a64137948b9a2bc035da3ae9337", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### MERGE with NeuroPAL", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 23, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b38cfbf1-a638-447c-9a3c-06e3a72c4544": {"__data__": {"id_": "b38cfbf1-a638-447c-9a3c-06e3a72c4544", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 24](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e1b72a5c-8b1f-4f97-9992-7077d92589a2", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 24](https://elifesciences.org/articles/95402)"}, "hash": "640ca8180fd622c90b7f47bce6c8c8602e70812da2ebfe1bee3dd772953ceff4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## E", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f67c905d-7f8a-4786-8ccc-abbc4a851f74": {"__data__": {"id_": "f67c905d-7f8a-4786-8ccc-abbc4a851f74", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 25](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "39f53874-f8df-4bfc-a96a-ecbed3fb7674", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 25](https://elifesciences.org/articles/95402)"}, "hash": "4a6e176444044c4d0a293acf3127e399707b28840c84d1315cd6e95d58d65ea6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### mod-5^CRISPR ::mNG + DiD (for PHA & PHB)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 44, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "84553f6f-f28c-4b4e-b7b3-2a1b383c6325": {"__data__": {"id_": "84553f6f-f28c-4b4e-b7b3-2a1b383c6325", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 26](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d349f75f-3841-4fb1-b60c-c97389f98340", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 26](https://elifesciences.org/articles/95402)"}, "hash": "2f77e83f693d4aea4c071c4778406323316a72576160b8afaec9007b05cd9de2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* YOUNG ADULT HERM\n  * PHB\n  * PHA\n* YOUNG ADULT MALE\n  * PHB\n  * PHA\n* L4 MALE\n  * PHB\n  * PHA", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 95, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "13df00be-67c0-4656-85b8-288cb5fda83c": {"__data__": {"id_": "13df00be-67c0-4656-85b8-288cb5fda83c", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 27](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c1390252-642b-4637-8b9e-f8aa51b69ac0", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 27](https://elifesciences.org/articles/95402)"}, "hash": "70e08f8e9827d7a929375023fc44a7d2bd3c80981d006a0dc55eb0d3eaf4c0ec", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## F", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c7ded047-5c2e-4b62-8577-8f26795bab0a": {"__data__": {"id_": "c7ded047-5c2e-4b62-8577-8f26795bab0a", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 28](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f7083899-a36f-4f5e-91c1-41f2beb4b9a6", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 28](https://elifesciences.org/articles/95402)"}, "hash": "4d1fdf6158129656f7c224e7258d31730b4a5037de7db7b224cab99a14047b6c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### expression of reporter alleles in ADF", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 41, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "dd78f7d7-be29-4d36-a582-66fd87a02ec4": {"__data__": {"id_": "dd78f7d7-be29-4d36-a582-66fd87a02ec4", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 29](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8e7f3de3-7de4-43f0-8bc9-0af1a9f40a21", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 29](https://elifesciences.org/articles/95402)"}, "hash": "4402380da818d197e6d041198edaeda230d81425b423a0e844aeabc5fac79520", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* mod-5^CRISPR ::mNG\n  - mNG intensity (a.u.)\n  - HERM\n  - MALE\n  - ***\n* tph-1^CRISPR ::gfp\n  * GFP intensity (a.u.)\n  * HERM\n  * MALE\n  * n.s.\n* unc-17^CRISPR ::gfp\n  * GFP intensity (a.u.)\n  * HERM\n  * MALE\n  * n.s.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 218, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "02a27490-ae71-4463-a54e-804396bbdaae": {"__data__": {"id_": "02a27490-ae71-4463-a54e-804396bbdaae", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 30](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4bec65b1-7ce1-4dc0-a194-91850b146a79", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 30](https://elifesciences.org/articles/95402)"}, "hash": "b563577264f7c0a39fd2c2d58c10557274103116428ab311165933866be6d674", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## G", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2737941e-142f-4ec0-9960-0339034275f1": {"__data__": {"id_": "2737941e-142f-4ec0-9960-0339034275f1", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 31](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6ac19078-e298-4b9c-a550-1b99dc50d34f", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 31](https://elifesciences.org/articles/95402)"}, "hash": "eab185e451e7d4d19a22b9ee8409663ffa8f0ea52758de10c2b41faf9f1e08f7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### anti-5-HT immunostaining in the male tail", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 45, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0ef4913f-2602-4f45-97bd-c891f38129de": {"__data__": {"id_": "0ef4913f-2602-4f45-97bd-c891f38129de", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 32](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "52dd5a42-8032-4419-b31a-ac6b79ba83d0", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 32](https://elifesciences.org/articles/95402)"}, "hash": "852d26d505bc8670300676e429fe22843cd01d4e1f5015064addc58cdc37238b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* wild type\n  * CP5\n  * CP6\n  * R1B\n  * R3B\n  * PGA\n  * R9B\n* mod-5 mutant\n  * CP5\n  * CP6\n  * R1B\n  * R3B", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 106, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "be7d222b-845a-4baf-becc-45ab9eafef83": {"__data__": {"id_": "be7d222b-845a-4baf-becc-45ab9eafef83", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 33](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6b6d8e78-5312-421a-a9a1-0f20eaeda58d", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 33](https://elifesciences.org/articles/95402)"}, "hash": "7835d7bf0b6c949c58fcf07f7110802b00151642ef1125d462132fcae3551133", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# oct-1(syb8870\\[oct-1::sl2::gfp::h2b]) I", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 41, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7b106718-bcb5-4c4a-a2e6-2dc025330796": {"__data__": {"id_": "7b106718-bcb5-4c4a-a2e6-2dc025330796", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 34](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "95fe7e1e-b6cc-4bea-b093-583f5c4d6fc7", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 34](https://elifesciences.org/articles/95402)"}, "hash": "6d4c1208a12a2e950d7f2c4dfe0a01d34949a8580813b5cfd2b0b5c883042f7d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## H", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ad453b3c-77fc-47b2-bb14-4af0a10a1fdd": {"__data__": {"id_": "ad453b3c-77fc-47b2-bb14-4af0a10a1fdd", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 35](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1cdf64b6-d492-40c9-ac60-c782e13aaf01", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 35](https://elifesciences.org/articles/95402)"}, "hash": "8bac302f2570ad2b050e82c48b85892f4b3bf63242f8763ecdb08c40f93c8cfc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### oct-1^CRISPR ::gfp", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 22, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "40734343-3ab2-4ddf-b52d-3a927c0bb5be": {"__data__": {"id_": "40734343-3ab2-4ddf-b52d-3a927c0bb5be", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 36](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8fb39f44-017f-433f-8a21-ae314c4bdf6e", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 36](https://elifesciences.org/articles/95402)"}, "hash": "9916ae5042bc8c7fa1d3eeae8cedb9dcb6c1bba589256b70fd17ec4948949bd2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### HERMAPHRODITE", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 17, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0f842c91-10d0-4013-8d56-ea725bdc8655": {"__data__": {"id_": "0f842c91-10d0-4013-8d56-ea725bdc8655", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 37](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "18a2d554-42a7-469c-b136-61ca2a44649a", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 37](https://elifesciences.org/articles/95402)"}, "hash": "4036ee08d76c501192eb547318b76b781600e9360462d4d8c8cebb7eb8896957", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### NeuroPAL", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 12, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1b56b76d-b70b-46b4-b0e4-291b5bb44644": {"__data__": {"id_": "1b56b76d-b70b-46b4-b0e4-291b5bb44644", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 38](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "03267a68-fa4e-4b61-9e01-89fa1155cb91", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 38](https://elifesciences.org/articles/95402)"}, "hash": "87163c7f75e752f1197162ea7411de82e399cf10b4670dc6f642e08ea9927220", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### MERGE", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 9, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "62002b7a-26ff-4b65-89d7-708290339712": {"__data__": {"id_": "62002b7a-26ff-4b65-89d7-708290339712", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 40](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2f354f43-40d8-4720-88d0-e92fc76432af", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 40](https://elifesciences.org/articles/95402)"}, "hash": "94022a45b260aee7eb348ddf56e179c5c26e6693dd92b7e7921118db74140520", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## I", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d6e0729e-36f7-42e8-b570-b2df11a945e0": {"__data__": {"id_": "d6e0729e-36f7-42e8-b570-b2df11a945e0", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 41](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2cfcec01-b98b-4804-8bcb-e8f7b7bf3f33", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 41](https://elifesciences.org/articles/95402)"}, "hash": "f5b344bd6aeb459616d97650259f10100bc0cd79c8206b018bee83fcdb0b0965", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### oct-1^CRISPR ::gfp", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 22, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "abe369fb-84cf-4b7c-8050-cbfca110d33c": {"__data__": {"id_": "abe369fb-84cf-4b7c-8050-cbfca110d33c", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 42](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "17bc6656-bd15-4f73-bf62-75bd26937b2a", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 42](https://elifesciences.org/articles/95402)"}, "hash": "c8b987d6dee8668ad429e3a4f4f98b10d8445e1c16fc032cf408c4b3eb9d9cb8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### MALE", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 8, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f2fb2b59-519e-4af4-9130-fdcb6bbc338e": {"__data__": {"id_": "f2fb2b59-519e-4af4-9130-fdcb6bbc338e", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 43](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "12d18482-990e-4f5c-b742-03afd4470320", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 43](https://elifesciences.org/articles/95402)"}, "hash": "5d89239664cfc00bd7cce5bcd0d910532d778fdd9d85ac11cfe1287fed5f0375", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### NeuroPAL", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 12, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "770690da-ad9e-4d9d-b242-ae91996a7c7c": {"__data__": {"id_": "770690da-ad9e-4d9d-b242-ae91996a7c7c", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 44](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fa916fcc-2285-40a4-99e3-c4fa312fa74a", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 44](https://elifesciences.org/articles/95402)"}, "hash": "454af0df07b271f5dc4e7a31a667c932f8c9ecfd0c6a275deccb88f84eea70f7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### MERGE", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 9, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9ed79e89-71d0-456d-8b9d-86a264bc37d4": {"__data__": {"id_": "9ed79e89-71d0-456d-8b9d-86a264bc37d4", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 46](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9a2ef9ee-5dc4-43dc-9115-779b11441642", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 46](https://elifesciences.org/articles/95402)"}, "hash": "ea42b56e69018513f82a68a96126ef349b42f10602bd74b7fd04c23f625c68f1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## J", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5c505836-5740-4bef-af06-98042be515df": {"__data__": {"id_": "5c505836-5740-4bef-af06-98042be515df", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 47](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bfa3a9e6-1b4d-49ae-943b-6a012e3b7be7", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 47](https://elifesciences.org/articles/95402)"}, "hash": "429560644dd4c8e1e8e9e8e49b1b5f0330896c0f7c4e18041fc9890593d822d8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### HERMAPHRODITE", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 17, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "14f9dbbb-7377-4cd5-9323-ce5b3614d812": {"__data__": {"id_": "14f9dbbb-7377-4cd5-9323-ce5b3614d812", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 48](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "179019b6-06e6-4474-a5b3-8c039ad5af80", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 48](https://elifesciences.org/articles/95402)"}, "hash": "07ad9abc5379cc81d4da8e476bd6d81029529733eaba1b0d9e697e79487b2aa5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### MALE", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 8, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a768266c-6a4b-41fc-a2e6-ec00d4431d03": {"__data__": {"id_": "a768266c-6a4b-41fc-a2e6-ec00d4431d03", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 49](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "adabdeca-604c-41d7-a7f8-067b6d721732", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 49](https://elifesciences.org/articles/95402)"}, "hash": "ce57685e6060cbdf2029f160d92ed5896bb6c576f76aeb08541f096eaa69aa52", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* head\n  * (BWM throughout body)\n* tail\n  * (BWM throughout body)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 65, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6b888baf-b9ec-45ba-a4a9-c18c5f1922e1": {"__data__": {"id_": "6b888baf-b9ec-45ba-a4a9-c18c5f1922e1", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 50](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b4baed98-5cd8-410a-97f9-cc41c036d0cb", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 50](https://elifesciences.org/articles/95402)"}, "hash": "5f7dc6a7608f02f5e6d8170458d3a275ce5b48fe61f1e893dbc717e22d2e46f6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## K", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7c7e1a0e-50d7-4101-8fb9-f04d6d0e154f": {"__data__": {"id_": "7c7e1a0e-50d7-4101-8fb9-f04d6d0e154f", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 51](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8c786e60-e124-4cbd-b51a-6f23a395ea9f", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 51](https://elifesciences.org/articles/95402)"}, "hash": "a181bcb7d9d69c01c7304db207d732ea949eca4453c6cdf7a3cd7a5ab1937183", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### oct-1^CRISPR ::gfp merge with non-neuronal markers", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 54, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "585ab72d-42cc-47c5-b1de-affcb1f62eda": {"__data__": {"id_": "585ab72d-42cc-47c5-b1de-affcb1f62eda", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 52](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "40c27596-7387-4b6e-a7d0-9bd07fde3e77", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 52](https://elifesciences.org/articles/95402)"}, "hash": "8fb54c41b5cc975b03479db66939d79449ae29b525743f1f6556ecf67ad9c1c8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* HEAD\n  * merge with hypodermal marker\n    * oct-1^CRISPR ::gfp\n    * hyp\n    * hyp\n  * pan-glial marker\n    * ::gfp\n    * glia\n* MID\n  * ms\n  * ms\n* TAIL\n  * gonadal cells\n  * hyp\n  * gonadal cells\n  * hyp\n* MERGE\n  * glia", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 224, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "19f8c35b-16b8-4719-9ac8-afdb89b25fa4": {"__data__": {"id_": "19f8c35b-16b8-4719-9ac8-afdb89b25fa4", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 53](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ce396345-98a8-4e0b-95c6-923050043c40", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.21, para 53](https://elifesciences.org/articles/95402)"}, "hash": "675db8a312a6d9454832b7c558bddb0294a47eb74bb11a88894110fa211c671a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Figure 8. Expression of mod-5/SERT and oct-1/OCT reporter alleles in adult animals. Neuronal expression was characterized with landmark strain NeuroPAL (otIs669) and DiD-filling. (A, C) In adult hermaphrodites, mod-5(vlc47) is expressed in sex-shared neurons NSM, ADF, RIH, AIM, consistent with previous reports (Jafari et al., 2011; Maicas et al., 2021). In addition, we also observed expression in the phasmid neuron PHA and dim and variable expression in URX. There is no visible expression in the ventral nerve cord (VNC). (B, D) In adult males, mod-5(vlc47) is visibly expressed in NSM, RIH, AIM, as well as the male-specific neurons CEM, PGA, R3B, R9B, and CP1 to CP6. Expression in ADF is often not detected (see F). (E) DiD-filling confirms mod-5(vlc47) expression in phasmid neuron class PHA, and not PHB, in young adults in both sexes (L4 male image is to facilitate neuron ID in Figure 8 continued on next page", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 921, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a4c51962-3f24-4dce-b8d6-eed2225d7eec": {"__data__": {"id_": "a4c51962-3f24-4dce-b8d6-eed2225d7eec", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.22, para 0](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "db072505-1cf1-4b03-8ac3-0ad8093885c8", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.22, para 0](https://elifesciences.org/articles/95402)"}, "hash": "f965119dde9e0b0f0cbcdedeca781ea572929ce3a61b56ccb466823c874c84d0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# eLife Tools and resources", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 27, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ebd5da03-f124-43ec-bb9f-649b3b345120": {"__data__": {"id_": "ebd5da03-f124-43ec-bb9f-649b3b345120", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.22, para 3](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "648ef583-ff0d-45e4-b409-9bc4bbd5ecf7", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.22, para 3](https://elifesciences.org/articles/95402)"}, "hash": "47edbd2a6f991de6650a1dcca8068e5320ce3dbadf5f572d1b4cf137a242ba46", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "adults, because the positions of the two neuron classes can change in males during the L4 to adult transition). (F) Expression of mod-5(vlc47) in ADF is stronger in hermaphrodites than in males. Each dot represents a single animal. Expression is not sexually dimorphic for the reporter alleles of either the serotonin-synthesizing enzyme `tph-1` or the vesicular acetylcholine transporter `unc-17`. Expression was normalized against expression in other reporter-expressing neurons. Statistics, Mann-Whitney test. (G) In the tail region of wild type males, male-specific neurons PGA, R1B, R3B, and R9B are stained positive for serotonin. In a mod-5(n3314) mutant background, staining is completely lost in PGA (41/41 stained animals) and significantly affected for R9B (completely lost in 31/41 animals and much dimmer in the rest), while it remains in all 41 stained animals for R1B and R3B. The staining for CP1 to CP6 are also not affected in mod-5 mutant animals (remaining in 41/41 stained animals; image showing CP5 and CP6). (H, I) In adult animals, oct-1(syb8870) is expressed in the tyraminergic neuron class RIM in both sexes. Expression is not observed in any other neurons. (J, K) Outside the nervous system, oct-1(syb8870) is expressed in body wall muscle (BWM) throughout the worm (J) as well as hypodermal cells and selected head glia (K). Expression is also observed in gonadal cells in the male vas deferens (K). A pan-glial reporter `otIs870[mir-228p::3xnls::TagRFP]` and a `dpy-7p::mCherry` reporter `stIs10166 [dpy-7p::his-24::mCherry+unc-119(+)]` were used for glial and hypodermal identification, respectively. Scale bars, 10 \u00b5m.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1650, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0344dd80-4100-45b4-83b6-33cb8613710a": {"__data__": {"id_": "0344dd80-4100-45b4-83b6-33cb8613710a", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.22, para 4](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "48be0574-3789-4d20-83ca-baa7d35543a7", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.22, para 4](https://elifesciences.org/articles/95402)"}, "hash": "b5e4cde67fd76aa0dacc5630a558380c57a208d52951da13db8a2f3abbe2f79b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "release via CAT-1/VMAT. We considered the putative neurotransmitter betaine as a possible candidate, since CAT-1/VMAT is also able to package betaine (`Peden et al., 2013; Hardege et al., 2022`). Betaine is synthesized endogenously, within the nervous system mostly in the cat-1/VMAT-positive RIM neuron (`Hardege et al., 2022`), but it is also available in the bacterial diet of *C. elegans* (`Peden et al., 2013`). In vertebrates, dietary betaine is taken up by the betaine transporter BGT1 (aka SLC6A12). To test whether cat-1/VMAT-positive neurons may acquire betaine via BGT1-mediated uptake, we CRISPR/Cas9-engineered a reporter allele for `snf-3/BGT1`, `syb7290`. We detected expression in the betaine-synthesizing (and also tyraminergic) RIM neuron (Figure 9, Tables 1 and 2). In addition, `snf-3` is indeed expressed in all the four cat-1/VMAT-positive neuron classes that do not synthesize a previously known monoaminergic transmitter (CAN, AUA, and variably, RIR and ASI) (Figure 9A and B). These neurons may therefore take up betaine and synaptically release it via CAT-1/VMAT. The `snf-3(syb7290)` reporter allele is also expressed in the serotonergic neuron NSM (albeit variably) (Tables 1 and 2), thus NSM could also be a betaine uptake neuron. In addition, we also detected `snf-3(syb7290)` expression in several other neurons that do not express `cat-1(syb6486)` (Supplementary file 1). Expression was also observed in a substantial number of non-neuronal cell types (Figure 9E\u2013G, Table 2, Supplementary file 1). These neurons and non-neuronal cells may serve to clear betaine (see Discussion, Neurotransmitter synthesis versus uptake). `snf-3(syb7290)` is not expressed in the inner and outer labial neuron classes as previously suggested (`Peden et al., 2013`); these cells were likely misidentified in the previous study and are in fact inner and outer labial glial cells (as discussed further below).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1921, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1c7e77ae-28c4-4501-9e03-cb100e238328": {"__data__": {"id_": "1c7e77ae-28c4-4501-9e03-cb100e238328", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.22, para 5](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "32a74f8e-1ef8-4b86-9e69-16cead773455", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.22, para 5](https://elifesciences.org/articles/95402)"}, "hash": "cbd06fee8e7ec191bc1e86ad7c44d929d004553dfca90f58b6ad16c54effab29", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Together with the expression pattern of the uptake transporters, all cat-1/VMAT-positive neurons in the hermaphrodite can be matched with an aminergic neurotransmitter. We nevertheless wondered whether another presently unknown monoaminergic transmitter, e.g., histamine or other trace amine, could be synthesized by a previously uncharacterized AAAD enzyme encoded in the *C. elegans* genome, `hdl-1` (Figure 1\u2014figure supplement 1A; `Hare and Loer, 2004`). We CRISPR/Cas9-engineered an `hdl-1` reporter allele, `syb1048`, but detected no expression of this reporter in the animal (Figure 1\u2014figure supplement 1C and D). Attempts to amplify weak expression signals by insertion of Cre recombinase into the locus failed \\[`hdl-1(syb4208)`] (see Materials and methods). CeNGEN scRNA data also shows no strong transcript expression in the hermaphrodite nervous system and only detected notable expression in sperm (`Taylor et al., 2021`).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 934, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "56a257c2-615c-4b90-b15d-d067028dac51": {"__data__": {"id_": "56a257c2-615c-4b90-b15d-d067028dac51", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.22, para 6](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c711a45e-6e1a-499c-a3aa-7a51db5d4948", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.22, para 6](https://elifesciences.org/articles/95402)"}, "hash": "5f9080314d374fde6fdfb465d93eba23f4d2437a3df24db63326f606cf97e6cc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Reporter alleles and NeuroPAL-facilitated neuron class-identification reveal novel expression patterns of neurotransmitters in the male-specific nervous system", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 162, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "11f9b52a-c1a8-4f7f-8189-ea70422db420": {"__data__": {"id_": "11f9b52a-c1a8-4f7f-8189-ea70422db420", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.22, para 7](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e2fad348-b6e9-4c23-ad7a-6a7110b1eafe", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.22, para 7](https://elifesciences.org/articles/95402)"}, "hash": "b8c866d5bfd3f070b9f5ca2a1a29ada1693df0f528ff48d4f0078fdc4cfe0921", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "No comprehensive scRNA atlas has yet been reported for the nervous system of the male. Based on the expression of fosmid-based reporters, we had previously assembled a neurotransmitter atlas of the *C. elegans* male nervous system in which individual neuron classes are notoriously difficult to identify (`Serrano-Saiz et al., 2017b`). We have since established a NeuroPAL landmark strain that permits more reliable identification of gene expression patterns in both the hermaphrodite and male-specific nervous system (`Tekieli et al., 2021; Yemini et al., 2021`). We used NeuroPAL to facilitate the analysis of the expression profiles of our CRISPR/Cas9-engineered reporter alleles in the male, resulting in updated expression profiles for 11 of the 16 knock-in reporter alleles analyzed. As in the hermaphrodite, reasons for these updates vary. In addition to the improved accuracy of neuron identification", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 908, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1dc14136-0977-4b8e-894e-efb099c1c043": {"__data__": {"id_": "1dc14136-0977-4b8e-894e-efb099c1c043", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.23, para 0](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "834ef333-3672-43c1-b904-a3b42788cb7a", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.23, para 0](https://elifesciences.org/articles/95402)"}, "hash": "c7f8dc3164168dea5b382a1b5f0b92ac414deeb0207e1c04c6150697b7611b4a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# snf-3(syb7290\\[snf-3::tagRFP::sl2::gfp::h2b]) II", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 50, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "171ba175-64a7-4040-beca-4057f202f647": {"__data__": {"id_": "171ba175-64a7-4040-beca-4057f202f647", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.23, para 1](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b09986a2-5ff2-448f-a44b-550223a5ecbf", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.23, para 1](https://elifesciences.org/articles/95402)"}, "hash": "5060962b829bbc6be24da82ee2cf41f0fcd9eb936b7690477ef5d0a46c93897e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## HERMAPHRODITE", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 16, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e79390cf-8e7d-42a6-bf02-8621864e65af": {"__data__": {"id_": "e79390cf-8e7d-42a6-bf02-8621864e65af", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.23, para 2](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "834dfd5a-f3cb-4bca-af49-2e5b6492f2c2", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.23, para 2](https://elifesciences.org/articles/95402)"}, "hash": "a17583854cfe2ef21e987b7055fd783e0ef3dc02bbb92a6477748a64c90e6f5d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### A", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 5, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8a554336-102c-49df-a9ba-81cd20bcbbad": {"__data__": {"id_": "8a554336-102c-49df-a9ba-81cd20bcbbad", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.23, para 3](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "65e2b762-40e9-4922-8afe-64fb98c0e198", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.23, para 3](https://elifesciences.org/articles/95402)"}, "hash": "7e0f1f0be3e97e3027af67e9b05b66584348ac5f9a0dc9b40d9c5d4f58610a62", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* **snf-3^CRISPR ::gfp NeuroPAL MERGE**\n  * **HEAD**\n    * AIB\n    * RIM\n    * AUA\n  * **TAIL**\n    * RIR\n    * RMH\n    * SMD\n* **snf-3^CRISPR ::gfp DiD MERGE**\n  * ASI (+/-)\n* **snf-3^CRISPR ::gfp NeuroPAL MERGE**\n  * VA12\n  * PDA\n  * DA9\n  * PVN\n  * PHC", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 255, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7c7d8295-9aa1-4c0c-bf59-6f616145fbbe": {"__data__": {"id_": "7c7d8295-9aa1-4c0c-bf59-6f616145fbbe", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.23, para 4](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "740601bf-6130-4f71-9d85-44901bbccc0a", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.23, para 4](https://elifesciences.org/articles/95402)"}, "hash": "c5f1f72b9bc24c5f2a0e18d936fec689ac4bb7b70b6b7e35b1086d6d7967d3e7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## B", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "22720614-5ce6-4a10-9c8f-2da407b6067b": {"__data__": {"id_": "22720614-5ce6-4a10-9c8f-2da407b6067b", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.23, para 6](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0e6d2aa1-ea60-444a-8783-7579513b04d7", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.23, para 6](https://elifesciences.org/articles/95402)"}, "hash": "e213ee9162f806992152ae5b3a2d6cb875ad26e61407f0a631eb65c282fdd18a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## C", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e503a99d-7d78-4958-a3da-824ecb6ecda0": {"__data__": {"id_": "e503a99d-7d78-4958-a3da-824ecb6ecda0", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.23, para 7](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1d49103a-926a-4938-b3aa-499acd3dcccb", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.23, para 7](https://elifesciences.org/articles/95402)"}, "hash": "dc471f8bb8749d69b3a044825e7c9620dae55d36677b8c65a56a4fec8d262e94", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* **snf-3^CRISPR ::gfp NeuroPAL MERGE**\n  * **TAIL**\n    * PDA\n    * DA9\n    * PDC\n    * VA12\n    * PVV\n    * PVX\n    * (-)\n    * DVB\n    * PHD\n    * PVN\n    * PHC", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 163, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3334cacc-8806-40d0-8f78-3d522ec9a3ac": {"__data__": {"id_": "3334cacc-8806-40d0-8f78-3d522ec9a3ac", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.23, para 8](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e50dd9fe-3a1c-49ce-98bf-318ec0979c65", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.23, para 8](https://elifesciences.org/articles/95402)"}, "hash": "6595014c36be444c40911e886fdc85110bc60c5aa8f13beb2a1d1a9d9902c518", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## MALE", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 7, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e694d896-be54-4e29-a708-398548158b79": {"__data__": {"id_": "e694d896-be54-4e29-a708-398548158b79", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.23, para 9](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "92f932f3-7084-48f1-8986-ed6a703407d1", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.23, para 9](https://elifesciences.org/articles/95402)"}, "hash": "c2cf72e7540fab7608a7d542e7d2246f2104cfb8b06051410445dec8612175e1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### D", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 5, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "75a437f4-1e6e-4234-8b52-46fadb12a6ec": {"__data__": {"id_": "75a437f4-1e6e-4234-8b52-46fadb12a6ec", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.23, para 10](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e0255b6e-49bf-4ce6-8543-ce94caf2e9ae", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.23, para 10](https://elifesciences.org/articles/95402)"}, "hash": "a0e26295cec4822a99eac255dbafee8628ccbeee30a66982f1f7a9530735fdd1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* **snf-3^CRISPR ::gfp**\n  * **MIDBODY**\n    * CAN\n    * PDEso/sh\n    * PDE (no snf-3)\n* **snf-3^CRISPR ::gfp + NeuroPAL**", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 122, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "db0ebc22-d836-4cfe-84f5-e62178834d7c": {"__data__": {"id_": "db0ebc22-d836-4cfe-84f5-e62178834d7c", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.23, para 11](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f6809d20-8dc2-4eec-b8a3-509959fb2ca6", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.23, para 11](https://elifesciences.org/articles/95402)"}, "hash": "8d79723ef0dffe9e06acc07670bf366d750eaf731c506e7ca3c28fe664174bda", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## E", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "35cc5035-427d-4a39-b253-dfb583763bfb": {"__data__": {"id_": "35cc5035-427d-4a39-b253-dfb583763bfb", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.23, para 12](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bd96584b-06be-40a3-87a5-cd3ec4c820b6", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.23, para 12](https://elifesciences.org/articles/95402)"}, "hash": "b00baddcf417c4e8c78cb43c9eec50fb84fac9b58b6a729449191dfe6de63f2a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* **snf-3^CRISPR ::gfp**\n  * **TAIL**\n    * SPso/sh\n    * somatic gonad\n    * dorsal view\n    * ventral view", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 108, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "abdd78c2-1f7b-4036-b35b-f0551b6d9043": {"__data__": {"id_": "abdd78c2-1f7b-4036-b35b-f0551b6d9043", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.23, para 13](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4770daf7-fc52-4e0f-970d-14b07f096818", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.23, para 13](https://elifesciences.org/articles/95402)"}, "hash": "84dc12b3ddcfe63310f56c573c897ab079d06859def3f1249e31a7998bfebd2d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## F", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "29f33c19-36e0-4669-a82f-f1aa646723f3": {"__data__": {"id_": "29f33c19-36e0-4669-a82f-f1aa646723f3", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.23, para 14](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9052010c-9c0a-49d9-bf6d-f11f3c877304", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.23, para 14](https://elifesciences.org/articles/95402)"}, "hash": "d24ff77dbcbc10e01f572b148ba550b360d37fb44a01d060014bf22c2a5e6d32", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* **HERM HEAD**\n  * glia\n* **HERM TAIL**\n  * hyp\n  * glia\n  * hyp\n* **MALE TAIL**\n  * glia\n  * hyp\n  * glia\n* **pan-neuronal snf-3^CRISPR ::gfp**\n  * **MERGE**\n    * (no overlap)\n    * (no overlap)\n    * (no overlap)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 216, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c2fbfe3d-0920-4f9d-854b-5796f963d746": {"__data__": {"id_": "c2fbfe3d-0920-4f9d-854b-5796f963d746", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.23, para 15](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8c3a4abd-28ff-4028-95e9-ca29dae340bf", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.23, para 15](https://elifesciences.org/articles/95402)"}, "hash": "15f4ba5273abfa0fab6b4aeedabe567918a0351b61ebf8887f9611d58146be76", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## G", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c442eacc-6173-4bdc-8e3e-061a5e694f1d": {"__data__": {"id_": "c442eacc-6173-4bdc-8e3e-061a5e694f1d", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.23, para 16](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "739e66e6-08b6-4302-b1f4-94bda3f41a71", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.23, para 16](https://elifesciences.org/articles/95402)"}, "hash": "d68defc1d6b2ec8e9146a2c9238408375fa2606fec0a1328c5621ee563653535", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* **HERMAPHRODITE**\n  * hypodermal and seam cells\n* **MALE**\n  * hypodermal and seam cells", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 90, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9d7dd077-23ea-4e1d-99aa-b7edc4c85157": {"__data__": {"id_": "9d7dd077-23ea-4e1d-99aa-b7edc4c85157", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.23, para 17](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7d0c1b2e-0682-4bf4-b535-7ba81f129e46", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.23, para 17](https://elifesciences.org/articles/95402)"}, "hash": "603a16a1298957ffd9a94a7a605554297d183c847edeb44b61e1f1584314645d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Cell type|Expression in hermaphrodite|Expression in male|\n|-|-|-|\n|AIB|+|+|\n|RIM|+|+|\n|AUA|+|+|\n|CAN|+|+|\n|RIR|+|+|\n|RMH|+|+|\n|SMD|+|+|\n|VA12|+|+|\n|DA9|+|+|\n|PDA|+|+|\n|PHC|+|+|\n|PVN|+|+|\n|DiD|+|+|\n|PDE|-|-|\n|PDC|-|+|\n|PHD|-|+|\n|PVV|-|+|", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 237, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b556a387-fd0b-48e9-bfc1-38ba16b904bd": {"__data__": {"id_": "b556a387-fd0b-48e9-bfc1-38ba16b904bd", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.23, para 18](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b2689249-e6cd-4fe2-8792-9379c758195c", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.23, para 18](https://elifesciences.org/articles/95402)"}, "hash": "de70406dc5ff659d097a7e992019f90496ad8931367a39770de590cdbaf8c45c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Figure 9.** Expression of *snf-3/BGT1/SLC6A12* in adult animals. Neuronal expression was characterized with landmark strain NeuroPAL (*otIs669*) and DiD-filling. (A, B) In the adult hermaphrodite, neuronal expression of *snf-3(syb7290)* is detected in cat-1/VMAT-positive neurons AUA, CAN, and dimly and variably, RIR and ASI (confirmed with DiD-filling). In addition, it is also expressed in cat-1/VMAT-negative neurons AIB, RIM, RMH, SMD, VA12, DA9, PDA, PHC, PVN as labeled, as well as more neurons listed in *Supplementary file 1*. In the midbody, expression is not detected in PDE (dopaminergic, cat-1-positive) but is in its associated glial cells. It is also detected in multiple vulval support cells (B) and some epithelial cells near the somatic gonad. (C) In the adult male, in addition to its expression in sex-shared neurons as in hermaphrodites, *snf-3(syb7290)* is also expressed in male-specific neuron class PDC, as well as in PHD and variably in PVV. (D) Similarly to its expression in hermaphrodites, *snf-3(syb7290)* is detected in CAN and PDE-associated glial cells, but not PDE neurons, in males. (E) In the male tail, *snf-3(syb7290)* is expressed in a number of glial cells including the spicule sockets and/or sheath cells (dorsal view). It is also detected in the somatic gonad (ventral view). (F) *snf-3(syb7290)* is broadly expressed in most if not all glia in both sexes. Glial cell type is determined by cell location and the appearance of their nuclei in Normarski. To confirm they are not neurons, a pan-neuronal marker (UPN, or 'uber pan-neuronal', a component in NeuroPAL) is used to determine non-overlapping signals between the two reporters. Head expression in Figure 9 continued on next page", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1730, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4eb9b352-9e45-4938-8ebc-f8eadfe79e93": {"__data__": {"id_": "4eb9b352-9e45-4938-8ebc-f8eadfe79e93", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.24, para 1](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2e887075-cebb-4722-92a1-2fa25e6277a9", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.24, para 1](https://elifesciences.org/articles/95402)"}, "hash": "ab09a7f886c4d1bb48bd094ee79381b92783ecd5ab316d8074787c59a5249bac", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Figure 9 continued\nthe male is very similar to that in the hermaphrodite and thus not shown. (G) snf-3(syb7290) is broadly expressed in hypodermal and seam cells in both sexes. Scale bars, 10 \u00b5m. Asterisks, non-neuronal expression.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 231, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "73a98c82-85c3-40c5-af75-6fb693611000": {"__data__": {"id_": "73a98c82-85c3-40c5-af75-6fb693611000", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.24, para 2](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e2fd7066-d37f-41ff-9a41-185fae8b1b9e", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.24, para 2](https://elifesciences.org/articles/95402)"}, "hash": "ad791f3877852405fbd3ac617b85a5dfa0e886a73b9d28098d6818a6380cd0c3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "provided by NeuroPAL, in some cases there are true differences of expression patterns between the fosmid-based reporters and reporter alleles. We elaborate on these updates for individual reporter alleles below.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 211, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e6fd0254-0cdd-4915-9b74-df6e6f6cc14c": {"__data__": {"id_": "e6fd0254-0cdd-4915-9b74-df6e6f6cc14c", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.24, para 3](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "070fdb12-ee81-40e4-87f2-1d4153793d5f", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.24, para 3](https://elifesciences.org/articles/95402)"}, "hash": "80b95631aa3351123a1e9cfd423cb69225e51fc4d3290a2d1da48cbd9429e382", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Expression of reporter alleles of Glu/ACh/GABA markers in the male-specific nervous system", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 93, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fa819376-35c0-4f5d-816b-20210856094c": {"__data__": {"id_": "fa819376-35c0-4f5d-816b-20210856094c", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.24, para 4](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "abb9ec22-4ac1-47b5-9a59-abe804f99d40", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.24, para 4](https://elifesciences.org/articles/95402)"}, "hash": "2eb751aa2f1df2e9ab2d32e04661e8b3af6caf40478249356e1391f1018679d4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We analyzed eat-4/VGLUT (syb4257), unc-17/VAChT (syb4491), unc-25/GAD (ot1372), and unc-47/VGAT (syb7566) expression in the male-specific nervous system using NeuroPAL landmark strains (otIs696 for eat-4 and otIs669 for all others)(Figures 10 and 11). Of all those reporter alleles, unc-25/GAD (ot1372) was the only one with no updated expression. Specifically, in addition to confirming presence of expression of the unc-25(ot1372) reporter allele in CP9, EF1/2, EF3/4, we also confirmed its lack of expression in anti-GABA-positive neurons R2A, R6A, and R9B (Gendrel et al., 2016; Serrano-Saiz et al., 2017b; Figure 11A, Supplementary file 3).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 645, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a9b4a8c9-eb3b-4719-91fa-2a1dbf4a7bda": {"__data__": {"id_": "a9b4a8c9-eb3b-4719-91fa-2a1dbf4a7bda", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.24, para 5](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "66036441-86ac-44c9-8666-d34d85906b59", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.24, para 5](https://elifesciences.org/articles/95402)"}, "hash": "39bbac751b38ca644fb3f85d630e082ca1bcf25019cef23a68dc251ec58af5a6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In the preanal ganglion, we observed weak expression of unc-17(syb4491) in DX3/4 (Figure 10B, Supplementary file 3), hence assigning previously unknown neurotransmitter identity to these neurons. Related to DX3/4, we also confirmed expression of unc-17 in DX1/2 in the dorsorectal ganglion, consistent with fosmid-based reporter data (Supplementary file 3; Serrano-Saiz et al., 2017b). In the lumbar ganglion, we detected novel expression of unc-17(syb4491) in five pairs of type B ray neurons, namely R1B, R4B, R5B, R7B, and R9B (Figure 10B, Supplementary file 3). Expression in all these neurons is low, possibly explaining why it is not observed with an unc-17 fosmid-based reporter (Serrano-Saiz et al., 2017b).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 715, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "60d0c4f9-7407-4f45-8384-e044b9ad0e0d": {"__data__": {"id_": "60d0c4f9-7407-4f45-8384-e044b9ad0e0d", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.24, para 6](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fac76b7a-556b-4074-8b0b-1e7860ea9d28", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.24, para 6](https://elifesciences.org/articles/95402)"}, "hash": "dff23d62ef297e1b082e8eff2b479269370e25cfa98989672febf3544992f01b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In the ventral nerve cord, we found additional, very weak expression of eat-4(syb4257) in CA1 to CA4 (Figure 10A, Supplementary file 3), as well as weak expression of unc-17(syb4491) in CP1 to CP4 (Figure 10B, Supplementary file 3), all undetected by previous analysis of fosmid-based reporters (Serrano-Saiz et al., 2017b). Conversely, two neurons lack previously reported expression of fosmid-based reporters; CP9 does not show visible unc-17(syb4491) expression (Figure 10B) and neither does CA9 show visible expression of unc-47(syb7566) expression (Figure 11C). We also realized that the neuron identifications of CA7 and CP7 were previously switched (Serrano-Saiz et al., 2017b), due to lack of proper markers for those two neurons. With NeuroPAL, we are now able to clearly distinguish the two and update their classic neurotransmitter reporter expression: CA7 expresses high levels of eat-4(syb4257) (Figure 10A, Supplementary file 3), very low levels of unc-17(syb4491) (Figure 10B), and no unc-47(syb7566) (Figure 11C); CP7 expresses no eat-4(syb4257) (Figure 10A, Supplementary file 3), very low levels of unc-17(syb4491) (Figure 10B), and very low levels of unc-47(syb7566) as well (Figure 11C). Taken together, the analysis of reporter alleles reveals a remarkable diversity of CA and CP neurons, summarized in Figure 10C.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1335, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5d071c4d-47c1-4236-b095-4f5aaea1136d": {"__data__": {"id_": "5d071c4d-47c1-4236-b095-4f5aaea1136d", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.24, para 7](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "68344a3a-034d-4d83-8688-bbf7c8fc6804", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.24, para 7](https://elifesciences.org/articles/95402)"}, "hash": "993b770850b5c46ab3f3c7722d218016c6d7be81f5caee5eda3d19ed9128a157", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In the head, we detected expression of unc-47(syb7566) in the male-specific neuron class MCM (Figure 11B, Supplementary file 3), previously not observed with fosmid-based reporters. Consistent with fosmid-based reporter data, the other male-specific head neuron class, CEM, shows expression of unc-17(syb4491) (Supplementary file 3) and unc-47(syb7566) (Figure 11B, Supplementary file 3) reporter alleles.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 405, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "04895fe3-d042-426f-a4fd-18c5cbcb1522": {"__data__": {"id_": "04895fe3-d042-426f-a4fd-18c5cbcb1522", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.24, para 8](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "72dba314-0fe8-436f-9861-c25a0bb5e06b", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.24, para 8](https://elifesciences.org/articles/95402)"}, "hash": "e6c98fc8ee71b64e965330ae67a2b3c7c0b8bc52a369c7052efb050107fa22ec", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Expression of reporter alleles for monoaminergic neurotransmitter pathway genes in the male-specific nervous system", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 118, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "48128278-8cc6-44ed-9a8a-c05d193395b2": {"__data__": {"id_": "48128278-8cc6-44ed-9a8a-c05d193395b2", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.24, para 9](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c42d55b3-20fc-4d64-b0fb-7512b4597046", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.24, para 9](https://elifesciences.org/articles/95402)"}, "hash": "8f660a1842bc278ede4ac61a226227d9ccfda7f6d311b2b9936e1a31ba960996", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We analyzed the expression of reporter alleles for genes involved in monoamine biosynthesis and uptake in the male-specific nervous system: cat-1/VMAT (syb6486), tph-1/TPH (syb6451), cat-2/TH (syb8255), bas-1/AAAD (syb5923), tdc-1/TDC (syb7768), tbh-1/TBH (syb7786), mod-5/SERT (vlc47), oct-1/OCT (syb8870), and snf-3/BGT1 (syb7290). As in the hermaphrodite nervous system, we used the NeuroPAL reporter landmark (otIs669) for neuron ID (Tekieli et al., 2021). We found novel expression patterns in all male-specific ganglia (Figures 12 and 13, Supplementary file 3).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 567, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b60d8629-ebe2-45a1-a646-2a74d9bc0382": {"__data__": {"id_": "b60d8629-ebe2-45a1-a646-2a74d9bc0382", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.25, para 0](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "581685d1-398f-48d2-94c1-8477bcb59883", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.25, para 0](https://elifesciences.org/articles/95402)"}, "hash": "3fa12b5e8401cf8f73e8e2235e24a860c30fd993de40df2d04785b2f613c8007", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Figure 10. Expression of eat-4/VGLUT and unc-17/VAChT reporter alleles in the adult male. Neuronal expression of eat-4(syb4257) and unc-17(syb4491) was characterized with landmark strain NeuroPAL (otIs696 and otIs669, respectively). Only selected neurons are shown to illustrate updates from previous studies. See Supplementary file 3 for a complete list of neurons. (A) eat-4(syb4257) expression. Top, long panels: CA1, CA2, and CA3 show", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 440, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a59d7877-8700-4777-930a-92c58591d0eb": {"__data__": {"id_": "a59d7877-8700-4777-930a-92c58591d0eb", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.25, para 1](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "645048dc-9650-44cc-953f-8228068b07b9", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.25, para 1](https://elifesciences.org/articles/95402)"}, "hash": "8af35f292a8b1367b0ed720a6b534006a4d2f52678cc6b54d336608eb9a5eaf1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## A", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c69d2bfe-4615-4a72-a30d-eafe9e945ba3": {"__data__": {"id_": "c69d2bfe-4615-4a72-a30d-eafe9e945ba3", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.25, para 2](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e8e80f97-a686-4f14-a5c9-5248977af819", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.25, para 2](https://elifesciences.org/articles/95402)"}, "hash": "c0635725c03901fad818a316ab012b005e559c3d93a6f77e87fae34890c6df80", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### MALE VENTRAL NERVE CORD", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 27, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "21757227-b7a6-4beb-949a-66072ab63dad": {"__data__": {"id_": "21757227-b7a6-4beb-949a-66072ab63dad", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.25, para 3](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5248fddc-ff3e-415e-a8a8-ee736d6ca828", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.25, para 3](https://elifesciences.org/articles/95402)"}, "hash": "25664eac8ef84a618018845c9f988fd0cab8023b67cd4fe830cb7062bc2b79cb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* **ventral view**\n  * eat-4^CRISPR ::gfp\n  * NeuroPAL\n  * MERGE\n* **CA1**\n* **CA2**\n* **CA3**", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 94, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1ed26fdf-d30f-42b4-982d-7133290ebf86": {"__data__": {"id_": "1ed26fdf-d30f-42b4-982d-7133290ebf86", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.25, para 4](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "85a70665-7252-4c8c-ac39-cbc20e3d8613", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.25, para 4](https://elifesciences.org/articles/95402)"}, "hash": "cb7c9833e754ddb640cdd23555f1d5d8ec3fb4bff60bb7be4bee20bb1cd615d7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## B", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b3205473-bd37-4eea-a3f2-b84cbb5274f3": {"__data__": {"id_": "b3205473-bd37-4eea-a3f2-b84cbb5274f3", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.25, para 5](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "908f6e06-2d57-400f-8688-599514f0491f", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.25, para 5](https://elifesciences.org/articles/95402)"}, "hash": "9f0c860bb9b51aa146bee6435c928e697e5c27304537f698cc7c203973fb6bf9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### MALE VENTRAL NERVE CORD", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 27, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "317e9045-9d0f-453c-bf80-471d0cf8d86c": {"__data__": {"id_": "317e9045-9d0f-453c-bf80-471d0cf8d86c", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.25, para 6](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3ee0f558-1a08-4d59-882b-be4104ab9d94", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.25, para 6](https://elifesciences.org/articles/95402)"}, "hash": "7d475e38b4c08d8b5be66c25945ae15199b333606690f3ab1927d1bf111072ee", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* **ventral view**\n  * unc-17^CRISPR ::gfp\n  * NeuroPAL\n  * MERGE\n* **CA1**\n* **CP1**\n* **CA2**\n* **CP2**\n* **CA3**\n* **CP3**", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 125, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6a8e0ffe-a5e7-4c66-8052-e621e27acfb1": {"__data__": {"id_": "6a8e0ffe-a5e7-4c66-8052-e621e27acfb1", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.25, para 7](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2e2e762f-0702-4fb1-9748-73183e38671f", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.25, para 7](https://elifesciences.org/articles/95402)"}, "hash": "8b6982f8c7455fd724de9584b17c8dac0456c1afa3958c8867c358e0f7af31b7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### MALE TAIL", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 13, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6e4e6b56-3336-4b04-97b8-5e62b8951192": {"__data__": {"id_": "6e4e6b56-3336-4b04-97b8-5e62b8951192", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.25, para 8](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "aa9ca049-c943-475c-b67c-e9db00b95eb1", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.25, para 8](https://elifesciences.org/articles/95402)"}, "hash": "5a54c880418505807bec44aacb4062155d0d55b37beb22e6d461a790cbe95b24", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* **ventral view**\n  * unc-17^CRISPR ::gfp\n  * NeuroPAL\n  * MERGE\n* **R1B**\n* **R4B**\n* **R5B**\n* **R7B**\n* **R9B**\n* **DX3/4**", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 127, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fba75277-b049-4b3a-bd40-d79a5cdcd958": {"__data__": {"id_": "fba75277-b049-4b3a-bd40-d79a5cdcd958", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.25, para 9](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1327e2b7-b5e4-4b34-822d-a4cd5c56fbfc", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.25, para 9](https://elifesciences.org/articles/95402)"}, "hash": "f56ef2c6c8f0f98718e0330df1ef153d0588ab7ecb528c24bbe9d49621d16962", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## C", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0b3fbf77-7d2a-4f68-a089-a4cefaa06f20": {"__data__": {"id_": "0b3fbf77-7d2a-4f68-a089-a4cefaa06f20", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.25, para 10](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "42b4f384-6d9a-4c9b-9996-ef8954810cfb", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.25, para 10](https://elifesciences.org/articles/95402)"}, "hash": "c0cb5826f989d15d504206dedd2b9ecc3f0f449c039d0da2251a007dbdddb6f0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|P2-derived|P3-derived|P4-derived|P5-derived|P6-derived|P7-derived|P8-derived|P9-derived|P10-derived|P11-derived||\n|-|-|-|-|-|-|-|-|-|-|-|\n|CA|CA1|CA2|CA3|CA4|CA5|CA6|CA7|CA8|CA9||\n||unc-17|unc-17|unc-17|unc-17|unc-17|unc-17|unc-17|unc-17|unc-17|unc-17|\n||unc-47|unc-47|unc-47|unc-47|unc-47|unc-47|eat-4|unc-47|||\n|CP|CP0|eat-4|eat-4|eat-4|eat-4|CP5|CP6|CP7|CP8|CP9|\n||CP1|CP2|CP3|CP4|||||||\n|eat-4|unc-17|unc-17|unc-17|unc-17|eat-4|eat-4|unc-17|unc-17|GABA(+)||\n||unc-47|unc-47|unc-47|unc-47|unc-47|unc-47|unc-47|unc-47|||\n||5-HT(+)|5-HT(+)|5-HT(+)|5-HT(+)|5-HT(+)|5-HT(+)|5-HT(+)|5-HT(+)|||", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 592, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "41182d35-17af-4d35-bb93-8b410f0854de": {"__data__": {"id_": "41182d35-17af-4d35-bb93-8b410f0854de", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.26, para 1](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9ff4541d-8059-4504-811d-c2c65950e566", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.26, para 1](https://elifesciences.org/articles/95402)"}, "hash": "7fe0049470540f44d8e7350eeb6bfa81cbe8c952f3a92c0c028da8ad571bab93", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Figure 10 continued\nvisible, albeit very dim, novel expression of eat-4 (also expressed in CA4). Bottom panels: CA7 strongly expresses eat-4(syb4257), whereas CP7 does not. Neuron IDs for these two neurons were previously switched (Serrano-Saiz et al., 2017b). (B) unc-17(syb4491) expression. Top, long panels: ventral view of a male ventral nerve cord showing high levels of expression in CA1, CA2, and CA3 and previously unreported low levels of expression in CP1, CP2, and CP3. Middle panels: low levels of expression in CA7 and CP7. There is no visible expression in CP9. Bottom panels: lateral view of a male tail showing previously unreported dim expression in R1B, R4B, R5B, R7B, and R9B; ventral view of the preanal ganglion showing expression in DX3/4. Scale bars, 10 \u00b5m. (C) The updated neurotransmitter atlas underscores the molecular diversity of the male-specific ventral cord neuron class CA and CP. Based on their expression patterns for neurotransmitter genes, these neurons can be grouped into four CA and five CP subclasses.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1042, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a669fd80-33d2-4aaf-ac27-b62e42b0ac85": {"__data__": {"id_": "a669fd80-33d2-4aaf-ac27-b62e42b0ac85", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.26, para 2](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cb10ac07-07e0-4887-9f19-c51cbd373fbb", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.26, para 2](https://elifesciences.org/articles/95402)"}, "hash": "56cf5438da5f04079eaa3e8bc43fff618398efc9e7f9957697c6d3595cd03396", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Serotonin/5-HT synthesis", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 27, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6feef166-5844-4c69-ab51-0cc4855dc680": {"__data__": {"id_": "6feef166-5844-4c69-ab51-0cc4855dc680", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.26, para 3](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "db9704a4-5dd8-454a-adf6-05bacf033809", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.26, para 3](https://elifesciences.org/articles/95402)"}, "hash": "8ff810c5e14a06993078f79d2080867920ed33fc0f8cbd9b54d14815bccc602c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Serotonergic identity had been assigned to several male-specific neurons before (CP1 to CP6, R1B, R3B, R9B) (Loer and Kenyon, 1993), and we validated these assignments with our reporter alleles (Figure 12, Supplementary file 3). In addition, we detected previously unreported expression of tph-1 (Figure 12B) in the male-specific head neuron class CEM, as well as in a subset of B-type ray sensory neurons, R4B and R7B. However, not all of the neurons display additional, canonical serotonergic neuron features: While R4B and R7B express bas-1(syb5923) (with R4B expressing it variably) to generate serotonin, neither neuron was detected by anti-serotonin staining in the past. On the other hand, R9B and CEM stain positive for 5-HT (Serrano-Saiz et al., 2017b), but they do not express bas-1(syb5923), indicating that they may be producing 5-HTP rather than 5-HT (serotonin)(see more below on serotonin uptake). In addition, R4B and R9B, but not R7B or CEM, express cat-1(syb6486) for vesicular release of serotonin.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1017, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e506cb69-fe10-4519-b43c-243f8602f9b1": {"__data__": {"id_": "e506cb69-fe10-4519-b43c-243f8602f9b1", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.26, para 4](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "82970e3d-1736-4394-8402-88403e958e67", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.26, para 4](https://elifesciences.org/articles/95402)"}, "hash": "981332160a553e5fc4eb7e537cba4a7de0b1d83048f2700c9e13e99008b17ea1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In the ventral nerve cord, consistent with previous fosmid-based reporter data (Serrano-Saiz et al., 2017b), we observed the expression of cat-1(syb6486) and tph-1(syb6451) in CP1 to CP6 (Supplementary file 3). Additionally, we also detected novel expression of bas-1(syb5923) in CP1 to CP4 and strongly in CP5 and CP6 (Figure 12C, Supplementary file 3). This updated expression supports the serotonergic identities of these neurons, which had been determined previously based only on their expression of cat-1/VMAT reporters and positive staining for serotonin (Loer and Kenyon, 1993; Serrano-Saiz et al., 2017b).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 614, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4aa8290e-17f7-4a1b-b320-ff3d199e877a": {"__data__": {"id_": "4aa8290e-17f7-4a1b-b320-ff3d199e877a", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.26, para 5](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "303f644e-ab87-431a-87b3-3952df6c9408", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.26, para 5](https://elifesciences.org/articles/95402)"}, "hash": "cde915f6e6b2cdd67216326d37797b3ea36c55b2e8360e8d36d83e7a3c157e09", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Dopamine synthesis", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 21, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c9673bb7-8070-444b-8c88-332536458cfc": {"__data__": {"id_": "c9673bb7-8070-444b-8c88-332536458cfc", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.26, para 6](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "973ed90d-a661-485e-8163-0712d6c882bb", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.26, para 6](https://elifesciences.org/articles/95402)"}, "hash": "866f7ed509e8c6e25569cbf844226e34b1e7e3a814492512bb3674f3def336bb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We found that the expression of the dopamine-synthesizing cat-2(syb8255) reporter allele precisely matched previous assignments of dopaminergic identity (Sulston et al., 1975; Sulston et al., 1980; Lints and Emmons, 1999), i.e., expression was detected exclusively in R5A, R7A, and R9A (Figure 13A, Supplementary file 3), in addition to all sex-shared dopaminergic neurons. All these neurons show matching expression of bas-1/AAAD, the other essential enzyme for dopamine synthesis, and cat-1/VMAT, the vesicular transporter for dopamine (Figure 12A and C; Supplementary file 3).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 579, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1d253962-5f12-4c4a-9dcf-6df3cc6005c9": {"__data__": {"id_": "1d253962-5f12-4c4a-9dcf-6df3cc6005c9", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.26, para 7](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "18c4d307-4be4-4f39-885b-e8487ffce792", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.26, para 7](https://elifesciences.org/articles/95402)"}, "hash": "a68ad8251652c2bd6180c233918e8325d7bb3cf42e549d4fc6fc0fd4b98422c5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Tyramine and octopamine synthesis", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 36, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "035fe562-591f-43b3-9e75-439812742b1d": {"__data__": {"id_": "035fe562-591f-43b3-9e75-439812742b1d", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.26, para 8](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "583673e0-19b0-41ce-8e59-19864262a184", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.26, para 8](https://elifesciences.org/articles/95402)"}, "hash": "17da9e885346154007018c19a01d57d049af8372443532341cbb72bda44d4f9c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Reporter alleles for the two diagnostic enzymes, tdc-1/TDC and tbh-1/TBH, confirm the previously reported assignment of HOA as tyraminergic (Serrano-Saiz et al., 2017b), based on the presence of tdc-1(syb7768) but absence of tbh-1(syb7786) expression (Figure 13 B and C). The tdc-1 reporter allele reveals a novel site of expression in R7A. Due to lack of tbh-1 expression, R7A therefore classifies as another tyraminergic neuron. Both HOA and R7A also co-express cat-1/VMAT for vesicular release of tyramine (Figure 12A).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 522, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8119ab02-4ad8-42bc-92bb-b3e49206deb8": {"__data__": {"id_": "8119ab02-4ad8-42bc-92bb-b3e49206deb8", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.26, para 9](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c4f2db19-6939-4f90-9343-871c89f765f4", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.26, para 9](https://elifesciences.org/articles/95402)"}, "hash": "1b0636a21dcd0bbc18cede013855366b5b2fbcea4f6a7ff2b1ceb67b8c552ed8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We detected no neurons in addition to the sex-shared RIC neuron class that shares all features of a functional octopaminergic neuron, i.e., co-expression of tbh-1/TBH, tdc-1/TDC, and cat-1/VMAT. While one male-specific neuron, R8B, shows an overlap of expression of tdc-1(syb7768) and tbh-1(syb7786) (Figure 13B and C), indicating that these neurons can synthesize octopamine, R8B does not express cat-1(syb6486), indicating that it cannot engage in vesicular release of octopamine.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 482, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a36bf19e-f2e2-4be2-afe7-69b83ae7713b": {"__data__": {"id_": "a36bf19e-f2e2-4be2-afe7-69b83ae7713b", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.26, para 10](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "62b65aaa-386a-46a8-a640-40a817051bc8", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.26, para 10](https://elifesciences.org/articles/95402)"}, "hash": "74cb8ed7694b7396b37b2dbd404f94b67f5ca6d2193e7704f52214ec38714996", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Curiously, while there are no other male-specific neurons that co-express tdc-1 and tbh-1, several male-specific neurons express tbh-1, but not tdc-1 (Figure 13B and C; Table 2, Supplementary file 3). The absence of the TDC-1/AAAD protein, which produces tyramine, the canonical substrate of the", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 295, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "aa693d63-8d6c-4d09-b6b2-d89757840b4a": {"__data__": {"id_": "aa693d63-8d6c-4d09-b6b2-d89757840b4a", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.27, para 0](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a80a8fa6-f8be-41a7-806d-fe26df1b1db7", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.27, para 0](https://elifesciences.org/articles/95402)"}, "hash": "5a0829af1e4afc25eb3491377df187c536afa06f579df9639111b383ada11e9e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Figure 11. Expression of GABAergic reporter alleles in the adult male. Neuronal expression of unc-25(ot1372) and unc-47(syb7566) reporter alleles was characterized with landmark strain NeuroPAL (otIs669). Only selected neurons are shown to illustrate updates from previous reports. See Supplementary file 3 for a complete list of neurons. (A) unc-25(ot1372) is expressed in male-specific CP9 and EF neurons as well as a few sex-shared neurons, all consistent with previous reports (Gendrel et al., 2016; Serrano-Saiz et al., 2017b). (B) unc-47(syb7566) shows expression in male head", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 584, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a91fd095-67c9-48b8-9160-14f6378439ee": {"__data__": {"id_": "a91fd095-67c9-48b8-9160-14f6378439ee", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.27, para 1](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cf10b501-f425-45b2-9ecd-650a9ed2a1ab", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.27, para 1](https://elifesciences.org/articles/95402)"}, "hash": "484de35e973c2e96fb5ec72f222ebb7f163e0ae939ed816ad1678e62544d7eef", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## A", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ed3d69da-bb37-47c2-b436-214c0bd915e9": {"__data__": {"id_": "ed3d69da-bb37-47c2-b436-214c0bd915e9", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.27, para 2](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8bb89fc7-3b2a-44b7-9144-e9c345faeeec", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.27, para 2](https://elifesciences.org/articles/95402)"}, "hash": "271b7638c769b963616d074cc700bbce1d5d76b8c7349a164b6c90c69a08c033", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### unc-25(ot1372\\[unc-25::t2a::gfp::h2b]) III", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 46, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7a703301-dede-4165-81a2-3eaee72e118d": {"__data__": {"id_": "7a703301-dede-4165-81a2-3eaee72e118d", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.27, para 3](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "299a6efc-8c92-40f7-befb-05d031d52016", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.27, para 3](https://elifesciences.org/articles/95402)"}, "hash": "b4fd1a4a8aa6ace15ce7611d134b57cf61ccb825adbc194601ea0ba174a17427", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "#### MALE TAIL", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 14, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8eb67ab0-ae84-4008-81cb-ed0ca64f9fa2": {"__data__": {"id_": "8eb67ab0-ae84-4008-81cb-ed0ca64f9fa2", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.27, para 4](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b7c1066e-41d4-4692-9313-fd4dc0867754", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.27, para 4](https://elifesciences.org/articles/95402)"}, "hash": "41f3cf68492b40d7a01dde4646872d76e50c455dd8b31cada530e83c532f53b6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* lateral view\n* **unc-25^CRISPR::gfp**\n  * EF1/2\n  * EF1/2\n  * EF3/4\n  * VD13\n  * VD12\n  * DD6\n  * CP9\n  * VD11\n* **NeuroPAL**\n  * EF1/2\n  * EF1/2\n  * EF3/4\n  * VD13\n  * VD12\n  * DD6\n  * CP9\n  * VD11\n* **MERGE**\n  * EF1/2\n  * EF1/2\n  * EF3/4\n  * VD13\n  * VD12\n  * DD6\n  * CP9\n  * VD11", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 285, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a031ae09-8973-43c2-a458-c9290c8272de": {"__data__": {"id_": "a031ae09-8973-43c2-a458-c9290c8272de", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.27, para 5](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "abcbaa0f-4fc8-4de7-add1-f50a7100c0a0", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.27, para 5](https://elifesciences.org/articles/95402)"}, "hash": "b2dde8228e3a5cfe3f2677bc1e28f627514793393700bc84ba2c251a3ecfc81f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## B", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "79982f47-a887-445d-ab1a-ea22a90fd434": {"__data__": {"id_": "79982f47-a887-445d-ab1a-ea22a90fd434", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.27, para 6](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f4e785a3-d7c6-48e2-895c-43d336334f41", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.27, para 6](https://elifesciences.org/articles/95402)"}, "hash": "abca5f97d01255bc4917c18f852afc7c0a34b04ece17884eb1fdb06e5c118d2d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### unc-47(syb7566\\[unc-47::sl2::gfp::h2b]) III", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 47, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8748a337-5fcd-462d-8c92-9a940479d9ed": {"__data__": {"id_": "8748a337-5fcd-462d-8c92-9a940479d9ed", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.27, para 7](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d58ba021-a15f-4a49-85e6-d895daa2069e", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.27, para 7](https://elifesciences.org/articles/95402)"}, "hash": "dbbc771d2ac81eb8adceb7044882d58a2e7ce7b3d951c492f9ef812347d78d2c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "#### MALE HEAD", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 14, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fae4817c-e8fa-4b2d-8a5d-e6668436f51f": {"__data__": {"id_": "fae4817c-e8fa-4b2d-8a5d-e6668436f51f", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.27, para 8](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "802ce228-6251-493f-a0b9-32dd77530670", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.27, para 8](https://elifesciences.org/articles/95402)"}, "hash": "cca3490c1883a7a0045618d1fb5cd8683beba54a67fb75c2c1a1546ab7f16912", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* **unc-47^CRISPR::gfp**\n  * MCM\n* **NeuroPAL**\n  * MCM\n  * AMso (landmark)\n* **MERGE**\n  * MCM\n  * AMso (landmark)\n* **unc-47^CRISPR::gfp**\n  * CEMD\n  * CEMV\n* **NeuroPAL**\n  * CEMD\n  * CEMV\n* **MERGE**\n  * CEMD\n  * CEMV", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 221, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6a130455-b6ae-449c-837b-43853ec83f11": {"__data__": {"id_": "6a130455-b6ae-449c-837b-43853ec83f11", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.27, para 9](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1b26786c-1b2c-44dd-9f4b-c04a7aceb02f", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.27, para 9](https://elifesciences.org/articles/95402)"}, "hash": "01e16b46d50dcc19f356edc1451d0ce2d2f2ecb47ddd3d2f6f74c24fead261e1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## C", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1b4c8eb1-c759-430b-b7c1-530c06ea67f6": {"__data__": {"id_": "1b4c8eb1-c759-430b-b7c1-530c06ea67f6", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.27, para 10](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f733b511-47c9-4dd4-8709-6a5f43f17f49", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.27, para 10](https://elifesciences.org/articles/95402)"}, "hash": "2cb52d7340221ad4321a43746f2093038a096ce87c28a0e5046f90eda000dd78", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### MALE VENTRAL NERVE CORD (ventral view)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 42, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fbf0be83-3ccc-4e15-a313-22612dfaa7de": {"__data__": {"id_": "fbf0be83-3ccc-4e15-a313-22612dfaa7de", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.27, para 11](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "716d1bcf-43e0-44ca-8b67-05964374fe27", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.27, para 11](https://elifesciences.org/articles/95402)"}, "hash": "e2861665e5bac34c4749ff146df581ace57afef3c4de5eb67e8f1a2ee302966c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* **unc-47^CRISPR::gfp**\n  * CA1\n  * CP1\n  * CA2\n  * CP2\n  * CA3\n  * CP3\n  * CA4\n  * CP4\n  * CA5\n  * CP5\n  * CA6\n  * CP6\n  * CA7(-)\n  * CP7\n  * CA8\n  * CP8\n  * CA9(-)\n  * CP9\n  * R2A\n  * R9B\n* **Neuro PAL**\n  * CA1\n  * CP1\n  * CA2\n  * CP2\n  * CA3\n  * CP3\n  * CA4\n  * CP4\n  * CA5\n  * CP5\n  * CA6\n  * CP6\n  * CA7\n  * CP7\n  * CA8\n  * CP8\n  * CA9\n  * CP9\n  * R2A\n  * R9B\n* **MERGE**\n  * CA1\n  * CP1\n  * CA2\n  * CP2\n  * CA3\n  * CP3\n  * CA4\n  * CP4\n  * CA5\n  * CP5\n  * CA6\n  * CP6\n  * CA7\n  * CP7\n  * CA8\n  * CP8\n  * CA9\n  * CP9\n  * R2A\n  * R9B", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 538, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8afd55bb-0684-4605-b8ff-dd441a1f56b4": {"__data__": {"id_": "8afd55bb-0684-4605-b8ff-dd441a1f56b4", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.28, para 0](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "619db42b-825e-4385-9d28-9677b87e76c0", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.28, para 0](https://elifesciences.org/articles/95402)"}, "hash": "e60da50b7333069a431dfa6a5c4279af1a2c6fcec30852602a52ed638485464d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# eLife Tools and resources", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 27, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4b606545-4345-4b2c-85cd-ef3672418b90": {"__data__": {"id_": "4b606545-4345-4b2c-85cd-ef3672418b90", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.28, para 3](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ca84e506-5a16-485f-b49e-30f1cbe57e58", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.28, para 3](https://elifesciences.org/articles/95402)"}, "hash": "fe8f03b4c4f54f077bb1a586748f3fc5be8b8f75c2b8dd61fc039148352469ea", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "neuron classes MCM and CEM, the former previously undetected and the latter consistent with fosmid-based reporter *otIs564*. (C) *unc-47(syb7566)* shows expression in a number of ventral cord CA and CP neurons, largely consistent with reported *otIs564* fosmid-based reporter expression except for no visible expression of *syb7566* in CA7 (due to its initial confusion with CP7, described in Figure 10) and presence of very dim expression in CP7. The *syb7566* reporter allele is also not visible in CA9. Scale bars, 10 \u00b5m.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 524, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e386226c-6fe4-4df7-b89f-e95e91df4441": {"__data__": {"id_": "e386226c-6fe4-4df7-b89f-e95e91df4441", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.28, para 4](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a61cefe5-a326-482b-bc8f-4e2fa993345f", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.28, para 4](https://elifesciences.org/articles/95402)"}, "hash": "b8861bd3c2dc4fb56802628afe20ec67f3029068c89f5b8511e5379b1ebfd94c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "TBH-1 enzyme (Figure 1A), indicates that TBH-1 must be involved in the synthesis of a compound other than octopamine. Moreover, *bas-1/AAAD* is expressed in several of the *tbh-1(+); tdc-1(-)* neurons (R1B, R2B, R3B, R4B, and R7B) (Figure 12C, Table 2, Supplementary file 3). Rather than using L-Dopa or 5-HTP as substrate, BAS-1/AAAD may decarboxylate other aromatic amino acids, which then may serve as a substrate for TBH-1. We consider the trace amine phenylethanolamine (PEOH) as a candidate end product (see Discussion).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 526, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "61d32c21-4340-4ea1-83cb-2b4c2615eab8": {"__data__": {"id_": "61d32c21-4340-4ea1-83cb-2b4c2615eab8", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.28, para 5](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "061ec507-e15a-468d-a5ae-d95a93f5c79c", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.28, para 5](https://elifesciences.org/articles/95402)"}, "hash": "023e0f758edd9771cd1f37b5b35c7d8348f29bcaa3b072477faf525b51e01b02", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Other monoaminergic neurons", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 30, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e54d7d47-5702-4ecc-8171-1c8bc7fafcaf": {"__data__": {"id_": "e54d7d47-5702-4ecc-8171-1c8bc7fafcaf", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.28, para 6](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "784c93f3-5db9-436f-bf74-2cf4e146f624", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.28, para 6](https://elifesciences.org/articles/95402)"}, "hash": "8c9aec5748a432646c1ae414baade9b57e14ed098cf767ddd6da4374d6021679", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In the preanal ganglion, we detected novel expression of the *cat-1(syb6486)* reporter allele in the cholinergic PDC, PVX, and PVY neurons (Figure 12A). Intriguingly, just as the sex-shared neuron AVL (Figure 6C), these neurons express no other serotonergic, dopaminergic, tyraminergic, or octopaminergic pathway genes. However, we did find PDC (but not PVX or PVY) to express the betaine uptake transporter reporter allele *snf-3(syb7290)* (Figure 9; more below). PVX and PVY may synthesize or uptake another aminergic transmitter. Such presumptive transmitter is not likely to be synthesized by *hdl-1/AAAD* since we detected no expression of the *hdl-1* reporter allele *syb4208* in the male nervous system.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 710, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6a2001b3-5bb8-4ba3-895a-c10ce539fcf4": {"__data__": {"id_": "6a2001b3-5bb8-4ba3-895a-c10ce539fcf4", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.28, para 7](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7cd9aadf-917f-4e62-b21c-bb05df1dbb47", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.28, para 7](https://elifesciences.org/articles/95402)"}, "hash": "a15930a43bd9284768f70ebecdaacad5d28926778318221ef06c0cd6f9882150", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The expression pattern of the *bas-1/AAAD*, which had not been previously analyzed in the male-specific nervous system, reveals additional novelties. In addition to the \u2018canonical\u2019 serotonergic and dopaminergic neurons described above, we detected *bas-1(syb5923)* reporter allele expression in a substantial number of additional neurons, including the tyraminergic HOA and R7A neurons, but also the DVE, DVF, R2A, R3A, R6A, R8A, R2B, R6B, R7B, PCB, and SPC neurons (Figure 12C, Supplementary file 3). As described above, a subset of the neurons co-express *tbh-1(syb7786)* (most B-type ray neurons), a few co-express *tdc-1(syb7768)* (HOA and several A-type ray neurons), and several co-express neither of these two genes. Only a subset of these neurons express *cat-1(syb6486)*. Taken together, this expression pattern analysis argues for the existence of additional monoaminergic signaling system(s) (Table 2).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 913, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "07fd90a6-a6d9-45ea-acdd-901812ba4f7b": {"__data__": {"id_": "07fd90a6-a6d9-45ea-acdd-901812ba4f7b", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.28, para 8](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "70475926-f0d0-47b3-a51a-08fe909faab8", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.28, para 8](https://elifesciences.org/articles/95402)"}, "hash": "f1986896eaa7e72ddb788e87fdd51cfca6d7b43825c1e8b604f93719967d7045", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Serotonin/5-HT uptake", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 24, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6b13b22d-e870-4530-b6bd-0a9a46703f2f": {"__data__": {"id_": "6b13b22d-e870-4530-b6bd-0a9a46703f2f", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.28, para 9](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "da29d62b-2407-46fc-871f-e84c244735c3", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.28, para 9](https://elifesciences.org/articles/95402)"}, "hash": "860248e4cf25a24dfd8ede946525da404ef17ef4e06e931b26fb17f8d649481c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In the male-specific nervous system, we detected *mod-5/SERT* reporter allele expression in CEM, PGA, R3B, R9B, and ventral cord neurons CP1 to CP6 (Figure 8D). We found that anti-serotonin staining in CP1 to CP6, R1B, and R3B is unaffected in *mod-5(n3314)* mutant animals, consistent with these neurons expressing the complete serotonin synthesis machinery (i.e. *tph-1* and *bas-1*) (Table 2, Figure 8B, D, and G; Supplementary file 3). Hence, like several other monoaminergic neurons, these serotonergic neurons both synthesize, synaptically release, and reuptake serotonin. In contrast, anti-serotonin staining is lost from the R9B and PGA neurons of *mod-5(n3314)* mutant animals, indicating that the presence of serotonin in these neurons depends on serotonin uptake, consistent with them not expressing the complete serotonin synthesis pathway (Table 2; Supplementary file 3). Since R9B and PGA express *cat-1/VMAT* (Figure 12A), these neurons have the option to utilize serotonin for vesicular release after *mod-5*-dependent uptake.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1042, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "44632a1b-b0b2-4c28-a182-4dd2204ba473": {"__data__": {"id_": "44632a1b-b0b2-4c28-a182-4dd2204ba473", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.28, para 10](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9e0bf2ef-6ff2-4ae7-9723-f8c4c6c5c0b1", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.28, para 10](https://elifesciences.org/articles/95402)"}, "hash": "f645ad5871972bfb74bef75a01dc6c7d5452a89d0ce0b40dac8bbf15136ec067", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Tyramine and betaine uptake", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 30, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ac12a621-7327-46f6-bf86-5e0455ce07a6": {"__data__": {"id_": "ac12a621-7327-46f6-bf86-5e0455ce07a6", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.28, para 11](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b88dc1ca-efeb-49ba-bcec-2fdc753f7bad", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.28, para 11](https://elifesciences.org/articles/95402)"}, "hash": "08fc53898e05cfc04a08e013a42252d899b8598ce0d25bbba7a01c5480acf0c6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We did not observe *oct-1(syb8870)* reporter allele expression in male-specific neurons. As in the hermaphrodite nervous system, we detected *snf-3(syb7290)* in a number of neurons that do not express CAT-1/VMAT (Supplementary file 1), including in male-specific neurons PHD, and variably, PVV (Figure 9C). As mentioned earlier, the male-specific neuron PDC expresses both *cat-1(syb6486)* and *snf-3(syb7290)*, making it a likely betaine-signaling neuron.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 456, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "51a2e514-408e-4c7a-8d8a-d656e036996d": {"__data__": {"id_": "51a2e514-408e-4c7a-8d8a-d656e036996d", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.29, para 0](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b9e9e8a6-559d-4f24-8779-d8a4bc4682d5", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.29, para 0](https://elifesciences.org/articles/95402)"}, "hash": "2d638efc222758b3fb627fff62b35b364b432e5c2bc560cc72cf8aa1e5d341f6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# eLife Tools and resources", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 27, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "db679fd5-cbf2-4151-9944-5a15b77728c8": {"__data__": {"id_": "db679fd5-cbf2-4151-9944-5a15b77728c8", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.29, para 2](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "719fbcb2-6508-4c84-8405-77b1e9dfa224", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.29, para 2](https://elifesciences.org/articles/95402)"}, "hash": "bc61e6f368284648bb77ddaaef649d864f96a43ecc8e8ec3bc9c7deccb905854", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Figure 12. Expression of the cat-1/VMAT, tph-1/TPH, and bas-1/AAAD reporter alleles in the adult male. Neuronal expression was characterized with landmark strain NeuroPAL (otIs669). (A) Novel cat-1(syb6486) expression is seen in male-specific neurons PDC, PVY, PVX, R2A, and R4B. Consistent with previous reports, it is also expressed in HOA, PGA, R5A, R7A, R9A, R1B, and R8B. Its expression in ventral cord neurons CP1 to CP6 is consistent with earlier studies. (B) tph-1(syb6451) is expressed in male-specific head neuron class CEM and sex-shared neurons ADF, NSM, and MI. Similar to its expression in hermaphrodites, tph-1 in MI was previously undetected. In the tail, in addition to previously determined expression in R1B, R3B, and R9B,", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 744, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "62c6c7f0-e3fe-45f2-aed2-ab9d534b6f35": {"__data__": {"id_": "62c6c7f0-e3fe-45f2-aed2-ab9d534b6f35", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.30, para 1](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9f28709f-de09-410f-a8a1-41b12f789a46", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.30, para 1](https://elifesciences.org/articles/95402)"}, "hash": "a9afdb03ddf517ab794f82ebb5c4bf73d4d4d0ab5e35f0b8fbc901defa8145ef", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Figure 12 continued\ntph-1(syb6451) is also expressed at very low levels in R4B and R7B. Ventral cord expression of tph-1(syb6451) in CP1 to CP6 is consistent with previous reports and thus not shown here. (C) bas-1(syb5923) is expressed in previously identified NSM, ADE, PDE, and CEP neurons. In addition, we detected weak expression in URB as in the hermaphrodite. We also updated bas-1/AAAD expression in 39 male-specific neurons (see Supplementary file 3 for complete list). Neurons are also shown in grayscale for clearer visualization in some cases. Scale bars, 10 \u00b5m. Asterisks, non-neuronal expression, also see Figure 14 and Figure 14\u2014figure supplement 1.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 664, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d4bf16bc-7637-48b0-9cf8-09e904d99f32": {"__data__": {"id_": "d4bf16bc-7637-48b0-9cf8-09e904d99f32", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.30, para 2](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f5d53259-72cc-4f2c-8fcc-898d65693811", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.30, para 2](https://elifesciences.org/articles/95402)"}, "hash": "6d1fd11cf210ee7087fac8976e76c5c26a05fcfe7b5b10f5267df01e682a2066", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Sexually dimorphic neurotransmitter deployment in sex-shared neurons", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 71, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "777786da-6359-4bb5-9928-8f151c1c1ef6": {"__data__": {"id_": "777786da-6359-4bb5-9928-8f151c1c1ef6", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.30, para 3](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "55cbbcad-884c-46fb-a893-515a419bf0e3", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.30, para 3](https://elifesciences.org/articles/95402)"}, "hash": "9e368685b1f05832c6a151a8771a4d41fba47cd1cf706e45142c9141358c94ce", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### eat-4/VGLUT", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 15, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "904c2309-92ce-41fd-b52a-afec1281b718": {"__data__": {"id_": "904c2309-92ce-41fd-b52a-afec1281b718", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.30, para 4](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "03f720db-c01d-4410-ab6f-2e59b07d6ec6", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.30, para 4](https://elifesciences.org/articles/95402)"}, "hash": "38aabc6109734db6e56c2e86a8cf67edf3ec9b9ac700693f233a64f247076bdf", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We had previously noted that a fosmid-based eat-4/VGLUT reporter is upregulated in the sex-shared neuron PVN, specifically in males (Serrano-Saiz et al., 2017b). Since PVN is also cholinergic (Figure 4D; Pereira et al., 2015), this observation indicates a sexually dimorphic co-transmission configuration. As described above (Figure 4B, Supplementary file 2), our eat-4 reporter allele revealed low levels of eat-4/VGLUT expression in hermaphrodites PVN, but in males the eat-4 reporter allele showed strongly increased expression, compared to hermaphrodites. Hence, rather than being an 'on' vs. 'off' dimorphism, dimorphic eat-4/VGLUT expression in male PVN resembles the 'scaling' phenomenon we had described previously for eat-4/VGLUT in male PHC neurons, compared to hermaphrodite PHC neurons (Serrano-Saiz et al., 2017a). Both PHC and PVN display a substantial increase in the amount of synaptic output of these neurons in males compared to hermaphrodites (Cook et al., 2019), providing a likely explanation for such scaling of gene expression. The scaling of eat-4/VGLUT expression in PVN is not accompanied by scaling of unc-17/VAChT expression, which remains comparable in both sexes (Figure 4D).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1205, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "50e5df2d-d59f-4486-aa93-7bebbb810c01": {"__data__": {"id_": "50e5df2d-d59f-4486-aa93-7bebbb810c01", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.30, para 5](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "eb8c92c2-c174-4022-a3a6-251febef6fd3", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.30, para 5](https://elifesciences.org/articles/95402)"}, "hash": "1569bc00dafbb5c816c1f2c1d925f448a04c9383d0e1690d3a3377de0e2c0eeb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We also examined AIM, another neuron class that was previously reported to be sexually dimorphic in that AIM expresses eat-4/VGLUT fosmid-based reporters in juvenile stages in both sexes, whereas upon sexual maturation its neurotransmitter identity is switched from being glutamatergic to cholinergic only in adult males and not hermaphrodites (Pereira et al., 2015; Pereira et al., 2019). With the eat-4(syb4257) reporter allele, we also detected a downregulation of eat-4 expression to low levels in young adult males and almost complete elimination in 2-day-old adult males, while expression in hermaphrodites stays high.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 624, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "dcc93f4a-8547-4176-bf55-9cf4877a1261": {"__data__": {"id_": "dcc93f4a-8547-4176-bf55-9cf4877a1261", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.30, para 6](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2dcba4d2-04fc-4623-9116-389f796370b0", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.30, para 6](https://elifesciences.org/articles/95402)"}, "hash": "36aeec8f1b6a13f2e2846791f8b793e4603b1562d6909cc84b9712666d41a634", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### unc-17/VAChT", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 16, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "852b8880-582f-463f-8de1-b88b3559d791": {"__data__": {"id_": "852b8880-582f-463f-8de1-b88b3559d791", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.30, para 7](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a3ab71bf-2dfd-416a-ade6-3206f81de67d", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.30, para 7](https://elifesciences.org/articles/95402)"}, "hash": "cb41b3725193dcaabe8637a139081ee47d3d035944cafa76dd25740b4103e1a2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The unc-17/VAChT reporter allele syb4491 confirms that cholinergic identity is indeed male-specifically turned on in the AIM neurons (Figure 4C), thereby confirming the previously reported neurotransmitter switch (Pereira et al., 2015). The fosmid-based unc-17 reporter also showed sexually dimorphic expression in the AVG neurons (Serrano-Saiz et al., 2017b). This is also confirmed with the unc-17 reporter allele, which shows dim and variable expression in hermaphrodites and slightly stronger, albeit still dim, AVG expression in males (Figure 4C, showing a hermaphrodite representing animals with no visible expression and a male with representative dim expression).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 671, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "67e43242-8885-4a20-adc4-0edff497256b": {"__data__": {"id_": "67e43242-8885-4a20-adc4-0edff497256b", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.30, para 8](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d91f51eb-ea53-45a2-8393-2c0d836ac1f6", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.30, para 8](https://elifesciences.org/articles/95402)"}, "hash": "6e50d82c181a001fa3320575ae257db2aa8b42afbe9e5f0dcda4552ed72976ce", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### unc-47/VGAT", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 15, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0dfbd7bf-e77c-42cc-bede-ed9b6ea3150a": {"__data__": {"id_": "0dfbd7bf-e77c-42cc-bede-ed9b6ea3150a", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.30, para 9](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b7e3d901-57b1-444f-87ed-1d5122a1e80d", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.30, para 9](https://elifesciences.org/articles/95402)"}, "hash": "e74c0df0507e655e806bfae2ac03f61764ec4261042f0761c4820542fd7bf225", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "unc-47(syb7566) confirms previously reported sexually dimorphic expression of unc-47/VGAT in several sex-shared neurons, including ADF, PDB, PVN, PHC, AS10, and AS11 (Figure 5B, right side panels) (Serrano-Saiz et al., 2017b). The assignment of AS10 was not definitive in our last report (we had considered either DA7 or AS10), but with the help of NeuroPAL the AS10 assignment could be clarified. In all these cases expression was only detected in males and not hermaphrodites. It is worth mentioning that expression of the mCherry-based unc-47/VGAT fosmid-based reporter (otIs564) in some of these neurons was so dim that it could only be detected through immunostaining against the mCherry fluorophore and not readily visible with the fosmid-based reporter by itself (Serrano-Saiz et al., 2017b; Supplementary file 1). In contrast, the unc-47/VGAT reporter allele is detected in all cases except the PQR neuron class.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 920, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "dcf3cb56-66c9-46ec-b7a1-b652fc5652cf": {"__data__": {"id_": "dcf3cb56-66c9-46ec-b7a1-b652fc5652cf", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.30, para 10](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fc5e3111-f8de-4a9c-81f8-8acbe6301844", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.30, para 10](https://elifesciences.org/articles/95402)"}, "hash": "384b54d1e489062c68c68e9af25c0553ebfa7cee59f551b8aeb3c644c3a48847", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### mod-5/SERT", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 14, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b9e49b87-7e7c-43fe-b03e-550eae409d66": {"__data__": {"id_": "b9e49b87-7e7c-43fe-b03e-550eae409d66", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.30, para 11](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "70657a68-2ff2-457b-9c88-ebea276f9ac0", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.30, para 11](https://elifesciences.org/articles/95402)"}, "hash": "e30953d2f613c1720fe0dbb7a8775bd5cae35dd337414d6ecc26134a7476b7b0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Expression of the mod-5(vlc47) reporter allele is sexually dimorphic in the pheromone-sensing ADF neurons, with higher levels in hermaphrodites compared to males (Figure 8F). Notably, the", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 187, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cd745c50-bc97-43f9-a0d9-c65643a568ed": {"__data__": {"id_": "cd745c50-bc97-43f9-a0d9-c65643a568ed", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.31, para 1](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3ab4e827-5e0f-4f6a-b744-566de7f71ec1", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.31, para 1](https://elifesciences.org/articles/95402)"}, "hash": "4a0c50319c14f0e5134574bb80ea8af80f657e3ee95805de8cadfc6945810fb7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# A", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 3, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "896bb9d9-3cee-4fb2-a117-f91665d3ad8c": {"__data__": {"id_": "896bb9d9-3cee-4fb2-a117-f91665d3ad8c", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.31, para 3](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "52076248-12ff-4e26-98bc-0edb59a46bc1", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.31, para 3](https://elifesciences.org/articles/95402)"}, "hash": "2c5c092c57d60a10e99e05ff46de5d6d3e35786413a55482dd9b464249d6a522", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## MALE TAIL", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 12, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5dcef942-c365-4dd2-adef-480d0a5a2c47": {"__data__": {"id_": "5dcef942-c365-4dd2-adef-480d0a5a2c47", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.31, para 8](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c561cf56-3511-41c0-b385-2d61ca57ba17", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.31, para 8](https://elifesciences.org/articles/95402)"}, "hash": "f30c6f23ce228f26610452bc4faf0b5364040640648ec32058146e5f3158bb74", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# B", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 3, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "49d2555f-6ddc-415c-b2e4-a0e31b281121": {"__data__": {"id_": "49d2555f-6ddc-415c-b2e4-a0e31b281121", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.31, para 10](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "af6ac68d-2a5a-4622-9aa0-5d6effee5aad", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.31, para 10](https://elifesciences.org/articles/95402)"}, "hash": "3322bc2bcd4f431f58dbdbe8032131da871a3a67cbc4157a742c9feb9c3aaea0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## MALE HEAD", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 12, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "405f1fb2-694a-4cce-8d55-c205c4a170d8": {"__data__": {"id_": "405f1fb2-694a-4cce-8d55-c205c4a170d8", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.31, para 12](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "92cba609-9393-4e9b-8663-f54a5245f83e", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.31, para 12](https://elifesciences.org/articles/95402)"}, "hash": "0c82f93a4b3e4521314312549e01fc15da234ed2c5eac664fe63fa2078b001fa", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## MALE TAIL", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 12, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "90b45b8f-65a5-4993-b2cd-81f72252377c": {"__data__": {"id_": "90b45b8f-65a5-4993-b2cd-81f72252377c", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.31, para 23](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "13006015-ef1a-40c4-bf5a-cc4416974995", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.31, para 23](https://elifesciences.org/articles/95402)"}, "hash": "6b877ad3594f2ce62cce3639867d1aca1b169fe96c24a04ee81e49faa896c323", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# C", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 3, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "aedceb22-23ff-4793-9548-9e66fd7bf217": {"__data__": {"id_": "aedceb22-23ff-4793-9548-9e66fd7bf217", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.31, para 25](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "66eb752b-7e28-4e25-a989-2a8db4e49737", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.31, para 25](https://elifesciences.org/articles/95402)"}, "hash": "8a12c61e33d34c96ce4e14e111efe7c5e833bb70edfcaae30172399ce5e65e16", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## MALE HEAD", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 12, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "320e2f21-f352-45b9-ad39-5c901776cdee": {"__data__": {"id_": "320e2f21-f352-45b9-ad39-5c901776cdee", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.31, para 27](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ad902e07-b80d-44de-8084-5816fa1d5ab2", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.31, para 27](https://elifesciences.org/articles/95402)"}, "hash": "f5558f4dcf61cb6fa86df58c5d35cb4fe545b6ab32e69f7bf6cb0001ba6596ef", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## MALE TAIL", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 12, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f1b79224-713c-4fe0-875c-1bcbf948e3e2": {"__data__": {"id_": "f1b79224-713c-4fe0-875c-1bcbf948e3e2", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.31, para 37](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d874ead8-71a6-443f-9b49-b53a3962a17a", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.31, para 37](https://elifesciences.org/articles/95402)"}, "hash": "0f70394b8a2cb68800838cdfe96a513b98cd1798a02324861f5e48afd3ccdc6c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Figure 13. Expression of cat-2/TH, tdc-1/TDC, and tbh-1/TBH reporter alleles in the adult male. Neuronal expression was characterized with landmark strain NeuroPAL (otIs669). (A) cat-2(syb8255) is expressed in male-specific neurons R4A, R7A, and R9B. This expression, as well as its expression in sex-shared neurons PDE, CEP, and ADE, is consistent with previous reports (Sulston et al., 1975; Sulston et al., 1980; Lints and Emmons, 1999). (B) tdc-1(syb7768) is expressed in sex-shared neurons RIM and RIC and male-specific neurons HOA, R8A, and R8B, all consistent with previous studies (Serrano-Saiz et al., 2017b). We also detected weak expression in R7A. (C) tbh-1(syb7786) is expressed in RIC, consistent with its previously reported expression in hermaphrodites. As in hermaphrodites, we also detected tbh-1(syb7786) in IL2 neurons of the male. In male-specific neurons, previously unreported expression is detected in CEM, HOB, and all type B ray neurons except for R6B. Intriguingly, this expression pattern resembles that of pkd-2 and lov-1, both genes essential for male mating functions (Barr and Sternberg, 1999; Barr et al., 2001). Inset, grayscale image showing dim expression for IL2 neurons. Scale bars, 10 \u00b5m. Asterisks, non-neuronal expression, also see Figure 14 and Figure 14\u2014figure supplement 1.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1317, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "69f6bc78-76b2-4e58-af3d-7c1f4abeacb2": {"__data__": {"id_": "69f6bc78-76b2-4e58-af3d-7c1f4abeacb2", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.32, para 1](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e955ff18-9630-4811-9c71-0020250b1e38", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.32, para 1](https://elifesciences.org/articles/95402)"}, "hash": "92230903007c0849781a6c59ccec33341ffa2518876e7ad0df191729549d1135", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "serotonin-synthesizing enzyme (*tph-1*) and vesicular acetylcholine transporter (*unc-17*) do not exhibit this dimorphism in ADF (Figure 8F). This suggests that the sex difference specifically involves serotonin signaling mechanisms, particularly serotonin uptake rather than synthesis.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 286, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d37b1886-974d-41d7-941e-131dce9420af": {"__data__": {"id_": "d37b1886-974d-41d7-941e-131dce9420af", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.32, para 2](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7ba739d4-7cf9-44ba-86ed-6d2d620fb459", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.32, para 2](https://elifesciences.org/articles/95402)"}, "hash": "90b05b4a40ae3b13afc3be5e40e528b0353611f5106f88457dcac5d56c4f30f1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We had previously reported that the PVW neuron stains with anti-serotonin antibodies exclusively in males but we did not detect expression of a fosmid-based reporter for the serotonin-synthesizing enzyme TPH-1 (Serrano-Saiz et al., 2017b). We confirmed the lack of *tph-1* expression with our new *tph-1* reporter allele in both males and hermaphrodites, and also found that hermaphrodite and male PVW does not express the reporter allele for the other enzyme in the serotonin synthesis pathway, *bas-1*. Because of very dim *cat-1::mCherry* fosmid-based reporter expression that was only detected upon anti-mCherry antibody staining, we had assigned PVW as a serotonin-releasing neuron (Serrano-Saiz et al., 2017b). However, we failed to detect expression of our new *cat-1/VMAT* reporter allele in PVW. Neither did we detect expression of the *mod-5(vlc47)* reporter allele. Taken together, PVW either synthesizes or uptakes serotonin by unconventional means, akin to the pharyngeal I5 neuron.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 995, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9b7a9fa3-fd3e-42d0-b4cb-b1c1b5df21f6": {"__data__": {"id_": "9b7a9fa3-fd3e-42d0-b4cb-b1c1b5df21f6", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.32, para 3](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ada20163-da58-4009-b8ad-7cc66ec5074e", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.32, para 3](https://elifesciences.org/articles/95402)"}, "hash": "be0437d286b2220920b78012d6434c529baf56ecfedbfdafc91d89d5afbfda96", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In conclusion, although there are some updates in the levels of dimorphic gene expression (PVN and ADF neuron classes), our analysis with reporter alleles does not reveal pervasive novel sexual dimorphism in sex-shared neurons compared to those that we previously identified in Serrano-Saiz et al., 2017b. These sexual dimorphisms are summarized in Supplementary file 4.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 370, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9895c36b-3958-4e37-80da-73ca2639e847": {"__data__": {"id_": "9895c36b-3958-4e37-80da-73ca2639e847", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.32, para 4](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "de012592-97a9-417e-ad25-a7cf1bb100f9", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.32, para 4](https://elifesciences.org/articles/95402)"}, "hash": "cc931250126dda2dab22fa7ce6d2a9eb3faae6bd12bc1713a99213dea2bcef51", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Neurotransmitter pathway genes in glia", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 41, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "926a5d33-8f64-4702-9eb6-e9dec4ccd9f6": {"__data__": {"id_": "926a5d33-8f64-4702-9eb6-e9dec4ccd9f6", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.32, para 5](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9f6b1d2d-88e6-4818-9c20-c93ad6af8fb5", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.32, para 5](https://elifesciences.org/articles/95402)"}, "hash": "bafa07e97aaaa725509bf1b78f47b90c7cc828b5daa82f0175dfbf378f205a81", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In vertebrates, glia can produce various signaling molecules, including neurotransmitters (Araque et al., 2014; Savtchouk and Volterra, 2018). There is some limited evidence for neurotransmitter synthesis in *C. elegans* glia. In males, it had been reported that the socket glia of spicule neurons synthesize and utilize dopamine, based on their expression of *cat-2/TH* and *bas-1/AAAD* (Lints and Emmons, 1999; Hare and Loer, 2004; LeBoeuf et al., 2014). We confirmed this notion with *cat-2/TH* and *bas-1/AAAD* reporter alleles (Figure 14A). Additionally, we detected expression of the *cat-1/VMAT* reporter allele in these cells (Figure 14A), indicating that these glia secrete dopamine by canonical vesicular transport. We did not detect *cat-1/VMAT* in other glial cell types. In addition to the spicule socket glia, we also observed *bas-1(syb5923)* reporter allele expression in cells that are likely to be the spicule sheath glia (Figure 14A), as well as in additional glial cell types in the head and tail (Figure 14B). We detected no glial expression of other monoaminergic synthesis machinery.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1106, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3b7b20d1-3841-44fb-87a4-044eea592427": {"__data__": {"id_": "3b7b20d1-3841-44fb-87a4-044eea592427", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.32, para 6](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "55d3e134-7288-4a12-94cf-c1dc456eda3c", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.32, para 6](https://elifesciences.org/articles/95402)"}, "hash": "cdb015834d530d24b54c3bc3c5ebcb8c8ac41ba9623dff789117af4ded14e117", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We detected no expression of vesicular transporters or biosynthetic synthesis machinery for non-aminergic transmitters in glia of either sex. This observation contrasts previous reports on GABA synthesis and release from the AMsh glial cell type (Duan et al., 2020; Fernandez-Abascal et al., 2022). We were not able to detect signals in AMsh with anti-GABA staining, nor with an SL2- or T2A-based GFP-based reporter allele for any *unc-25* isoform (Gendrel et al., 2016) (M Gendrel, pers. comm.; this paper).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 508, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "64d4f601-520e-4fb0-bd66-6075ea145cd2": {"__data__": {"id_": "64d4f601-520e-4fb0-bd66-6075ea145cd2", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.32, para 7](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4f891080-e610-45a3-887a-6f2986a5e9bf", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.32, para 7](https://elifesciences.org/articles/95402)"}, "hash": "5fd5cf451297d1f8ecafec2ea764fca93c44bffd4dcef0c5527f5db2e356ce5d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "There is, however, abundant evidence for neurotransmitter uptake by *C. elegans* glial cells, mirroring this specific function of vertebrate glia (Henn and Hamberger, 1971). We had previously shown that one specific glia-like cell type in *C. elegans*, the GLR glia, take up GABA via the GABA uptake transporter SNF-11 (Gendrel et al., 2016). We did not detect *unc-47/VGAT* fosmid-based reporter expression in the GLRs (Gendrel et al., 2016) and also detected no expression with our *unc-47/VGAT* reporter allele. Hence, these glia are unlikely to release GABA via classic vesicular machinery. Other release mechanisms for GABA can of course not be excluded. Aside from the *snf-11* expression in GLR glia (Gendrel et al., 2016), we detected expression of the putative tyramine uptake transporter *oct-1/OCT* in a number of head glial cells (Figure 8K), as well as broad glial expression of the betaine uptake transporter *snf-3/BGT1* in the head, midbody, and tail (Figure 9E and F). These results indicate tyramine and betaine clearance roles for glia.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1055, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5a6504bf-2d30-4beb-9518-4e2752f51030": {"__data__": {"id_": "5a6504bf-2d30-4beb-9518-4e2752f51030", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.32, para 8](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0aae29b9-c9c1-4d57-b12d-bcedc9049d9a", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.32, para 8](https://elifesciences.org/articles/95402)"}, "hash": "21dd81297808c065b90a1978828b8500364d01ce8ef01c4d09f05ef80e3ff0db", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Neurotransmitter pathway gene expression outside the nervous system", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 70, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fe472666-a66d-40ad-898d-69cd937abe31": {"__data__": {"id_": "fe472666-a66d-40ad-898d-69cd937abe31", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.32, para 9](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "dc25167f-2eaf-4d7a-bc37-fc581383bd85", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.32, para 9](https://elifesciences.org/articles/95402)"}, "hash": "630e10a73f1e79c9e54cb83af306d819ae424fa16317791bf0166192e7b3c987", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We detected expression of a few neurotransmitter pathway genes in cells outside the nervous system. The most prominent sites of reporter allele expression are located within the gonad. We detected expression of *tdc-1(syb7768)* and *tbh-1(syb7786)* reporter alleles in the gonad of hermaphrodite as well as *tdc-1(syb7768)* expression in the neuroendocrine uv1 cells (Figure 14C; Figure 14\u2014figure supplement 1), as previously reported (Alkema et al., 2005). Intriguingly, while *cat-1(syb6486)*", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 494, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "346d1b88-e300-4062-89c3-4e61271ff276": {"__data__": {"id_": "346d1b88-e300-4062-89c3-4e61271ff276", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.33, para 0](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "af512b7f-9c89-486d-8ab1-0f6ac6c9bd42", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.33, para 0](https://elifesciences.org/articles/95402)"}, "hash": "5150d3ecdd2ae7bdf72152143ba5e5a7d100888e7bb0fe8d972a4d26271403fd", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# eLife Tools and resources", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 27, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0d4c85ae-8d57-4ad9-95f1-91eb1df911ab": {"__data__": {"id_": "0d4c85ae-8d57-4ad9-95f1-91eb1df911ab", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.33, para 2](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e4561364-7d7b-4651-89fb-9910d54bdf22", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.33, para 2](https://elifesciences.org/articles/95402)"}, "hash": "c7d106c38a0b37788266c7278b5e1ff48beeabb26d85dbd596f4a2c27093d2c1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Figure 14. Expression of neurotransmitter pathway genes in non-neuronal cell types. Multiple neurotransmitter pathway genes show expression in glial cells (A, B) and other non-neuronal cell types (C\u2013E). Also see Figure 14\u2014figure supplement 1 for whole-worm views that capture more non-neuronal expression. (A) bas-1(syb5923), cat-2(syb8255), and cat-1(syb6486) reporter alleles exhibit expression in the male spicule glial cell types, largely consistent with previous reports (Lints and Emmons, 1999; Hare and Loer, 2004; LeBoeuf et al., 2014). (B) Top 6 panels: bas-1(syb5923) is expressed in additional, multiple glial cell types in the male tail. Left 3 panels: bas-1(syb5923) crossed into a pan-glial reporter otIs870\\[mir-228p::3xnls::TagRFP], confirming its expression in glial cells; right 3 panels: bas-1(syb5923) shows no overlap with the pan-neuronal marker component in NeuroPAL (otIs669). Bottom 2 panels: bas-1(syb5923) also shows expression in at least two glial cells in the head. A hermaphrodite head is shown here. Expression is similar in the male. (C) In the hermaphrodite vulval region, tdc-1(syb7768) is expressed in uv1, consistent with previous reports (Alkema et al., 2005). This expression in uv1 is not observed for either cat-1(syb6486) or oct-1(syb8870). An ida-1p::mCherry integrant vsls269\\[ida-1::mCherry] was used for identifying uv1. (D) Detection of eat-4(syb4257) expression in muscle cells in both sexes, most prominently in the head. (E) cat-1(syb6486), tdc-1(syb7768), and tbh-1(syb7786) are expressed in the male somatic gonad. All three have expression in the vas deferens; additionally, cat-1 and tbh-1 are also expressed in the seminal vesicle.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1686, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7a144c08-c941-40ea-99d1-6b2d996473ac": {"__data__": {"id_": "7a144c08-c941-40ea-99d1-6b2d996473ac", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.33, para 3](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0d00d47a-2e23-4950-8534-22d7797e5686", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.33, para 3](https://elifesciences.org/articles/95402)"}, "hash": "fc267fab41978b14f8ef2b2a2db7fb2ae5986268a317ed6a43a673e4104ba9d7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The online version of this article includes the following figure supplement(s) for figure 14:", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 93, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fff60799-0eb2-402e-b0d5-edb2282fa147": {"__data__": {"id_": "fff60799-0eb2-402e-b0d5-edb2282fa147", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.33, para 4](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ef800e11-dbb8-404c-b999-87e11698972e", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.33, para 4](https://elifesciences.org/articles/95402)"}, "hash": "6459b3ef3c6882731afb856499b4eca71534f179e5c17c3ad5198cf79680c395", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Figure supplement 1. Whole-worm images showing monoaminergic pathway gene expression in different tissue types.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 111, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "880dd484-2f31-42b8-be34-277191c2e66d": {"__data__": {"id_": "880dd484-2f31-42b8-be34-277191c2e66d", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.34, para 1](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c819bd3f-efcd-40da-ad5b-bb05ae11d0a7", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.34, para 1](https://elifesciences.org/articles/95402)"}, "hash": "2653229591b6f3aa77ea5a761fcb68e1777577c6114fe90c32fef4177e700231", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "is expressed in a midbody gonadal cell posterior to the vulva, likely the distal valve (Figure 6C, Figure 14\u2014figure supplement 1), we observed no expression of cat-1(syb6486) in the gonad or the uv1 cells (Figure 14C). This suggests alternative release mechanisms for tyramine and octopamine. A vertebrate homolog of the putative tyramine uptake transporter, oct-1, has been found to be located presynaptically and to co-purify with synaptosomes (Berry et al., 2016; Matsui et al., 2016), therefore indicating that this transporter may have the potential to also act in tyramine release, at least in vertebrate cells. However, we observed no expression of our oct-1 reporter allele in uv1 or gonadal cells.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 706, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "631d2ae5-79a4-40cd-8d5d-21b7cf53c5e5": {"__data__": {"id_": "631d2ae5-79a4-40cd-8d5d-21b7cf53c5e5", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.34, para 2](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "21e66974-e933-44f9-a83a-9464822f23bb", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.34, para 2](https://elifesciences.org/articles/95402)"}, "hash": "35a0e072fc02f3d06c5ff3d8b8287698a3ca440e0e0968cbe96d6c1991960069", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In the male, tdc-1(syb7768), tbh-1(syb7786), cat-1(syb6486), and oct-1(syb8870) animals also show reporter expression in the somatic gonad: while all four genes are expressed in the vas deferens, cat-1 and tbh-1, but not tdc-1 or oct-1, are expressed in the seminal vesicle (Figure 14C, Figure 8K). A similar pattern of cat-1(+); tbh-1(+); tdc-1(-); oct-1(-) is detected in several male-specific neurons and may indicate the usage of a novel transmitter (e.g. PEOH, see Discussion) by these cells. snf-3/BGT1 is also expressed in male somatic gonad cells, indicating that these cells could also use betaine for signaling (Figure 9E).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 633, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "72402bcb-8190-4dec-88b5-e6c33ad2bc5b": {"__data__": {"id_": "72402bcb-8190-4dec-88b5-e6c33ad2bc5b", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.34, para 3](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "18b3917f-0b44-43d6-9773-9e3a916da12c", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.34, para 3](https://elifesciences.org/articles/95402)"}, "hash": "c8812e961f9a28017998fa8badc967b9ae1ad4b949ec245b2c7b53852e331d5f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The AAADs tdc-1 and bas-1 are also prominently expressed in the intestine, where bas-1 has been shown to be involved in generating serotonin-derived glucosides (Yu et al., 2023). bas-1, but not tdc-1, is also expressed in the hypodermis and seam cells, as is the betaine uptake transporter snf-3 (Figure 9, Figure 14\u2014figure supplement 1). The tph-1 reporter allele expresses in a subset of pharyngeal non-neuronal cells during the L1 to L4 larval stages of development (Figure 6\u2014figure supplement 1), which is consistent with low levels of tph-1 transcripts detected in pharyngeal muscles in the CeNGEN scRNA dataset (Taylor et al., 2021). Additionally, we observed previously uncharacterized eat-4/VGLUT expression in muscle cells in both sexes (Figure 14D).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 759, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c03b02c2-d9bd-4dab-b63f-086055424ac2": {"__data__": {"id_": "c03b02c2-d9bd-4dab-b63f-086055424ac2", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.34, para 4](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d91a4e92-da82-4532-a0c0-e890f42f6f69", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.34, para 4](https://elifesciences.org/articles/95402)"}, "hash": "6e5b24c93849f14dc1c82ced8dc6db9337333febb53a87d6444103e3088b82d5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Discussion", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 13, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b968bf3c-46a6-4610-9663-2c2b7085d2ba": {"__data__": {"id_": "b968bf3c-46a6-4610-9663-2c2b7085d2ba", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.34, para 5](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2baf3e3f-9576-4720-83f7-aa49db959d6c", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.34, para 5](https://elifesciences.org/articles/95402)"}, "hash": "2fe132fca2bbb5c5564919cea2adfbafbbd55afd5bd8a46ade3ac435ee70e063", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Using CRISPR/Cas9-engineered reporter alleles we have refined and extended neurotransmitter assignments throughout all cells of the C. elegans male and hermaphrodite. We conclude that in both hermaphrodites and males, about one quarter of neurons are glutamatergic (eat-4/VGLUT-positive), a little more than half are cholinergic (unc-17/VAChT-positive), around 10% are GABAergic (unc-25/GAD-positive), and about another 10% are monoaminergic (cat-1/VMAT-positive). We compiled comprehensive lists for gene expression and neuron identities, which are provided in Supplementary file 2 for hermaphrodites and Supplementary file 3 for males. Figure 3 presents a summary of neurotransmitter usage and atlases showing neuron positions in worm schematics. Additionally, we summarize our rationale for assigning neurotransmitter usage and updates to previously reported data in Tables 1 and 2, and Supplementary file 5. Given the complexity and nuances in determining neurotransmitter usage, we refer the reader to all the individual tables for a comprehensive description of the subject matter, rather than encouraging sole reliance on the summary in Figure 3.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1153, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "77f147d6-6b0a-4de8-99ad-2cf23cb58f35": {"__data__": {"id_": "77f147d6-6b0a-4de8-99ad-2cf23cb58f35", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.34, para 6](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0e2577d4-cb0a-487c-933f-1558cc477774", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.34, para 6](https://elifesciences.org/articles/95402)"}, "hash": "b1def7edb7aa52e4d9b0766c25d9898549283f8252824a3cc3fc9f4cbf7339aa", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Neurotransmitter synthesis versus uptake", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 43, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "25a766c3-97f4-4ffb-a00f-e29010d8d804": {"__data__": {"id_": "25a766c3-97f4-4ffb-a00f-e29010d8d804", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.34, para 7](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "333e8d65-2754-4f5e-af05-42af80d7a9ab", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.34, para 7](https://elifesciences.org/articles/95402)"}, "hash": "36016faf22a6cba30998bc6cd1769057290ce3aed2c6f0d26b9232f045f9163e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Direct detection of neurotransmitters through antibody staining has shown that at least two neurotransmitters, GABA and serotonin, are present in some neurons that do not express the synthesis machinery for these transmitters (Tables 1 and 2). Instead, these neurons acquire GABA and serotonin through uptaking them via defined uptake transporters, SNF-11/BGT1 for GABA (Mullen et al., 2006) and MOD-5/SERT for serotonin (Ranganathan et al., 2001; Jafari et al., 2011). A combination of CeNGEN scRNA transcriptome and our reporter allele data corroborates the absence of synthesis machinery in these presumptive uptake neurons (Tables 1 and 2). One interesting question that relates to these uptake neurons is whether they serve as \u2018sinks\u2019 for clearance of a neurotransmitter or whether the taken-up neurotransmitter is subsequently \u2018recycled\u2019 for synaptic release via a vesicular transporter. Previous data, as well as our updated expression profiles, provide evidence for both scenarios: ALA and AVF do not synthesize GABA via UNC-25/GAD, but they stain with anti-GABA antibodies in a manner that is dependent on the uptake transporter SNF-11 (Gendrel et al., 2016). ALA expresses unc-47, hence it is likely to synaptically release GABA, but AVF does not, and it is therefore apparently involved only in GABA clearance. Similarly, RIH, AIM, and PGA express the serotonin uptake transporter mod-5/SERT and stain for serotonin in a MOD-5-dependent manner", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1454, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4f0bbcad-ed8c-47a7-b5df-7dd6045ffe8c": {"__data__": {"id_": "4f0bbcad-ed8c-47a7-b5df-7dd6045ffe8c", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.35, para 0](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bbbdd81a-489e-4fdb-bd87-bbdac0a79dd0", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.35, para 0](https://elifesciences.org/articles/95402)"}, "hash": "991b0849bfe6cbcc05e023aaee9ffc07b8e17c2f6de7f29b174f4d6e13072f97", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# eLife Tools and resources", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 27, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d3c62036-c2ba-4714-9392-0bf38c2dc5eb": {"__data__": {"id_": "d3c62036-c2ba-4714-9392-0bf38c2dc5eb", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.35, para 2](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e43bf6be-faf0-4395-875b-51d590780f97", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.35, para 2](https://elifesciences.org/articles/95402)"}, "hash": "6b9e6c00f7c8ec946a9a83e41aa7e5db0f5dac66322757e7669c09b7135006b0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "(Jafari et al., 2011) (this study), but only RIH and PGA, not AIM, expresses the vesicular transporter cat-1/VMAT, suggesting RIH and PGA are likely serotonergic signaling neurons whereas AIM is a clearance neuron.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 214, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2b894114-5451-4c75-a0c9-262f7ae5065d": {"__data__": {"id_": "2b894114-5451-4c75-a0c9-262f7ae5065d", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.35, para 3](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e08927da-1b02-4603-9060-366cbdb0db03", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.35, para 3](https://elifesciences.org/articles/95402)"}, "hash": "01d8c376e283aeee81ea64166328bfffc69640a2ee437cecb81e509edb6063d8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Some neurons do not obviously fall into the synthesis or uptake category, most notably, the anti-GABA-antibody-positive AVA and AVB neurons (both of which conventional cholinergic neurons). None of these neurons express unc-25/GAD, nor the snf-11/BGT1 uptake transporter, yet unc-25/GAD is required for their anti-GABA-positive staining (Gendrel et al., 2016). This suggests that GABA may be acquired by these neurons through non-canonical uptake or synthesis mechanisms. Also, the AVA and AVB neurons do not express UNC-47 (Gendrel et al., 2016; Taylor et al., 2021) (this study); hence, it is not clear if or how GABA is released from them. A member of the bestrophin family of ion channels has been shown to mediate GABA release from astrocyte glia in vertebrates (Lee et al., 2010) and, more recently, from C. elegans glia (Cheng et al., 2024; Graziano et al., 2024). However, while there are more than 20 bestrophin channels encoded in the C. elegans genome (Hobert, 2013), they do not appear to be expressed in the AVA or AVB neurons, based on CeNGEN scRNA data (Taylor et al., 2021).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1090, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "12bf8771-9ed0-44ef-8e27-abc9ddb92324": {"__data__": {"id_": "12bf8771-9ed0-44ef-8e27-abc9ddb92324", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.35, para 4](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b7ac51dc-ce5b-40db-ba19-c585d7eba67d", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.35, para 4](https://elifesciences.org/articles/95402)"}, "hash": "53f9a8b357aa982696f127ca5ef4408db2cdf21c23b67c29ec70d5d8b42003ac", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The co-expression of a specific uptake transporter and a vesicular transporter corroborates the potential usage of betaine as a neurotransmitter. Betaine is known to be synthesized in C. elegans but is also taken up via its diet (Peden et al., 2013; Hardege et al., 2022). Betaine has documented effects on C. elegans behavior and acts via activation of several betaine-gated ion channels (Peden et al., 2013; Hardege et al., 2022). Expression of biosynthetic enzymes suggests betaine production in at least the RIM neuron class, which also expresses the vesicular transporter cat-1/VMAT, capable of transporting betaine (Hardege et al., 2022). The expression of the betaine uptake transporter snf-3/BGT1 in CAN, AUA, RIR, ASI, and male-specific neuron PDC, coupled with their co-expression of cat-1/VMAT, suggests that several distinct neuron classes in different parts of the nervous system may uptake betaine and engage in vesicular betaine release via CAT-1/VMAT to gate betaine-activated ion channels, such as ACR-23 (Peden et al., 2013) or LGC-41 (Hardege et al., 2022). Additionally, we detected the snf-3/BGT1 reporter allele in several other neuron classes that do not co-express cat-1/VMAT. This indicates that these neurons could function as betaine clearance neurons.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1279, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "45472e7a-552d-4cb7-b2cd-40940161590c": {"__data__": {"id_": "45472e7a-552d-4cb7-b2cd-40940161590c", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.35, para 5](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a5ef6103-3782-405f-8664-5b423d190936", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.35, para 5](https://elifesciences.org/articles/95402)"}, "hash": "0c5d5feeffadd32372413fde661f08bee357e9593ec584720ec6ffd8dfc988f9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Lastly, based on sequence similarity and expression pattern, we predict that the ortholog of the OCT subclass of SLC22 family, oct-1, could serve as a tyramine uptake transporter in C. elegans. We identified RIM as the only neuron expressing an oct-1 reporter allele, suggesting that like several other monoaminergic neuron classes, RIM both synthesizes its monoaminergic transmitter and reuptakes it after release.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 415, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e1721b6c-052e-44cb-a71f-2eda0251be44": {"__data__": {"id_": "e1721b6c-052e-44cb-a71f-2eda0251be44", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.35, para 6](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "24effd9c-7ec4-44db-abda-3ddced5917e4", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.35, para 6](https://elifesciences.org/articles/95402)"}, "hash": "b80c1d17f9d4204acd7bbe5cda925c7e8e96aad6502774c27cbd57e6a3b26b80", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Evidence for usage of currently unknown neurotransmitters", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 60, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "90e3e5a7-a892-412a-bba1-92f88cbe6be2": {"__data__": {"id_": "90e3e5a7-a892-412a-bba1-92f88cbe6be2", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.35, para 7](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e8f3c0e0-10da-4c91-9b96-e350c2556f56", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.35, para 7](https://elifesciences.org/articles/95402)"}, "hash": "b18b44f264a72e89dbc8b8e55b259f5ddc13783e92cdc335f263468faa0577b9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Novel amino acid transmitters?", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 34, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3448d3e2-59fc-4782-82db-b244f43877f8": {"__data__": {"id_": "3448d3e2-59fc-4782-82db-b244f43877f8", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.35, para 8](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0dccbcd2-0c0d-4b89-beda-56fe226095be", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.35, para 8](https://elifesciences.org/articles/95402)"}, "hash": "d3ed3a1dabdbfc64fd78ec0ad1498e839f47c0fb9942e1466bb3fa67bbbd4cc8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "unc-47/VGAT is expressed in a substantial number of non-GABAergic neurons (95 out of 302 total neurons in hermaphrodites, plus 61 out of 93 male-specific neurons). However, expression in many of these non-GABAergic neurons is low and variable and such expression may not lead to sufficient amounts of a functional gene product. Yet, in some neurons (e.g. the SIA neurons) expression of unc-47 is easily detectable and robust (based on fosmid-based reporter, reporter allele, and scRNA data), indicating that VGAT may transport another presently unknown neurotransmitter (Gendrel et al., 2016). In vertebrates, VGAT transports both GABA and glycine, and the same is observed for UNC-47 in vitro (Aubrey et al., 2007). While the C. elegans genome encodes no easily recognizable ortholog of known ionotropic glycine receptors, it does encode anion channels that are closely related by primary sequence (Hobert, 2013). Moreover, a recently identified metabotropic glycine receptor, GPR158 (Laboute et al., 2023), has a clear sequence ortholog in C. elegans, F39B2.8. Therefore, glycine may also act as a neurotransmitter in C. elegans. VGAT has also been shown to transport \u03b2-alanine (Juge et al., 2013), another potential, but as yet unexplored, neurotransmitter in C. elegans. However, it needs to be pointed out that most of the additional unc-47-positive neurons do not co-express the LAMP-type UNC-46 protein, which is important for sorting UNC-47/VGAT to synaptic vesicles in conventional GABAergic neurons (Schuske et al., 2007). In vertebrates, the functional UNC-46 ortholog LAMP5 is only expressed and required for VGAT transport in a subset of VGAT-positive, GABAergic neurons (Tiveron et al., 2016; Koebis et al., 2019), indicating that alternative vesicular sorting mechanisms exist for UNC-47/VGAT.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1808, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5ec5a780-7c65-48df-a77d-0f991af37b16": {"__data__": {"id_": "5ec5a780-7c65-48df-a77d-0f991af37b16", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.36, para 1](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5d2dd45f-9752-4255-8c13-54d0f62fe79f", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.36, para 1](https://elifesciences.org/articles/95402)"}, "hash": "71b3c222cb4d6f678872ee4cddd97ec9aa5f729ce7b220a4db005510f6b0baa3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Novel monoaminergic transmitters?", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 35, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5587e205-eef0-4870-9756-8e61e084d7a0": {"__data__": {"id_": "5587e205-eef0-4870-9756-8e61e084d7a0", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.36, para 2](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fa2a1cbf-3e58-4cb0-8298-d57ef0616740", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.36, para 2](https://elifesciences.org/articles/95402)"}, "hash": "5f9f0544239fc4e2100c717b57ab1293d378d85219cf4b924542819e9115d96d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Three neuron classes (AVL, PVX, and PVY) express cat-1/VMAT but do not express the canonical synthesis machinery for serotonin, tyramine, octopamine, or dopamine. Neither do they show evidence for uptake of known monoamines. There are also several cat-1/VMAT-positive male-specific neurons that express only a subset of the biosynthetic machinery involved in the biosynthesis of known aminergic transmitters in the worm. That is, some neurons express cat-1/VMAT and bas-1/AAAD, but none of the previously known enzymes that produce the substrate for BAS-1, i.e., CAT-2 or TPH-1 (Figure 1A). In these neurons, BAS-1/AAAD may decarboxylate an unmodified (i.e. non-hydroxylated) aromatic amino acid as substrate to produce, for example, the trace amine PEA from phenylalanine (Table 2, Figure 1\u2014figure supplement 1A). A subset of these neurons (all being B-type ray sensory neurons) co-express tbh-1, which may use PEA as a substrate to produce the trace amine, PEOH. PEOH is a purported neurotransmitter in Aplysia (Saavedra et al., 1977) and the vertebrate brain (Saavedra and Axelrod, 1973) and can indeed be detected in C. elegans extracts (F Schroeder, pers. comm.).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1168, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a0dc9412-b011-46fc-b070-55c141421ffb": {"__data__": {"id_": "a0dc9412-b011-46fc-b070-55c141421ffb", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.36, para 3](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7420115f-4d21-45ef-bec4-bb8f2e8ea159", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.36, para 3](https://elifesciences.org/articles/95402)"}, "hash": "e8d1f3ad55e3402eec6acb0f0ce58cf0059586032cbb9e2f93cefcc83dced719", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "bas-1/AAAD may also be responsible for the synthesis of histamine, an aminergic neurotransmitter that can be found in extracts of C. elegans (Pertel and Wilson, 1974). The only other AAAD that displays reasonable sequence similarity to neurotransmitter-producing AAADs is the hdl-1 gene (Hare and Loer, 2004; Hobert, 2013; Figure 1\u2014figure supplement 1B), for which we, however, did not detect any expression in the C. elegans nervous system (Figure 1\u2014figure supplement 1C and D). Since there are neurons that only express bas-1/AAAD, but no enzyme that produces canonical substrates for bas-1/AAAD (tph-1/TPH, cat-2/TH; Figure 1A), and since at least a subset of these neurons express the monoamine transporter cat-1/VMAT (Table 2), bas-1/AAAD may be involved in synthesizing another currently unknown bioactive monoamine.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 822, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8c68ab3e-fbe7-4cd0-8127-7b8033957e65": {"__data__": {"id_": "8c68ab3e-fbe7-4cd0-8127-7b8033957e65", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.36, para 4](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "469cd10d-54f0-4faa-a431-3191324a93f3", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.36, para 4](https://elifesciences.org/articles/95402)"}, "hash": "711bb7057fcda201efb9e3df910801066775af1c87e9a0882078e2b055427bf4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Conversely, based on the expression of tph-1, but concurrent absence of bas-1/AAAD, the pharyngeal MI neuron, hermaphrodite VC4 and VC5, and male neurons CEM and R9B may produce 5-HTP (Table 2). 5-HTP may either be used directly as a signaling molecule or it may be metabolized into some other serotonin derivative, an interesting possibility in light of serotonin derivatives produced elsewhere in the body (Yu et al., 2023).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 426, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "643f5375-a1f7-463f-a3db-e6b2ab7473fb": {"__data__": {"id_": "643f5375-a1f7-463f-a3db-e6b2ab7473fb", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.36, para 5](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cfa6aa3d-9161-4820-a3b1-408cfd9094a7", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.36, para 5](https://elifesciences.org/articles/95402)"}, "hash": "c37cae6f648f9ab499a0c63fbaa3a513eddc53e4595e1c1322b41dcd4d0614d3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Additionally, three neuron classes (IL2, HOB, and R5B) express tbh-1 but lack expression of any other genes in canonical monoaminergic pathways, including bas-1 (Table 2). Taken together, canonical monoaminergic pathway genes are expressed in unconventional combinations in several neuron classes, pointing toward the existence of yet undiscovered amino acid-derived neuronal signaling systems.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 394, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0d599e85-4f8a-453b-8695-97f03ce17e07": {"__data__": {"id_": "0d599e85-4f8a-453b-8695-97f03ce17e07", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.36, para 6](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7e524862-27d1-4698-9ca4-743808647c8e", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.36, para 6](https://elifesciences.org/articles/95402)"}, "hash": "1c4930f55efad9af5f6b76909f11a254823b717355803a85670c6505bb33a222", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Neurons devoid of canonical neurotransmitter pathway genes may define neuropeptide-only neurons", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 98, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c8edd117-7b19-41dc-9f9f-673940dfa472": {"__data__": {"id_": "c8edd117-7b19-41dc-9f9f-673940dfa472", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.36, para 7](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ac2b6f88-e9b6-4a86-a57c-1b509bd58d7b", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.36, para 7](https://elifesciences.org/articles/95402)"}, "hash": "d72318f65e853ee74d24ad13e11c4205ace56968d4822ac4eefbb611c2b7bd1c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We identified neurons that do not express any conventional, well-characterized vesicular neurotransmitter transporter families, namely UNC-17/VAChT, CAT-1/VMAT (the only SLC18 family members), UNC-47/VGAT (only SLC32 family member), or EAT-4/VGLUT (an SLC17 family member). Six sex-shared neurons (AVH, BDU, PVM, PVQ, PVW, RMG) and one male-specific neuron (SPD) fall into this category. Most of these neurons exhibit features that are consistent with them being entirely neuropeptidergic. First, electron microscopy has revealed a relative paucity of clear synaptic vesicles in most of these neurons (White et al., 1986; Cook et al., 2019; Witvliet et al., 2021). Second, not only do these neurons express a multitude of neuropeptide-encoding genes (Taylor et al., 2021), but they also display a dense interconnectivity in the \u2018wireless\u2019 neuropeptidergic connectome (Ripoll-S\u00e1nchez et al., 2023).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 897, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "622de40b-e112-447f-a297-7480c0445406": {"__data__": {"id_": "622de40b-e112-447f-a297-7480c0445406", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.36, para 8](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f6b7abfa-eb2f-48a7-bda8-139d7dd4f072", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.36, para 8](https://elifesciences.org/articles/95402)"}, "hash": "0200ef661254e52497c75eee36471762bccae4a37797caeaa021e628269d7e76", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "That said, electron microscopy shows that some of the neurons devoid of conventional neurotransmitter pathway genes generate synapses with small, clear synaptic vesicles, indicative of the use of non-peptidergic transmitters (e.g. the sex-shared RMG and PVM neurons or the male-specific SPD neurons) (White et al., 1986; Cook et al., 2019; Witvliet et al., 2021). It is therefore conceivable that either conventional neurotransmitters utilize non-conventional neurotransmitter synthesis and/or release pathways, or that completely novel neurotransmitter systems remain to be discovered. Although the C. elegans genome does not encode additional members of the SLC18A2/3 (cat-1/VMAT, unc-17/VAChT) or SLC32A1 (unc-47/VGAT) family of vesicular neurotransmitter transporters, it does contain a number of additional members of the SLC17A6/7/8 (VGLUT) family (Hobert, 2013).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 869, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f51f38a0-9ebf-4eda-a394-1ed42c67c184": {"__data__": {"id_": "f51f38a0-9ebf-4eda-a394-1ed42c67c184", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.37, para 1](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a6ab2bf6-3e7b-4f3f-af53-518f4fdd5e98", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.37, para 1](https://elifesciences.org/articles/95402)"}, "hash": "c8c6571a6bc45b89e910797b32a7610c86f4fb06a244445c3552a1e4ef25b691", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "These may serve as non-canonical vesicular transporters of more uncommon neurotransmitters or, alternatively, may be involved in modulating release of glutamate (Serrano-Saiz et al., 2020; Choi et al., 2021). Uncharacterized paralogs of bona fide neurotransmitter uptake transporters (SLC6 superfamily) may also have functions in neurotransmitter release rather than uptake. However, based on CeNGEN scRNA data, no robust or selective expression of these SLC17 or SLC6 family members is observed in these \u2018orphan neurons\u2019.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 522, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b5ae6e4c-0cd9-4301-8eb2-1d9ff206fcb4": {"__data__": {"id_": "b5ae6e4c-0cd9-4301-8eb2-1d9ff206fcb4", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.37, para 2](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5077eba4-9c9b-4959-b63f-a20bd7035705", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.37, para 2](https://elifesciences.org/articles/95402)"}, "hash": "a60b51051c7f2f092b6646dcc0149a43d1ac7c7ef395f7b10edf50f262782ff3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Co-transmission of multiple neurotransmitters", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 48, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "30cdbfc3-b23f-43c3-bbb6-90565fb550e2": {"__data__": {"id_": "30cdbfc3-b23f-43c3-bbb6-90565fb550e2", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.37, para 3](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3d825541-31e8-4cd3-ab6c-adb0019efcb1", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.37, para 3](https://elifesciences.org/articles/95402)"}, "hash": "579b61b34613fb9bb18be17d2c5ee142ae7ed31c08f4c0d5f80b77365d634592", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Our analysis expands the repertoire of neurons that co-transmit multiple neurotransmitters (Figure 3). Neurotransmitter co-transmission has been observed in multiple combinations in the vertebrate brain (Wallace and Sabatini, 2023). In *C. elegans*, the most frequent co-transmission configurations are a classic, fast transmitter (acetylcholine or glutamate) with a monoamine. Co-transmission of two distinct monoaminergic systems also exists. In several cases, however, it is not clear whether the second neurotransmitter is indeed used for communication or whether its presence is merely a reflection of this neuron being solely a clearance neuron. For example, the glutamatergic AIM neuron stains positive for serotonin, which it uptakes via the uptake transporter MOD-5, but it does not express the vesicular monoamine transporter cat-1/VMAT (Figures 3, 6, and 8, Tables 1 and 2).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 885, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fc0780ce-5131-4976-99db-8b89375ad263": {"__data__": {"id_": "fc0780ce-5131-4976-99db-8b89375ad263", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.37, para 4](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f791be35-f1e4-43ae-a710-fc1fe981ec33", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.37, para 4](https://elifesciences.org/articles/95402)"}, "hash": "f1f63dc4e89b7fe50de89520a32c9311f63a4d5342d9b76cdba6b4f7d33c3ee1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Co-transmission of small, fast-acting neurotransmitters (glutamate, GABA, acetylcholine) does exist, but it is rare (Figure 3). The most prominent co-transmission configuration is acetylcholine with glutamate, but acetylcholine can also be co-transmitted with GABA. There are no examples of co-transmission of glutamate and GABA, as observed in several regions of the vertebrate brain (Wallace and Sabatini, 2023). There are also examples of possible co-transmission of three transmitters (Figure 3).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 500, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7146972a-88e9-4fed-b866-71f52d7cc8a2": {"__data__": {"id_": "7146972a-88e9-4fed-b866-71f52d7cc8a2", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.37, para 5](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f7d20345-ac72-41d2-9d0d-404c2bec709d", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.37, para 5](https://elifesciences.org/articles/95402)"}, "hash": "fb5aa1885771aad39d5025e12b63c0fa4622760ceddf367858a5d624e67693a1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Interestingly, co-transmission appears to be much more prevalent in the male-specific nervous system, compared to the sex-shared nervous system (Figure 3, Supplementary file 3). This may relate to male-specific neurons displaying a greater degree of anatomical complexity compared to the hermaphrodite nervous system, both in terms of branching patterns and extent of synaptic connectivity (Jarrell et al., 2012; Cook et al., 2019). Given that all co-transmitting neurons display multiple synaptic outputs (Cook et al., 2019), it appears possible that each individual neurotransmitter secretory system is distributed to distinct synapses. Based on vertebrate precedent (Wallace and Sabatini, 2023), co-release from the same vesicles is also possible.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 750, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e60ea722-2f33-40d2-9edf-b58b874dfd4e": {"__data__": {"id_": "e60ea722-2f33-40d2-9edf-b58b874dfd4e", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.37, para 6](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5e563c6a-71da-4da5-8b2c-549ea0101a3b", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.37, para 6](https://elifesciences.org/articles/95402)"}, "hash": "d05681a1654857dd3e529d52b11abe98b7a9ac8eb0bb7d8dd97ee0d2f9bda1a8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Sexual dimorphisms in neurotransmitter usage", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 47, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cdbfbb2c-be56-4b0d-a55c-8c7464ff119c": {"__data__": {"id_": "cdbfbb2c-be56-4b0d-a55c-8c7464ff119c", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.37, para 7](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a8a2eda3-625e-4c7f-a55b-109b788fca8a", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.37, para 7](https://elifesciences.org/articles/95402)"}, "hash": "78d418551aa7019ccb75aaed8249fd8b27bd42cd5fd2e2bfc221b06de788353d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The observation of sexual dimorphisms in neurotransmitter abundance in specific regions of the mammalian brain has been one of the earliest molecular descriptors of neuronal sex differences in mammals (McCarthy et al., 1997). However, it has remained unclear whether such differences are the result of the presence of sex-specific neurons or are indications of distinctive neurotransmitter usage in sex-shared neurons. Using *C. elegans* as a model, we have been able to precisely investigate (a) whether sex-specific neurons display a bias in neurotransmitter usage and (b) whether there are neurotransmitter dimorphisms in sex-shared neurons (Pereira et al., 2015; Gendrel et al., 2016; Serrano-Saiz et al., 2017b) (this paper). We found that male-specific neurons display a roughly similar proportional usage of individual neurotransmitter systems and note that male-specific neurons display substantially more evidence of co-transmission, a possible reflection of their more elaborate morphology and connectivity. We also confirmed evidence for sexual dimorphisms in neurotransmitter usage in sex-shared neurons (Supplementary file 4), which are usually correlated with sexual dimorphisms in synaptic connectivity of these sex-shared neurons (Cook et al., 2019).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1266, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "74c38c14-39e1-496f-ba5a-0698011b201d": {"__data__": {"id_": "74c38c14-39e1-496f-ba5a-0698011b201d", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.37, para 8](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "848c5fae-27cd-4abe-a286-ee37a7bbc8c1", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.37, para 8](https://elifesciences.org/articles/95402)"}, "hash": "91e305a8ddef0d9ba89c5b90aa20f9f060bec6e136f032f45f745ff0d7507343", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Neurotransmitter pathway genes in glia and gonad", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 51, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b440fa5c-9cb3-48a4-84d6-93e01a1de831": {"__data__": {"id_": "b440fa5c-9cb3-48a4-84d6-93e01a1de831", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.37, para 9](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "62fe7a5a-24bc-4bf0-8550-8aa1c4c8310c", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.37, para 9](https://elifesciences.org/articles/95402)"}, "hash": "5f0a6668204650a0fc95d1e4eb8e3866f2af3190a0a951c0e197bdc6ab469400", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Neurotransmitter uptake is a classic function of glial cells across animal phylogeny (Henn and Hamberger, 1971), and such uptake mechanisms are observed in *C. elegans* as well. Previous reports demonstrated glutamate uptake by CEPsh (Katz et al., 2019) and GABA uptake by GLR glia (Gendrel et al., 2016). We now add to this list betaine uptake by most glia, as inferred from the expression pattern of SNF-3/BGT1 (Figure 9, Supplementary file 1).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 446, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7a0009b4-3255-44aa-a59e-c88030797d24": {"__data__": {"id_": "7a0009b4-3255-44aa-a59e-c88030797d24", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.37, para 10](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "623847d9-7828-441b-a3d8-2ae08cdf462f", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.37, para 10](https://elifesciences.org/articles/95402)"}, "hash": "79c52b0a7114c48d67fb306d4cd7276a47e3b8b75c1d5439bd76c0f1a8a30d28", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Studies in vertebrates have also suggested that specific glial cell types synthesize and release several neurotransmitters (Araque et al., 2014; Savtchouk and Volterra, 2018). For example,", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 188, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "06953dcf-bffe-49c2-9f0c-360ade54c326": {"__data__": {"id_": "06953dcf-bffe-49c2-9f0c-360ade54c326", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.38, para 0](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7d423fa0-679f-4aac-a65e-09dc0d1a498f", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.38, para 0](https://elifesciences.org/articles/95402)"}, "hash": "a293dfc758f8199acc8cdfb092a3cf98d54fd6fa26c4a7bd4134ff82de4f9088", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# eLife Tools and resources", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 27, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "055b8566-b4b3-4961-b629-0169a50c4282": {"__data__": {"id_": "055b8566-b4b3-4961-b629-0169a50c4282", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.38, para 2](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "48029994-dc10-4aa7-b512-fc34ecc01807", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.38, para 2](https://elifesciences.org/articles/95402)"}, "hash": "3ea249632340228e124697125eb00e3e55b181a31cd6eaa8a88456decfdce367", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "astrocytes were recently shown to express VGLUT1 to release glutamate (de Ceglia et al., 2023). Evidence of neurotransmitter synthesis and release also exists in C. elegans glia. Previous work indicated that glia associated with male-specific spicule neurons synthesize (through cat-2/TH and bas-1/AAAD) the monoaminergic transmitter dopamine to control sperm ejaculation (LeBoeuf et al., 2014). Our identification of cat-1/VMAT expression in these glia indicate that dopamine is released via the canonical vesicular monoamine transporter. We also detected expression of bas-1/AAAD in additional male and hermaphrodite glia, indicating the production of other signaling substances released by these glia. bas-1 has indeed recently been shown to be involved in the synthesis of a class of unconventional serotonin derivatives (Yu et al., 2023).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 843, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9a5c9354-48cf-46f7-a20d-5e31f81d5f8f": {"__data__": {"id_": "9a5c9354-48cf-46f7-a20d-5e31f81d5f8f", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.38, para 3](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "695030ab-67e9-468a-b2fc-386552f0cb3d", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.38, para 3](https://elifesciences.org/articles/95402)"}, "hash": "4f7cf20063f3838722cf87431b834c9540af66f5d93b78c6bf8683c25b623280", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "There have been previous reports on GABA synthesis and release from the AMsh glial cell type (Duan et al., 2020; Fernandez-Abascal et al., 2022). We were not able to detect AMsh with anti-GABA staining, nor with reporter alleles of unc-25/GAD. However, since very low levels of unc-25 are observed in the AMsh scRNA datasets (Taylor et al., 2021; Purice et al., 2023), the abundance of GABA in AMsh may lie below conventional detection levels.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 443, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8095f92e-1f94-4b29-a39f-df814ae1490c": {"__data__": {"id_": "8095f92e-1f94-4b29-a39f-df814ae1490c", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.38, para 4](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3abd9a74-548b-4391-9ef3-5fd54751ed6f", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.38, para 4](https://elifesciences.org/articles/95402)"}, "hash": "b9a849d21baa4569a4948c914cef7f0f6810b680f364dff5929b9e4d1fd069e9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Outside the nervous system, the most prominent and functionally best characterized usage of neurotransmitters lies in the hermaphrodite somatic gonad, which has been shown to synthesize octopamine and use it to control oocyte quiescence (Alkema et al., 2005; Kim et al., 2021). Intriguingly, we also detected tbh-1, tdc-1, and cat-1 expression in the somatic gonad of the male, specifically the vas deferens, which is known to contain secretory granules that are positive for secretory molecular markers (Nonet et al., 1993). The presence of octopamine is unexpected because, unlike oocytes, sperm are not presently known to require monoaminergic signals for any aspect of their maturation. It will be interesting to assess sperm differentiation and function of tbh-1 or tdc-1 mutant animals. The usage of monoaminergic signaling systems in the gonad is not restricted to C. elegans and has been discussed in the context of sperm functionality and oocyte maturation in vertebrates (Mayerhofer et al., 1999; Ram\u00edrez-Reveco et al., 2017; Alhajeri et al., 2022).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1059, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ba2c2b2c-fcc0-4742-a26a-c8432c536e8e": {"__data__": {"id_": "ba2c2b2c-fcc0-4742-a26a-c8432c536e8e", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.38, para 5](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "def8bbdb-6392-4f26-b308-34369fc809af", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.38, para 5](https://elifesciences.org/articles/95402)"}, "hash": "7e5d5304cdf85e2a3182273a916a3ebcaf502bfc0bdb8804e8cdbddfac73df82", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Comparing approaches and caveats of expression pattern analysis", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 66, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ebb20dd3-5d4e-4dd8-a488-a3401bf8797b": {"__data__": {"id_": "ebb20dd3-5d4e-4dd8-a488-a3401bf8797b", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.38, para 6](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c71cb313-9629-4d42-851a-ccab1f33d701", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.38, para 6](https://elifesciences.org/articles/95402)"}, "hash": "d89fe9bc2132132ae912aea67782011a97d4f0a08456ff7fcf60f4d4ba17dcc1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Our analysis also provides an unprecedented and systematic comparison of antibody staining, scRNA transcript data, reporter transgene expression, and knock-in reporter allele expression. The bottom-line conclusions of these comparisons are: (1) Reporter alleles reveal more sites of expression than fosmid-based reporters. It is unclear whether this is due to the lack of cis-regulatory elements in fosmid-based reporters or issues associated with the multicopy nature of these reporters (e.g. RNAi-based gene silencing of multicopy arrays or squelching of regulatory factors). Another factor to consider is that neuron identification for most fosmid-based reporters was carried out prior to the introduction of NeuroPAL. Consequently, errors occasionally occurred, as exemplified by the misidentification of neuron IDs for CA7 and CP7 in previous instances (Serrano-Saiz et al., 2017b). (2) The best possible reporter approaches (i.e. reporter alleles) show very good overlap with scRNA data, thereby validating each approach. However, our comparisons also show that no single approach is perfect. CeNGEN scRNA data can miss transcripts and can also show transcripts in cells in which there is no independent evidence for gene or protein expression. Conversely, antibody staining displays vagaries related to staining protocols and protein localization, which can be overcome with reporter approaches, but the price to pay with reporter alleles is that if they are based on SL2 or T2A strategies, they may fail to detect additional levels of posttranslational regulation, which may result in protein absence even in the presence of transcripts. The existence of such mechanisms may be a possible explanation for cases where the expression of synthesis and/or transport machinery expression does not match up (e.g. tdc-1(-); tbh-1(+) neurons).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1843, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "daf29d5a-44ce-4d8e-bcbd-8d31df790da0": {"__data__": {"id_": "daf29d5a-44ce-4d8e-bcbd-8d31df790da0", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.38, para 7](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9ac1938d-e761-4182-aa6f-f5446f93d34f", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.38, para 7](https://elifesciences.org/articles/95402)"}, "hash": "db55276d98346def3a6b6e96f7e34c6db224082045d5f1e990543979c4171996", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Our detailed analysis of reporter allele expression has uncovered several cases where expression of a neurotransmitter pathway gene in a given neuron class appears very low and variable from animal to animal. Such variability only exists when expression is dim, thus one possible explanation for it is that expression levels merely hover around an arbitrary microscopical detection limit. However, we cannot rule out the other possibility that this may also reflect true on/off variability of gene expression. Taking this notion a step further, we cannot exclude the possibility that expression observed with reporter alleles misses sites of expression. This possibility is raised by our inability to detect unc-25/GAD reporter allele expression in AMsh glia (Duan et al., 2020; Fernandez-Abascal et al., 2022) or eat-4 reporter allele expression in AVL and DVB neurons, in which some (but not other) multicopy", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 910, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "eac3c7b6-54a7-4a31-866d-173023c27ef1": {"__data__": {"id_": "eac3c7b6-54a7-4a31-866d-173023c27ef1", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.39, para 1](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fd52e2bc-8546-42f8-aab2-2ad6e7f178b5", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.39, para 1](https://elifesciences.org/articles/95402)"}, "hash": "419e8e30ce0bba9d6240648b27dfd2312c5da60948793cb8ecce56c6e823f38c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "reporter transgenes revealed expression of the respective genes (*Li et al., 2023*). Functions of these genes in the respective cell types were corroborated by cell-type-specific RNAi experiments and/or rescue experiments; whether there is indeed very low expression of these genes in those respective cells or whether drivers used in these studies for knock-down and/or rescue produce very low expression in other functionally relevant cells remains to be resolved.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 466, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3397f368-f5f8-4ee3-883c-e871cddbdee8": {"__data__": {"id_": "3397f368-f5f8-4ee3-883c-e871cddbdee8", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.39, para 2](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6762bb42-a9a9-40f4-ba74-41e25c93d468", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.39, para 2](https://elifesciences.org/articles/95402)"}, "hash": "6ecc9a80d1da23c1cb15af0ea9b9888dc4e77894ed2d673e5310497040172447", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Conclusions", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 14, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "59464975-7288-4d0e-8a92-3db3b88332a7": {"__data__": {"id_": "59464975-7288-4d0e-8a92-3db3b88332a7", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.39, para 3](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2450ab87-8813-40a7-9809-c4e7c34fff39", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.39, para 3](https://elifesciences.org/articles/95402)"}, "hash": "1b902c20e5ca2b12d4b80f29376780d73ded875721b45aaf9da3964940738549", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In conclusion, we have presented here the most complete neurotransmitter map that currently exists for any animal nervous system. Efforts to map neurotransmitter usage on a system-wide level are underway in other organisms, most notably, *Drosophila melanogaster* (*Deng et al., 2019; Eckstein et al., 2024*). The *C. elegans* neurotransmitter map presented here comprises a critical step toward deciphering information flow in the nervous system and provides valuable tools for studying the genetic mechanisms underlying cell identity specification. Moreover, this neurotransmitter map opens new opportunities for investigating sex-specific neuronal differentiation processes, particularly in the male-specific nervous system, where a scarcity of molecular markers has limited the analysis of neuronal identity control. Lastly, our analysis strongly suggests that additional neurotransmitter systems remain to be identified.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 925, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6502e611-5239-4d5d-9a0b-a6c39e9c92cc": {"__data__": {"id_": "6502e611-5239-4d5d-9a0b-a6c39e9c92cc", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.39, para 4](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b45b2669-3e75-42e2-9cdc-fda36176dd4e", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.39, para 4](https://elifesciences.org/articles/95402)"}, "hash": "7bee3e1fc09810cfb21d747a23e8954c43dddf0f0c8e38e220e3a083e7f4f8a2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "While the gene expression patterns delineated here enable informed predictions about novel neuronal functions and neurotransmitter identities, further investigations involving genetic perturbations, high-resolution imaging, complementary functional assays, and analyses across developmental stages are needed to shed further light on neurotransmitter usage. Nonetheless, this comprehensive neurotransmitter map provides a robust foundation for deciphering neural information flow, elucidating developmental mechanisms governing neuronal specification, exploring sexual dimorphisms in neuronal differentiation, and potentially uncovering novel neurotransmitter systems awaiting characterization.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 694, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3f9bd119-9220-4ff3-bd0b-b391f3739fb0": {"__data__": {"id_": "3f9bd119-9220-4ff3-bd0b-b391f3739fb0", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.39, para 5](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8cb0c337-21c2-4927-89aa-49ba8db8129c", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.39, para 5](https://elifesciences.org/articles/95402)"}, "hash": "c73416357e4f7b7bde2db23eb0287a2811a3a629de6c8c2ea964417200b8f72a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Materials and methods", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 24, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "518d8cae-96a2-450e-b1e3-f63b9d014f1f": {"__data__": {"id_": "518d8cae-96a2-450e-b1e3-f63b9d014f1f", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.39, para 6](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8293bc7b-f8c5-48b0-9132-a37d6ae1dedc", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.39, para 6](https://elifesciences.org/articles/95402)"}, "hash": "c4762249b9aef82a27951f1c5cae664ebc6b54b5f727bc4e5396be1e9b869baf", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Transgenic reporter strains", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 31, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e098dcce-2cd1-418d-bf4a-9a4a862d4b0a": {"__data__": {"id_": "e098dcce-2cd1-418d-bf4a-9a4a862d4b0a", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.39, para 7](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "78da7488-e45a-458b-ae12-b6e59f223b74", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.39, para 7](https://elifesciences.org/articles/95402)"}, "hash": "33244752ec7dbe5fe8e4c8932f066d536b31656d61fc3529eadd5623bd44eddd", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Knock-in reporter alleles were generated either by SunyBiotech (syb alleles) or in-house (ot alleles) using CRISPR/Cas9 genome engineering. Most genes were tagged with a nuclear-targeted gfp sequence (gfp fused to his-44, a histone h2b gene) at the 3' end of the locus to capture all isoforms, except tdc-1 which was tagged at the 5' end. For unc-25, both isoforms were individually tagged since a single tag would not capture both. Transgene schematics are shown in Figure 2.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 476, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "000d1ebf-3e8c-412f-8251-3353e0733221": {"__data__": {"id_": "000d1ebf-3e8c-412f-8251-3353e0733221", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.39, para 8](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7f60f443-5cb7-4b3a-a8e1-94ef668cebc8", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.39, para 8](https://elifesciences.org/articles/95402)"}, "hash": "2a56efaf73970f9d1de3cc15c1a45957e535c3d5b2350b57ac057cce6b52337c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Reporter alleles generated in this study:", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 41, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ca300d25-75b9-4735-af0a-5e38cf405bbe": {"__data__": {"id_": "ca300d25-75b9-4735-af0a-5e38cf405bbe", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.39, para 9](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "41cf8da1-f291-4fcc-a6ae-ef1758bd87dc", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.39, para 9](https://elifesciences.org/articles/95402)"}, "hash": "e8bd1cc4103177c77a33ad65ec5b0d0ccbaa7cfcca5cdc1bff0d20246d9e93f8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* unc-25(ot1372\\[unc-25a.1c.1::t2a:gfp::h2b]) III\n* unc-25(ot1536\\[unc-25b.1::t2a::gfp::h2b]) III\n* unc-46(syb7278\\[unc-46::sl2::gfp:h2b]) V\n* unc-47(syb7566\\[unc-47::sl2::gfp::h2b]) III\n* cat-1(syb6486\\[cat-1::sl2::gfp::h2b]) X\n* tph-1(syb6451\\[tph-1::sl2::gfp::h2b]) II\n* tbh-1(syb7786\\[tbh-1::sl2::gfp::h2b]) X\n* tdc-1(syb7768\\[gfp::linker::h2b::t2a::tdc-1]) II\n* cat-2(syb8255\\[cat-2::sl2::gfp::h2b]) II\n* snf-3(syb7290\\[snf-3::TagRFP::sl2::gfp::h2b]) II\n* oct-1(syb8870\\[oct-1::sl2::gfp::h2b]) I\n* hdl-1(syb1048\\[hdl-1::gfp]) IV\n* hdl-1(syb4208\\[hdl-1::t2a::3xnls::cre]) IV", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 578, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "defb5fb5-7d2e-49b1-8f5e-1fcb8eab6735": {"__data__": {"id_": "defb5fb5-7d2e-49b1-8f5e-1fcb8eab6735", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.39, para 10](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1d19ae68-d356-40f7-b5f3-fea3247b30cc", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.39, para 10](https://elifesciences.org/articles/95402)"}, "hash": "2cf6c16abe916314f099d4e209a28ab9461c1017415adbca29731fa1acbcd171", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Since we did not detect fluorophore signals in the hdl-1(syb1048\\[hdl-1::gfp]) strain, we attempted to amplify low-level signals, by inserting Cre recombinase at the C-terminus of the hdl-1 locus (hdl-1(syb4208\\[hdl-1::t2a::3xnls::cre])). We crossed this strain to the recently published \u2018Flexon\u2019 strain (arTi361\\[rps-27p::gfp\"flexon\"-h2b::unc-54\u20133'UTR]) (*Shaffer and Greenwald, 2022*). Even low expression of hdl-1 should have led to Cre-mediated excision of the flexon stop cassette, which is designed to abrogate gene expression by a translational stop and frameshift mutation, and subsequently can", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 602, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "195a7a26-90a9-4412-9678-e129751cf736": {"__data__": {"id_": "195a7a26-90a9-4412-9678-e129751cf736", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.40, para 1](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "898d70cf-fd51-4fe3-939d-ea513b62c0bd", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.40, para 1](https://elifesciences.org/articles/95402)"}, "hash": "fe72cc019061add2691653825eb5207435e4bde442b450c321f1a40b4658c7b2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "result in strong and sustained gfp expression under the control of the rps-27 promoter and thereby providing information about cell-specific hdl-1 expression. However, no robust, consistent reporter expression was seen in hdl-1(syb4208\\[hdl-1::t2a::3xnls::cre]); arTi361\\[rps-27p::gfp\"flexon\"-h2b::unc-54\u20133'UTR] animals.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 320, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f35aea28-e4f3-4b7c-b20b-95046631500a": {"__data__": {"id_": "f35aea28-e4f3-4b7c-b20b-95046631500a", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.40, para 2](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f320c3d8-56b9-4218-8895-438c814c7780", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.40, para 2](https://elifesciences.org/articles/95402)"}, "hash": "4d67e4739d109dc287b2670aeba1fef177f606acf2335a48bec3f7ecc29cff0d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Three of the reporter alleles that we generated were already previously examined in specific cellular contexts:", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 111, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "aecb8706-9644-4724-8c96-ba81780c2e2c": {"__data__": {"id_": "aecb8706-9644-4724-8c96-ba81780c2e2c", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.40, para 3](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a7276034-102c-41fc-9ee7-16336bb2e02f", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.40, para 3](https://elifesciences.org/articles/95402)"}, "hash": "fd3309fc9deac14e74adc296fa9b0a109c841a32b16199d38fff86853a15ba3b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* unc-17(syb4491\\[unc-17::t2a::gfp:h2b]) IV (Vidal et al., 2022)\n* eat-4(syb4257\\[eat-4::t2a::gfp::h2b]) III (Vidal et al., 2022)\n* bas-1(syb5923\\[bas-1::sl2::gfp::h2b]) III (Yu et al., 2023)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 191, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b0612035-facc-447c-9b53-dbda7f095a61": {"__data__": {"id_": "b0612035-facc-447c-9b53-dbda7f095a61", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.40, para 4](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a0a13380-771d-4115-ac72-07d3267eae58", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.40, para 4](https://elifesciences.org/articles/95402)"}, "hash": "813af5fca047c3482891662a7ec7f1da826a526a7b92fe42dc1745a007b130d2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "One of the reporter alleles was obtained from the Caenorhabditis Genetics Center (CGC):", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 87, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "09590c80-fc5c-423a-8626-dd9e25283d0a": {"__data__": {"id_": "09590c80-fc5c-423a-8626-dd9e25283d0a", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.40, para 5](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "661e5f2a-d754-4a1b-815e-f582fe7802ca", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.40, para 5](https://elifesciences.org/articles/95402)"}, "hash": "153c0c32d4c08f2ccf56339ce8f46b6d23bdf42969ab0810cd01987bfb9bf746", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* mod-5(vlc47\\[mod-5::t2a::mNeonGreen]) I (Maicas et al., 2021)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 63, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0bb2c71a-7a9f-44fb-8262-cf5307af6548": {"__data__": {"id_": "0bb2c71a-7a9f-44fb-8262-cf5307af6548", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.40, para 6](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "af144906-e3d6-408e-8b78-1e4cdb24a5cc", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.40, para 6](https://elifesciences.org/articles/95402)"}, "hash": "47fee7d79b4f295abffc0c28b5bbf67ae1706ec146fa8df09d60bdad906acef3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Microscopy and image processing", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 34, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "439aa7f8-367a-4ca1-ae20-3f2238a30c78": {"__data__": {"id_": "439aa7f8-367a-4ca1-ae20-3f2238a30c78", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.40, para 7](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7d0521c9-56ab-48ac-9623-4e93dca66c03", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.40, para 7](https://elifesciences.org/articles/95402)"}, "hash": "6438ef9b515b532ba37df6fe4afede1345e4b50db5e18a09b68a44d17c52d1e8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "For adult animal imaging, 15\u201325 (exact number depending on the difficulty of neuron ID) same-sex L4 worms were grouped on NGM plates 6\u20139 hr prior to imaging to control for accurate staging and avoid mating. Young adult worms were then anesthetized using 50\u2013100 mM sodium azide and mounted on 5% agarose pads on glass slides. Z-stack images were acquired with ZEN software using Zeiss confocal microscopes LSM880 and LSM980 or a Zeiss Axio Imager Z2 and processed with ZEN software or FIJI (Schindelin et al., 2012) to create orthogonal projections. Brightness and contrast, and in some cases gamma values, were adjusted to illustrate dim expression and facilitate neuron identification.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 686, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "59a30826-f08a-499c-ba87-17f720f7c022": {"__data__": {"id_": "59a30826-f08a-499c-ba87-17f720f7c022", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.40, para 8](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f6b4c1b1-cb92-49a4-8d78-f278cfbb3bda", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.40, para 8](https://elifesciences.org/articles/95402)"}, "hash": "a0b1e021cf6256d3c43790534197b3d17d1c5b90e5d84315217996459062c293", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Neuron class and cell-type identification", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 44, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ac476473-89f7-4b3e-a12d-d0d47f96d4f4": {"__data__": {"id_": "ac476473-89f7-4b3e-a12d-d0d47f96d4f4", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.40, para 9](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f5e9c781-d390-4482-9ab8-b4c163239972", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.40, para 9](https://elifesciences.org/articles/95402)"}, "hash": "c0ffb9e56485696e96fcb36704166c1a4d85757f0223ae7d556edb2060597f99", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Neuron classes were identified by crossing the gfp reporter alleles with the landmark strain 'NeuroPAL' (allele otIs669 or otIs696, for bright reporters and dim reporters, respectively) and following published protocols (Tekieli et al., 2021; Yemini et al., 2021) (also see 'lab resources' at hobertlab.org). For neuron identification of the eat-4(syb4257), unc-46(syb7278), and unc-47(syb7566) reporter alleles in hermaphrodites, the reporter alleles were also crossed into the fosmid-based reporter transgenes of the same gene \\[eat-4(otIs518), unc-46(otIs568), and unc-47(otIs564)] as a 'first-pass' to identify potential non-overlapping expression of the two alleles. For tph-1(syb6451) analysis, an eat-4 fosmid-based reporter (otIs518) was also used. For identification of VC4, VC5, HSN, and uv1, an ida-1p::mCherry integrant (LX2478, lin-15(n765ts) X; vsls269\\[ida-1::mCherry]) was also used in some cases (Fernandez et al., 2020). For phasmid neurons, dye-filling with DiD (Thermo Fisher Scientific) was sometimes used to confirm neuron ID. For glial expression, a panglial reporter otIs870\\[mir-228p::3xnls::TagRFP] was used. For hypodermal cells identification, a dpy-7p::mCherry reporter stIs10166 \\[dpy-7p::his-24::mCherry+unc-119(+)] was used (Liu et al., 2009).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1275, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "acbc123c-5892-4276-83c4-7b543446b46b": {"__data__": {"id_": "acbc123c-5892-4276-83c4-7b543446b46b", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.40, para 10](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "607464ca-ffbd-400c-bf28-8dcb835bcd56", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.40, para 10](https://elifesciences.org/articles/95402)"}, "hash": "9312acb5ba575588d152c6c958f41d64e63bbb1ba3796d74fe6f6abc828b83ec", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Resource availability", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 24, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b8516f7a-8541-4a2c-a963-8c7356dd496b": {"__data__": {"id_": "b8516f7a-8541-4a2c-a963-8c7356dd496b", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.40, para 11](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3289aa54-6416-48cf-879e-69cb73985b06", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.40, para 11](https://elifesciences.org/articles/95402)"}, "hash": "2aa486629bfe5051cc9272d85fe06214df5b580162b2d238692ea26abdbeffb2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Lead contact", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 16, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2648bb18-1876-4651-a9b1-5afc5c8bbc26": {"__data__": {"id_": "2648bb18-1876-4651-a9b1-5afc5c8bbc26", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.40, para 13](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b1b4cf2b-3d65-4cd5-89fc-37fe964afa61", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.40, para 13](https://elifesciences.org/articles/95402)"}, "hash": "7fbf179623189c262bcbc7554c506c7f4c04fa0629fff7cd8b6efbd9e4a378f6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ") is the Lead Contact.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 22, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "02c568e3-fed9-431b-979a-eab50711fc7b": {"__data__": {"id_": "02c568e3-fed9-431b-979a-eab50711fc7b", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.40, para 14](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7549fc96-bf87-42e2-94f5-ae2fce43796b", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.40, para 14](https://elifesciences.org/articles/95402)"}, "hash": "b868dd9b3cf6d39bb21f60e24fb67679841ea46342e8c1a0044c735640080eb3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Materials availability", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 26, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cc64277b-faa9-4c5a-a64e-505ef190e81f": {"__data__": {"id_": "cc64277b-faa9-4c5a-a64e-505ef190e81f", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.40, para 15](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3387908f-f126-44ef-9e89-758bca8d4fc9", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.40, para 15](https://elifesciences.org/articles/95402)"}, "hash": "1ef01f677d22791823a2fadddfa2eb2797bccd6d1eabd02601387c1144af98e8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "All newly generated strains are available at the Caenorhabditis Genetics Center (CGC).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 86, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "61326e91-9f10-46be-bbae-f6b49e9f6cc1": {"__data__": {"id_": "61326e91-9f10-46be-bbae-f6b49e9f6cc1", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.40, para 16](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ab92b038-7f78-4743-9ed7-c7877a7aff4a", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.40, para 16](https://elifesciences.org/articles/95402)"}, "hash": "5adc92acceba07d08b43d3b7b2c0ccce2a12340a4dd721a6138d83bdad1ac2c8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Acknowledgements", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 19, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4e41d655-72f0-400c-ba39-0466fc36c412": {"__data__": {"id_": "4e41d655-72f0-400c-ba39-0466fc36c412", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.40, para 17](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a8f536f2-0efb-4f88-bef2-e2e60ef0c469", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.40, para 17](https://elifesciences.org/articles/95402)"}, "hash": "3bdc63a763bbc79e5e716c1bc8e0ebcb2777f13f3ba46ebc11931a39c7580ca5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We thank Chi Chen for generating nematode strains. We thank Emily Bayer, James Rand, Piali Sengupta, and Esther Serrano-Saiz for comments on the manuscript, Frank Schroeder and Marie Gendrel for discussion and communicating unpublished results, Aakanksha Singhvi for discussing glia scRNA data and Michael Koelle for an ida-1 reporter strain. Some strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). This work was funded by the Howard Hughes Medical Institute and by NIH R01 NS039996.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 548, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2f9f6bd9-262f-4839-811e-8bf2a8207fd9": {"__data__": {"id_": "2f9f6bd9-262f-4839-811e-8bf2a8207fd9", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.41, para 1](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1215c089-c9d4-42e3-bce2-608933470d2e", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.41, para 1](https://elifesciences.org/articles/95402)"}, "hash": "a18ec238197e8da06ca7786b7959accbe2b46c3fd7aeb3e3bb137fdcf2fa00e5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Additional information", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 24, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "211c1d3d-d70f-4118-9060-d4216b3f2384": {"__data__": {"id_": "211c1d3d-d70f-4118-9060-d4216b3f2384", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.41, para 2](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c54aa6a7-d922-428d-acb1-875b0e378eeb", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.41, para 2](https://elifesciences.org/articles/95402)"}, "hash": "ea13f11edde1a60614278a67bfe12c4d7c871fd23604097a97bfb71aac693f2e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Funding", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 10, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ab22b4dd-85ff-41fa-a974-a2ed5b1fe38e": {"__data__": {"id_": "ab22b4dd-85ff-41fa-a974-a2ed5b1fe38e", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.41, para 3](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ab45aa2d-30e1-464e-99bd-ef80e244c31a", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.41, para 3](https://elifesciences.org/articles/95402)"}, "hash": "afd2e8e08167ae077efa0ca24f8321e5b2f372c0662a34f88c6b9eea4e8362ce", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Funder|Grant reference number|Author|\n|-|-|-|\n|National Institutes of Health|NS039996|Oliver Hobert|\n|Howard Hughes Medical Institute||Oliver Hobert|\n|National Institutes of Health|Office of Research Infrastructure Programs P40 OD010440|Oliver Hobert|\nThe funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 381, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cd9afc3c-6d83-4c68-ac5d-d117aed66ed4": {"__data__": {"id_": "cd9afc3c-6d83-4c68-ac5d-d117aed66ed4", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.41, para 4](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "50cc300c-0f8f-449b-92fb-920f78333b87", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.41, para 4](https://elifesciences.org/articles/95402)"}, "hash": "d1cb6fe780786fde407071045406adb7dc07ade28b4ddc6ee4dc251d75ed2f31", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Author contributions", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 23, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "135d58a2-f146-4e78-8e77-1d684234aeec": {"__data__": {"id_": "135d58a2-f146-4e78-8e77-1d684234aeec", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.41, para 5](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7bf28781-a8c4-4980-9695-f98cfab5fb80", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.41, para 5](https://elifesciences.org/articles/95402)"}, "hash": "86911c17dc914c14a16a65bfe523173b10092d8f83027834d572f893d23a977a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Chen Wang, Conceptualization, Data curation, Formal analysis, Investigation, Visualization, Writing \u2013 original draft; Berta Vidal, Surojit Sural, Curtis Loer, G Robert Aguilar, Daniel M Merritt, Itai Antoine Toker, Merly C Vogt, Cyril C Cros, Investigation, Visualization, Writing \u2013 review and editing; Oliver Hobert, Conceptualization, Supervision, Funding acquisition, Writing \u2013 original draft, Project administration", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 419, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6bdae1ff-2aac-42ac-b6cf-5031b10c862d": {"__data__": {"id_": "6bdae1ff-2aac-42ac-b6cf-5031b10c862d", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.41, para 6](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a909cab4-7b29-439c-9459-208fc7a8cb6d", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.41, para 6](https://elifesciences.org/articles/95402)"}, "hash": "62787a2ff4e11b56cbcaba457c66093bf6b62cdc43869ba2f983a9b7006d87ae", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Author ORCIDs", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 16, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7185e86a-faed-4257-a53f-fa76427e8e2f": {"__data__": {"id_": "7185e86a-faed-4257-a53f-fa76427e8e2f", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.41, para 7](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8f598e0f-4c03-4d1d-97f8-96047e0b4930", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.41, para 7](https://elifesciences.org/articles/95402)"}, "hash": "3c3fa62fdf21c0bd628ed7102d0f8c7f3ccfda397d86a6b031c27dd0e12d83fa", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* Chen Wang \n* Surojit Sural \n* G Robert Aguilar \n* Itai Antoine Toker \n* Cyril C Cros \n* Oliver Hobert", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 103, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "446ed02f-7167-4b31-bc0e-263ae7532fb1": {"__data__": {"id_": "446ed02f-7167-4b31-bc0e-263ae7532fb1", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.41, para 8](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4c30eaef-29c4-4805-8ac6-306cfab1f82b", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.41, para 8](https://elifesciences.org/articles/95402)"}, "hash": "628b1c5e2ff9f4cc269093d6af0de02ee630b24df1ebaf696beea926d585f804", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Peer review material", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 23, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4aeeb4f1-8dd7-4be4-b9dd-dad357ef5b34": {"__data__": {"id_": "4aeeb4f1-8dd7-4be4-b9dd-dad357ef5b34", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.41, para 9](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "84cf61af-1ca3-434b-8011-a8a2340f4961", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.41, para 9](https://elifesciences.org/articles/95402)"}, "hash": "4544b1c00388b500543226e0705c9bed564cb42b0fa83018a9ab43fa029e65ff", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* Reviewer #1 (Public review): \n* Reviewer #2 (Public review): \n* Reviewer #3 (Public review): \n* Author response", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 113, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e58e52a2-9f3a-4358-9da9-408e32bd56e4": {"__data__": {"id_": "e58e52a2-9f3a-4358-9da9-408e32bd56e4", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.41, para 10](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7bd6596e-c113-4adf-9804-a6a977f05be9", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.41, para 10](https://elifesciences.org/articles/95402)"}, "hash": "d6d3400e7fd7203204f68d318ecadad07f335769ec96d90b4cc1a052ec106c23", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Additional files", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 19, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1b0f4e1f-bed4-49dc-9ce4-18cb0a77e1cb": {"__data__": {"id_": "1b0f4e1f-bed4-49dc-9ce4-18cb0a77e1cb", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.41, para 11](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "dcaaf47e-14af-424c-a9c1-0c747006171f", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.41, para 11](https://elifesciences.org/articles/95402)"}, "hash": "52d2c73d6ccc9a2aef2d8883d052673d0ad841f6f431339948077bd77c94123c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Supplementary files", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 23, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "385839ce-5482-4cf3-82ce-123269875b55": {"__data__": {"id_": "385839ce-5482-4cf3-82ce-123269875b55", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.41, para 12](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "78deeaa7-020d-4a45-b8ea-534c164f77c6", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.41, para 12](https://elifesciences.org/articles/95402)"}, "hash": "06d8138d0111c74e1795f2957bd7fbf486a58b93b4a7818ccb7ec3fbf81bdcc0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* Supplementary file 1. Single-cell RNA (scRNA) data for neurotransmitters in the hermaphrodite. Here, we show expression of previous reporters and reporter alleles used in this study, compared to scRNA data. Note that scRNA expression values for *eat-4* and *unc-47* can be unreliable because they were overexpressed to isolate individual neurons for scRNA analysis (*Taylor et al., 2021*).\n* Supplementary file 2. Updated expression patterns of neurotransmitter pathway genes in hermaphrodites.\n* Supplementary file 3. Updated expression patterns of neurotransmitter pathway genes in male-specific neurons.\n* Supplementary file 4. Summary of sexually dimorphic use of neurotransmitter pathway genes in sex-shared neurons.\n* Supplementary file 5. Summary of updates to expression patterns of classic neurotransmitter pathway genes.\n* MDAR checklist", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 849, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "bf0ba5d1-1ee7-469f-aa95-71f46e6dc0ec": {"__data__": {"id_": "bf0ba5d1-1ee7-469f-aa95-71f46e6dc0ec", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.41, para 13](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "90c8bc54-47d6-40a5-a58d-291db108d9c1", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.41, para 13](https://elifesciences.org/articles/95402)"}, "hash": "95aa92a64753e2ccf5403b667aaf311a9867aaa84745e3f5480b5f1591ecf549", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Data availability", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 21, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1e4925b0-01d5-4068-ad06-7fdf8d48bd18": {"__data__": {"id_": "1e4925b0-01d5-4068-ad06-7fdf8d48bd18", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.41, para 14](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "38304449-993c-421d-bcae-f68a753d4521", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.41, para 14](https://elifesciences.org/articles/95402)"}, "hash": "27640ca11bb5a51997c661b2c52112a4872a6340c001da5671125b13cd903bc5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "All data generated or analysed during this study are included in the manuscript and supporting files.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 101, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c31ef813-4626-420a-9e64-cc8877239aa8": {"__data__": {"id_": "c31ef813-4626-420a-9e64-cc8877239aa8", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.42, para 0](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "78765d05-9778-46c4-a6cc-c961fd026b31", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.42, para 0](https://elifesciences.org/articles/95402)"}, "hash": "d0d1920d2c466e6d2613f68b34e33d750a3c9661662382b83e826d882233c271", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# References", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 12, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "bf634d98-9c24-4de8-b42c-84e635e56207": {"__data__": {"id_": "bf634d98-9c24-4de8-b42c-84e635e56207", "embedding": null, "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.42, para 1](https://elifesciences.org/articles/95402)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9fb37919-76d7-4434-8525-21c13dc5ae5c", "node_type": "4", "metadata": {"source document": "Publication: [Wang2024_NeurotransmitterAtlas, p.42, para 1](https://elifesciences.org/articles/95402)"}, "hash": "0083bb73335aae7f106775b81a2e88fb091e5793d5b617f0013507475a552d6b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Alfonso A, Grundahl K, McManus JR, Asbury JM, Rand JB. 1994. 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DOI: , PMID: 26536134", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 809, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "73f48d63-47be-4d5a-a669-d30055e44849": {"__data__": {"id_": "73f48d63-47be-4d5a-a669-d30055e44849", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.1, para 0](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "22021490-3c38-4352-9874-92492835ae9d", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.1, para 0](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "2938160ed8c4b7f6beba2af56fb62471a6b1049606f29fd87d8652097d68813a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "frontiers in COMPUTATIONAL NEUROSCIENCE\nORIGINAL RESEARCH ARTICLE\npublished: 07 March 2012\ndoi: 10.3389/fncom.2012.00010", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 120, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "15b3858e-58bf-41ab-a914-90e03091bdca": {"__data__": {"id_": "15b3858e-58bf-41ab-a914-90e03091bdca", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.1, para 1](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1aaba386-a6f8-459c-9536-7bc21fd11c5f", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.1, para 1](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "ae45c8003d109138fd79e9bcf78cdda871a30cd72119d0ef3e1749638b5e118b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Gait modulation in *C. elegans*: an integrated neuromechanical model", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 70, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8ecb64b9-02d7-4355-b17a-c8c1172e7bce": {"__data__": {"id_": "8ecb64b9-02d7-4355-b17a-c8c1172e7bce", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.1, para 2](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3f493acf-06b5-4b9b-ba37-b1d9752112bb", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.1, para 2](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "9705aadf8dbb3913d11b904a83190b116895b5f0273e5f5c68d595e4ab2812e8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Jordan H. Boyle^1\u2020, Stefano Berri^1\u2020 and Netta Cohen^1,2**\\*", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 62, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "454ff8c3-125b-414a-a764-56abaff94f61": {"__data__": {"id_": "454ff8c3-125b-414a-a764-56abaff94f61", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.1, para 3](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8f50859f-4f0a-473a-beee-7f2bddf1dee0", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.1, para 3](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "4480b428302391a8c8d19d3a6725989a66488bdb91a22d80821a4cbc04e1ec56", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "^1 School of Computing, University of Leeds, Leeds, UK ^2 Institute of Membrane and Systems Biology, University of Leeds, Leeds, UK", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 131, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d68ede87-c9f1-4730-a1e8-59b6501d009d": {"__data__": {"id_": "d68ede87-c9f1-4730-a1e8-59b6501d009d", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.1, para 4](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fb536a62-a646-45ae-a29c-78f11c4fa78b", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.1, para 4](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "edb0f5592e9ee9aaff42d3b5ac526d0763f1da91ec7c18a1a0050b4619af6bf5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Edited by:**\nMisha Tsodyks, Weizmann Institute of Science, Israel", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 67, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cc387465-c881-49b5-821c-0d3f23f38fad": {"__data__": {"id_": "cc387465-c881-49b5-821c-0d3f23f38fad", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.1, para 5](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ac0c0879-f35c-40d8-82d0-05f6749dfa12", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.1, para 5](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "4fa5f854f575642dd734f8e04dfa03c2332cc5e155ad27398190d97281335110", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Reviewed by:**\nMisha Tsodyks, Weizmann Institute of Science, Israel\nAlexander G. Dimitrov, Washington State University Vancouver, USA", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 135, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8afa47ec-619c-40ff-a79d-75a52c505453": {"__data__": {"id_": "8afa47ec-619c-40ff-a79d-75a52c505453", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.1, para 6](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ce060bd9-a6e0-4727-bcae-d2f7de0911b2", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.1, para 6](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "79d6f78b5fe9278733777ae16ac73b8e255af41ee26b4016f33c474caafb2385", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "\\***Correspondence:**\nNetta Cohen, School of Computing, University of Leeds, Leeds LS2 9JT, UK.\ne-mail:", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 103, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2ef773f8-86f8-4754-9dc7-d11899990561": {"__data__": {"id_": "2ef773f8-86f8-4754-9dc7-d11899990561", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.1, para 7](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3cc9d7ad-81e9-460d-8bcf-ae84e056919e", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.1, para 7](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "4aa485582fa7aed02e07fb3351999714c327264300ae8960486447446840aa08", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "^\u2020**Present address:**\nJordan H. Boyle, School of Mechanical Engineering, University of Leeds, Leeds, UK;\nStefano Berri, Leeds Institute of Molecular Medicine, St James\u2019s University Hospital, Leeds, UK.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 202, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e413f982-3829-4b6d-8f1e-420ca7237fa6": {"__data__": {"id_": "e413f982-3829-4b6d-8f1e-420ca7237fa6", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.1, para 8](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3485b130-90f9-4098-a181-ac4f5530a375", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.1, para 8](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "23110fc24897049640cbbcb7f445f364b5e9bcbaa0f10d2d3be28e2ae7ff3554", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Equipped with its 302-cell nervous system, the nematode *Caenorhabditis elegans* adapts its locomotion in different environments, exhibiting so-called *swimming* in liquids and *crawling* on dense gels. Recent experiments have demonstrated that the worm displays the full range of intermediate behaviors when placed in intermediate environments. The continuous nature of this transition strongly suggests that these behaviors all stem from modulation of a single underlying mechanism. We present a model of *C. elegans* forward locomotion that includes a neuromuscular control system that relies on a sensory feedback mechanism to generate undulations and is integrated with a physical model of the body and environment. We find that the model reproduces the entire swim-crawl transition, as well as locomotion in complex and heterogeneous environments. This is achieved with no modulatory mechanism, except via the proprioceptive response to the physical environment. Manipulations of the model are used to dissect the proposed pattern generation mechanism and its modulation. The model suggests a possible role for GABAergic D-class neurons in forward locomotion and makes a number of experimental predictions, in particular with respect to non-linearities in the model and to symmetry breaking between the neuromuscular systems on the ventral and dorsal sides of the body.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1375, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2d3715c3-17f5-4667-894a-9476438f694a": {"__data__": {"id_": "2d3715c3-17f5-4667-894a-9476438f694a", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.1, para 9](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "97403ce9-d135-4d16-8a2d-2c3c7bd8201f", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.1, para 9](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "9dc68bfdbcf4dd600083c7f603ccd52b16b6715e6e8e76b01db6e73aa7c0096f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Keywords: invertebrate, locomotion, motor control, neuromechanical model, proprioception**", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 92, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "386f795b-277f-4482-b22c-84b8118c3667": {"__data__": {"id_": "386f795b-277f-4482-b22c-84b8118c3667", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.1, para 10](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4fca57f3-a986-4ea7-8e28-ca7ea3e1de29", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.1, para 10](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "79f6a993e0a6428fd1f0f4fe49e5455a3d0e368b7381a5b9f324a8e575915a8c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## 1. INTRODUCTION", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 18, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cbd72a85-961c-4e4f-b816-2a5c607f4f08": {"__data__": {"id_": "cbd72a85-961c-4e4f-b816-2a5c607f4f08", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.1, para 11](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a1a3286c-e6a5-40ff-ad2d-8b99c8070bbf", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.1, para 11](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "bf3956623ff6b7e81c589b5f93c717b1941ba7e3b8f0c30fd04d607c0f071e1a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "One essential requirement for the survival of most animals is the ability to move around in a world characterized by complex, unpredictable, and variable environments. Adapting to different environments often involves the use of qualitatively distinct patterns of locomotion, called gaits. The animal\u2019s nervous system is responsible for generating the rhythmic neuromuscular activity associated with each of these gaits and must coordinate the task of switching seamlessly between them. Furthermore, the animal must be able to reliably adapt any of these patterns in response to external perturbations. Understanding the neural basis of animal locomotion is an important challenge that has received considerable attention (Kiehn et al., 1998; Grillner and Wall\u00e9n, 2002; Hill et al., 2003; Borgmann et al., 2009).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 812, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "98b4bf70-fe10-4305-ba58-edc2bc76f37f": {"__data__": {"id_": "98b4bf70-fe10-4305-ba58-edc2bc76f37f", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.1, para 12](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2e649386-6784-4f33-9572-32486ec150b7", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.1, para 12](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "ea2e422a981bcd33287d8634dda81dfe3fcf4f25933d548cb93d98e9dcd52738", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The popular model organism *Caenorhabditis elegans* is a tiny (\\approx1 mm long) nematode worm with a largely invariant nervous system, consisting of exactly 302 neurons with known connectivity (White et al., 1986; Chen et al., 2006). Moreover, the behavioral roles of many of these neurons have been uncovered using experimental techniques including targeted cell killing (Chalfie et al., 1985; McIntire et al., 1993b) and genetic mutations (Brenner, 1974; McIntire et al., 1993a). The result is an organism in which the nervous system is mapped at cellular resolution. Despite its small size and the apparent simplicity of the underlying nervous system, the worm is capable of a surprisingly rich repertoire of behaviors including navigation and foraging, mating, learning, and even rudimentary social behavior (aggregation).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 827, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3072566f-f34e-42bb-8c73-4acfbf92acd9": {"__data__": {"id_": "3072566f-f34e-42bb-8c73-4acfbf92acd9", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.1, para 13](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d80df15e-8316-455f-98b6-5d452986fc56", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.1, para 13](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "a29193881f142c6c72a809d8fedeb1939e457b7543b41e003a35d740ea12aed1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Central to all of these behaviors, the worm\u2019s locomotion is remarkably adaptive and changes in response to its environment. Specifically, the body undulations used by the worm when swimming in liquid or crawling on a firm gel substrate like agar are kinematically different (see Movie S1 in Supplementary Material), and have generally been thought to represent two distinct gaits (White et al., 1986; Pierce-Shimomura et al., 2008). In line with this two gait hypothesis, previous models of the worm\u2019s locomotion (Niebur and Erd\u00f6s, 1991; Bryden and Cohen, 2004, 2008; Karbowski et al., 2008) have mostly addressed crawling on agar. Recent results, however, demonstrated that forward swimming and crawling are two extremes in a spectrum of behaviors. Indeed the intermediate waveforms can be revealed by placing worms in appropriate intermediate media (Berri et al., 2009; Fang-Yen et al., 2010; Sznitman et al., 2010; Boyle et al., 2011). The continuity of the swim-crawl transition strongly suggests that the entire range of behaviors are produced through modulation of a single neural mechanism. This discovery sets an exciting new challenge to develop a model of the worm that is capable of reproducing the entire range of locomotor behaviors.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1246, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b380ecee-6375-4555-a4cd-889d6a2eddfc": {"__data__": {"id_": "b380ecee-6375-4555-a4cd-889d6a2eddfc", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.1, para 14](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "56f8943a-d10b-40ba-baad-93eb5bbf20cf", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.1, para 14](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "55a025d8feb25c7a0b136b14227603972561a4a48e85e020fcfffab256f330e7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Here we present an integrated neuromechanical model of *C. elegans* forward locomotion, grounded in the neurobiology, anatomy, and physics of the real worm, that successfully accounts for locomotion across a range of media from water to agar, as well as in more complex inhomogeneous environments. This model suggests that sensory feedback mechanisms are sufficient to account for the observed modulation of the locomotion behavior in", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 434, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "76e17520-8307-4806-8d88-195e2fc0f59c": {"__data__": {"id_": "76e17520-8307-4806-8d88-195e2fc0f59c", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.1, para 15](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "30d414c5-e270-4610-abe8-6db59630f632", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.1, para 15](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "f536188ebd777828f4619aec5f083c6a865a13260e1561d22b246ad958e4b6c2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Frontiers in Computational Neuroscience | www.frontiersin.org | March 2012 | Volume 6 | Article 10 | **1**", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 106, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7e277c30-413c-4696-ad51-d53a69053c21": {"__data__": {"id_": "7e277c30-413c-4696-ad51-d53a69053c21", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.2, para 0](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "49cae902-fde9-4855-ba0c-fd32b3011dfb", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.2, para 0](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "82aea9e66e5f120e1085961e8347305aaa0e33be33efbe1449bd926a7b615488", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Boyle et al. Neuromechanical model of *C. elegans* locomotion", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 61, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6f6ce3c4-44e3-4e94-85dc-1621c766ed06": {"__data__": {"id_": "6f6ce3c4-44e3-4e94-85dc-1621c766ed06", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.2, para 1](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ca454120-d409-4003-8d8c-e4c616bff426", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.2, para 1](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "8e4bacac1ba6d8c88be398161861c40db3fe6ac6b47990384a02ad37a943e08c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "different environments. Analysis of the model sheds further light on the mechanisms that generate and modulate the oscillations and leads to a number of experimental predictions.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 178, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b1e68648-35a8-4b90-acfb-bf93fef89e3f": {"__data__": {"id_": "b1e68648-35a8-4b90-acfb-bf93fef89e3f", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.2, para 2](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ef267d67-56cd-4199-a2a7-ef0fd6c9c438", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.2, para 2](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "18199e337c7b77bf3d77f8118309a31d14ba33ba502f77d3045bd9e0b9ebe21b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# 2. MATERIALS AND METHODS", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 26, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0a2a31cb-881e-481b-9eb8-6e495e5671e8": {"__data__": {"id_": "0a2a31cb-881e-481b-9eb8-6e495e5671e8", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.2, para 3](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6441e9de-49a2-46fa-9daf-67c94a43ec8e", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.2, para 3](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "375cbd1162fe734fc8f8ba1edd53ae9e97d49d7a7aaa195ac332ffd8d6d7ae25", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We begin with the premise, grounded in the *C. elegans* circuitry that a single neural circuit is responsible for all of the worm's forward locomotion, from slow (0.5 Hz), short wavelength, sinuous crawling patterns to fast (2 Hz), long wavelength, thrashing, or swimming patterns. With this in mind, we set out to develop a model of this neural circuit and its modulation that can account for the entire range of behaviors.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 424, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f7270611-b6b8-46c6-94a0-1a56732e6720": {"__data__": {"id_": "f7270611-b6b8-46c6-94a0-1a56732e6720", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.2, para 4](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7c070c8e-9023-4d7b-a053-8404e267bb52", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.2, para 4](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "491b10d25d105e21ec9b7d25138a2f7f2f849256564267ddc267a995cdb4372b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "A large body of previous work (Niebur and Erd\u00f6s, 1991; Sauvage, 2007; Berri et al., 2009; Boyle, 2010; Fang-Yen et al., 2010; Sznitman et al., 2010; Petzold et al., 2011; Shen and Arratia, 2011) has found that the physics of the worm's body and environment are important components of the locomotion system. In particular, any model that is meant to account for motor behavior across different physical environments must incorporate the corresponding physics in some manner. In our model, as explained below, it is also important to capture the detailed shape of the body, as it may impact on any proprioceptive feedback mechanisms.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 632, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "35d25fe2-9df5-4cbf-b081-968669461364": {"__data__": {"id_": "35d25fe2-9df5-4cbf-b081-968669461364", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.2, para 5](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "15f34505-66ed-449c-9a59-18df714b771b", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.2, para 5](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "6ffa9b087cc8a5fd85e3646739f4cafaeede15b42387437f65a39e532aaebfa5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Stretch-receptor-mediated proprioception has long been postulated to exist in *C. elegans* motoneurons and has recently been reported experimentally (Li et al., 2006; Schafer, 2006). Specifically, proprioceptive mechanisms are thought to channel information to the motoneurons about the bending of the body (posteriorly and possibly locally). In differing physical environments, the response to identical muscle activation patterns would produce different body shapes, thus constituting completely passive environment-mediated modulation of the locomotion. Under such conditions, one would also expect the proprioceptive signal to differ, providing closed-loop neural control and adaptation of the neuromuscular pattern of activity to variable environments. Indeed, in our model, such sensory feedback is the primary driving force behind the oscillation mechanism.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 864, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3b784d41-c9fc-4645-ba9f-884d62c33296": {"__data__": {"id_": "3b784d41-c9fc-4645-ba9f-884d62c33296", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.2, para 6](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a20469a9-76b4-41d2-b6f1-a2474c79dae3", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.2, para 6](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "c65af10c804e87803e9fb1e505e26245eaf2d41aa5c0383b6d9d98545b0146ba", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The model description that follows is consistent with the order in which the model was developed and parameters fixed. Specifically, the physical parameters of the environment should be independent from the choice of model of the worm, and so were fixed first. Following similar logic, the behavior of the passive body (lacking neuromuscular control) was modeled second and all corresponding parameters were fixed. The muscles were modeled next, and the neural control was incorporated last, without any modifications to already set parameters of the muscles, body, or environment. The model software is available as supporting information (S14).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 646, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1c9a0bf3-e2d3-4879-9f45-886a576b4f6a": {"__data__": {"id_": "1c9a0bf3-e2d3-4879-9f45-886a576b4f6a", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.2, para 7](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "78434419-f594-4bb4-a4b3-7e1c4e9da8d3", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.2, para 7](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "5f7402b414a274c640cd7cd10e6bc2c6ac621c7a3ca23bca8a6d2ade2eff9775", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## 2.1. PROPERTIES OF THE ENVIRONMENT", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 37, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "50a8a72b-d4a4-4358-9639-822d7ea8d472": {"__data__": {"id_": "50a8a72b-d4a4-4358-9639-822d7ea8d472", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.2, para 8](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "877f4c10-0ec8-4a30-bc7b-8016ccf8bf98", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.2, para 8](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "549ca0112e6fc804c497003fb80dfe904db2c4212ef56e661fe8a1a743acee80", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Small size and relatively slow speeds mean that the worm's motion is well described by low Reynolds number physics, in which inertial forces can be neglected. As previously demonstrated (Berri et al., 2009), the resistive forces applied by the worm's physical environment can be well represented by local drag coefficients resisting motion tangential (C\\_||) and normal (C\\_\\perp) to the local body surface. In Newtonian fluids of known viscosity, values of drag coefficients can be determined from slender body theory, using equations due to Lighthill (1976)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 559, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "db48fe7c-c045-4f45-b2e4-209703889b8b": {"__data__": {"id_": "db48fe7c-c045-4f45-b2e4-209703889b8b", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.2, para 9](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c4638cd5-c1e9-4ad2-ab59-a2f4fbe463cf", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.2, para 9](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "c0cc6803fe5ad298ec5ba2e396347451fa94957ab6347ce04e420bd7c9a296dd", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "C\\_||,  water = L \\frac{2\\pi\\mu}{\\ln(2q/a)} (1)\nC\\_\\perp,  water = L \\frac{4\\pi\\mu}{\\ln(2q/a) + 0.5},", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 101, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "56195491-31fc-413a-ab9f-d413cb80b896": {"__data__": {"id_": "56195491-31fc-413a-ab9f-d413cb80b896", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.2, para 10](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7d0715a6-240c-4914-9d3f-09e3424ba8fc", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.2, para 10](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "11db76a5bcde2d3a18bad5cf1895579d0aeaefbcd6a3abea9cb17541be3ee3c8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "where \\mu is the dynamic viscosity (\\approx 1 MPa\u00b7s for water); q is proportional to the wavelength (\\lambda) of the body wave (typically about 1.5 mm in water, giving q = 0.09\\lambda = 1.35 \\times 10^-4 m); and L = 1 mm and a = 40 \\mum are the length and radius of the body, respectively.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 289, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6eee3561-60c0-4052-95d5-de21e2d68df6": {"__data__": {"id_": "6eee3561-60c0-4052-95d5-de21e2d68df6", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.2, para 11](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a1c21122-c61e-45f9-a74a-fa350201715b", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.2, para 11](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "a0355e144857f7e8a7955b728dfd7fef8e539b12ddd7c2edbe6c1161a3717d51", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Note that the values above are for the whole worm, so the drag coefficient experienced locally along the worm is proportionately smaller. Importantly, in Newtonian environments, the ratio of drag coefficients is fully specified by the geometry of the object, and for the worm is roughly K = C\\_\\perp/C\\_|| \\approx 1.5.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 318, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "97ee2a7b-41ed-43b0-8727-6aa72db72649": {"__data__": {"id_": "97ee2a7b-41ed-43b0-8727-6aa72db72649", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.2, para 12](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0e5c1fed-77c5-4826-844f-11cd42178e99", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.2, para 12](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "9c5d93f9b785c1bcfc6f4a920300dc8e7975bf64350b9109493e63d77cbdf899", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "For agar, Wallace estimated the tangential drag coefficients C\\_||, agar by directly measuring the force required to pull glass fibers of similar dimension to *C. elegans* across the surface (Wallace, 1969). Based on this measurement, Niebur and Erd\u00f6s (1991) estimated C\\_||, agar = 3.2 \\times 10^-3 kg\u00b7s^-1. We previously estimated the normal drag coefficient C\\_\\perp, agar from recordings of wild type worms using our motion simulator (Berri et al., 2009). Briefly, we found the ratio of drag coefficients to be in the range K\\_agar \\approx 30--40; taking a value of K\\_agar = 40 and Niebur and Erd\u00f6s' estimate for C\\_||, agar gives C\\_\\perp, agar = 128 \\times 10^-3 kg\u00b7s^-1, which will be used in what follows.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 714, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b8881183-b26c-40b4-9d08-f8586d5e5d50": {"__data__": {"id_": "b8881183-b26c-40b4-9d08-f8586d5e5d50", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.2, para 13](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7280814b-f476-4252-b245-f776a9d7d900", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.2, para 13](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "db3371e671504af22d1d1a3a7408326e41278b9bab536903ec6ae42567162358", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "For generality in our simulations, we allow all combinations of drag coefficients C\\_|| and C\\_\\perp, such that (i) the minimum drag coefficients correspond to a water environment; (ii) the maximum drag coefficients correspond to estimates of agar properties; and (iii) the ratio of drag coefficients falls within the range 1.5 \\leq K \\leq 40. The specific combinations used are shown in **Figure 4C**.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 402, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "46425244-8757-43c6-9112-dc96fe28c1e4": {"__data__": {"id_": "46425244-8757-43c6-9112-dc96fe28c1e4", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.2, para 14](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a676ea6c-6aa6-4764-9e30-56dd6a177c18", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.2, para 14](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "1fff1cf1c2615f98aa5c82fc2423a695aa4d53f1c07b49acee851fdb3919e99b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## 2.2. THE PHYSICAL MODEL", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 26, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7d919b2b-1227-4009-9329-558a225f82ff": {"__data__": {"id_": "7d919b2b-1227-4009-9329-558a225f82ff", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.2, para 15](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6188923f-4c7a-4fa6-9aee-9e17d1c09778", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.2, para 15](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "ea53ee7e183eb323f6d25e78caf2aa28c6b7573e8ceaa8d41e6d9c5958f3ebe3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In line with previous work (Niebur and Erd\u00f6s, 1991; Boyle et al., 2008), we model the worm's body as a 2D outline. The 2D representation is justifiable as the *C. elegans* body (with the exception of the head) only bends in the dorso-ventral plane. The passive body is modeled as a lightly damped elastic beam. The model body is divided into repeating \"segments\" and articulated by pairs of (D)orsal and (V)entral muscles, with each muscle located in the gap between two points of the physical model (see **Figures 1A,B**). The hydrostatic skeleton and muscles are represented by a combination of damped springs and solid rods connecting these points. Each resulting set of four points and two muscles is referred to as a segment. The number of segments thus corresponds to the number of muscle pairs in the model. We have chosen M = 48 to provide a good approximation of a smooth (biologically unsegmented) body without being excessively computationally expensive. This number also approximates closely the number of muscles along the body (*C. elegans* has 48 dorsal and 47 ventral muscle cells). Note, however, that the term \"segments\" is used for convenience to denote repeating structures, and does not imply biological segmentation. The muscles are modeled as damped", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1272, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "eb3b14ea-8944-41d9-aa8a-8432d6d63ac2": {"__data__": {"id_": "eb3b14ea-8944-41d9-aa8a-8432d6d63ac2", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.2, para 16](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "56086218-d0e8-4c8c-88af-df46e552f163", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.2, para 16](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "11cafa52f48858df5793a7cef7470970c4573e8ee3a4b82ef9dcf2c2a9a60125", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Frontiers in Computational Neuroscience | www.frontiersin.org | March 2012 | Volume 6 | Article 10 | **2**", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 106, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f8227803-67d6-4714-aca9-376a7783308d": {"__data__": {"id_": "f8227803-67d6-4714-aca9-376a7783308d", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 0](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4e585ff8-c06d-4285-a440-587ddf0cb5d7", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 0](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "0f858ff6978ffcdbb3cdd6f9b5e112d049a68d0616dda8544f68c70275bf4efb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Boyle et al. Neuromechanical model of *C. elegans* locomotion", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 61, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "be78a19e-87de-4068-a9fe-420dcd104262": {"__data__": {"id_": "be78a19e-87de-4068-a9fe-420dcd104262", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 1](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "660e8ab7-1cfe-4285-90e5-4a7496bd5cc5", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 1](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "66badd03a869361d6d994f569ec0ec71eb6538565c4d0860c0c4337ff690f290", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "!\\[A diagram showing the physical structure of the worm model with rods, lateral, and diagonal elements. B diagram showing a single segment with nomenclature for points and lengths. C schematic of the neuromuscular circuit with neurons and muscles.]", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 249, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a28e3962-c064-47c1-a265-465d5a294555": {"__data__": {"id_": "a28e3962-c064-47c1-a265-465d5a294555", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 2](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "165d539e-7b23-40b6-a3fe-79070de7f64f", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 2](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "0d1b9ac47c28e8369c0cbb4eb87a9e03365f69f2b3195fd4fc4a4a9acea2a8f5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**FIGURE 1 | (A)** Structure of the physical model. The worm is represented by 49 solid rods (black lines) whose end points (filled black circles) are connected by lateral (red) and diagonal (blue) elements. **(B)** Detailed schematic diagram of a single segment of the physical model illustrating nomenclature. Solid rods maintain equal width, diagonal elements (blue) preserve internal pressure and active muscles line the lateral elements (red). k and \\bar{k} denote opposite ventral and dorsal sides, or vice versa. **(C)** Schematic of the neuromuscular model, showing one of 12 repeating units making up a symmetrized circuit for forward locomotion control. The circuit includes a pair of B-class excitatory neurons (circles), a pair of D-class inhibitory neurons (squares), and four muscles (diamonds) on each side (dorsal and ventral). Synapses are labeled either as excitatory (arrowhead) or inhibitory (circlehead). Posteriorly directed lines from B-class neurons denote the stretch receptor inputs. AVB also forms gap junctional connections with VB and DB (not shown).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1079, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "244e06df-aba2-4851-9fae-3df3240493ab": {"__data__": {"id_": "244e06df-aba2-4851-9fae-3df3240493ab", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 3](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0f719cff-2705-4908-a57c-1de9ba45dd3b", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 3](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "977c1d09277828d62ff69b07b5758b35b318ae70756b3f81725e835afe47e586", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "opposite side to k, i.e., D = \\bar{V} and \\bar{D} = V). *Lateral elements* representing passive cuticle forces and active muscle forces connect each point p*i^k to adjacent points p*{i \\pm 1}^k. The volume-preserving effect of internal pressure is approximated by *diagonal elements* that connect p*i^k to p*{i \\pm 1}^\\bar{k}. Together, these elements yield a net force f\\_i^k on each point. The forces acting on p\\_i^k and p\\_i^\\bar{k} combine into a net force and torque acting on the midpoint of the ith rod.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 511, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "baefd9eb-fba1-49e0-bc1b-8f0a14436f31": {"__data__": {"id_": "baefd9eb-fba1-49e0-bc1b-8f0a14436f31", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 4](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bf3c7ba8-fd41-4095-a53d-94e6433dd84e", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 4](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "aa0184c253abe820e9798d064cfb6345b1438bcbb15b7c3059a091085fe92fef", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Passive body forces", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 23, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7073f6ea-d5ce-4555-9b10-81d87f706004": {"__data__": {"id_": "7073f6ea-d5ce-4555-9b10-81d87f706004", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 5](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8ee58129-db4c-4223-a6e9-2694ccc89b50", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 5](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "88f5f7e7562933d5f1d36e8cb6957854d192bb4a683bbcd9abe60f83b02fd1ff", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In the absence of muscle activation, passive body forces capture the combined effect of the cuticle and internal pressure. In the interest of numerical stability, diagonal elements that strongly resist compression are used to represent the effect of pressure.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 259, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f698e098-957b-4f9c-8e69-a61b873d6df2": {"__data__": {"id_": "f698e098-957b-4f9c-8e69-a61b873d6df2", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 6](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "070df9d7-70f1-492c-859f-aa643e7dc589", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 6](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "c49f2a944354d57470f3a32f342c7d1c3d09d172acb069f5bcf9b3c3256254b3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "For the model to work in a highly resistive environment such as agar, spring forces suffice (Niebur and Erd\u00f6s, 1991; Boyle et al., 2008). However, to model motion in liquid, damping terms must also be included. We therefore model each lateral and diagonal element as a spring in parallel with a damper. Forces applied by the passive lateral elements are given by", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 362, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "58204964-acb5-4df7-baa6-167cefafe9b2": {"__data__": {"id_": "58204964-acb5-4df7-baa6-167cefafe9b2", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 7](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3a577b5a-ddfe-4d56-9ddc-0df1db42b5cb", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 7](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "150908d11a15b9c53136311b62663dd1d4f1053380c962f1035b7665d679a19b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "f\\_L,m^k = \\begin{cases} \\kappa\\_L (L\\_0L,m - L\\_L,m^k) + \\beta\\_L v\\_L,m^k & , \\quad L\\_L,m^k < L\\_0L,m \\ \\kappa\\_L \\[(L\\_0L,m - L\\_L,m^k) \\ \\quad + 2(L\\_0L,m - L\\_L,m^k)^4] + \\beta\\_L v\\_L,m^k & , \\quad otherwise , \\end{cases} \\quad (3)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 238, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5a0e1666-0c1c-40cd-bebf-3d19255040f2": {"__data__": {"id_": "5a0e1666-0c1c-40cd-bebf-3d19255040f2", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 8](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8385bde1-b9db-4c60-a3a7-02074833dd3e", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 8](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "977c414c1dfaaebe590907186faf46c135b0a6b871721e7e3e0e21cc58516776", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "where \\kappa\\_L, \\beta\\_L, and L\\_0L,m denote the lateral spring constant, damping constant, and rest length, respectively. The length of lateral element is L\\_L,m^k while v\\_L,m^k = \\frac{d}{dt} L\\_L,m^k. Note that, due to the non-constant radius, the rest lengths vary along the worm according to L\\_0L,m = \\sqrt{L\\_seg^2 + (R\\_m - R\\_m+1)^2}. Similarly, the forces exerted by diagonal elements are given by", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 409, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2355b391-7c5f-4c9e-a68a-96166ae9501e": {"__data__": {"id_": "2355b391-7c5f-4c9e-a68a-96166ae9501e", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 9](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f28058b6-84cf-43ee-9a8f-c50feac53e17", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 9](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "ba7d6d155ba47006c7a4e8a5671b4cd8bfd462d1abb7d79429737afc6291079b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "f\\_D,m^k = \\kappa\\_D  L\\_0D,m - L\\_D,m^k  + \\beta\\_D v\\_D,m^k, \\quad (4)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 72, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "371447f5-b816-4e32-ac4c-d9f28b65ce9f": {"__data__": {"id_": "371447f5-b816-4e32-ac4c-d9f28b65ce9f", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 10](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "57744f10-0a8e-4ec1-abf7-2aef02d67b09", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 10](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "33504e1492916198ddeb2841888e4b4e12452e3e069c410832a0e681bf7f2a1f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "where \\kappa\\_D, \\beta\\_D, and L\\_0D,m denote the diagonal spring constant, damping constant, and rest length, respectively, the latter given by L\\_0D,m = \\sqrt{L\\_seg^2 + (R\\_m + R\\_m+1)^2}; the length of the diagonal element is L\\_D,m^k.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 239, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "caf382e1-e126-40a5-9f74-dd91569b9def": {"__data__": {"id_": "caf382e1-e126-40a5-9f74-dd91569b9def", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 11](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0d04e6b9-1d91-499e-906a-33c95d91a189", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 11](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "5767c23334337f03ca8031b23d6c9737befc4bc391813af3e61b152e57cba676", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The parameters for the passive body were chosen by comparing the behavior of the passive physical model embedded in virtual water and agar environments to that of a flaccid *C. elegans* in water or on agar (Sauvage, 2007). Accordingly, a model worm initiated in a bent position will straighten almost instantaneously in water but will straighten only very slowly on agar. These parameters are given in **Table 1**.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 414, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f0c03f6e-c3e7-4758-aab0-02347d0ba634": {"__data__": {"id_": "f0c03f6e-c3e7-4758-aab0-02347d0ba634", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 12](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "79943ee1-c288-46db-b127-d7960022d8d3", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 12](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "b3d9f7626057ad3f054836f2376573ba4b85a36df1f5ee9cd15c8c5037d623f3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Active muscle forces", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 24, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b9feeb5a-43ed-41dd-a61f-f55edd043fe5": {"__data__": {"id_": "b9feeb5a-43ed-41dd-a61f-f55edd043fe5", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 13](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "dc2d888c-80d3-48d3-8ff9-a8fa6c96679a", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 13](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "02aa734e2c3e41ce3fefbc06136f27d89db4ada66d893c932b7c02864aac95f6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The worm's longitudinal body wall muscles are anchored to the inside of the cuticle and are effectively grouped into dorsal and ventral sets. In the model, muscles connect adjacent points on the same side of the body, and therefore act in parallel with the passive lateral elements representing the cuticle (**Figure 1B**). Thus, the muscle length and cuticle length for a given section of the body are assumed to be identical, consistent with recent experimental", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 463, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c5715c1a-07a5-47e1-8477-f54110143acb": {"__data__": {"id_": "c5715c1a-07a5-47e1-8477-f54110143acb", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 14](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2b8a2405-6ce9-400f-b4ea-ae9f204893b4", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 14](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "e436255420934a74f43437dc0e20cb40df23a6e9df60e6493509dbab4152aaf9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "springs whose spring \"constant,\" rest length, and damping \"constant\" are functions of the level of activation. This implementation endows the muscles with simplified Hill-like length-force and speed-force relations (Hill, 1938), as illustrated in **Figures 2A,B** respectively.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 277, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "dea652e2-fb6b-45ff-abe4-88b26785bd95": {"__data__": {"id_": "dea652e2-fb6b-45ff-abe4-88b26785bd95", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 15](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e361afa3-cc98-4a24-a00c-11359fc3bf00", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 15](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "ebd72117f9534e2d16f9c3f9bd8e032ea639535e150df3585ca49b89b198d93c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Structure", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 13, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "db1af530-9fcf-49db-beb2-14260e922699": {"__data__": {"id_": "db1af530-9fcf-49db-beb2-14260e922699", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 16](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9be6c6bd-f831-4b20-95d4-47089c1937a6", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 16](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "7edbfaf941b806ff8a0813ee57a19f20ddba9f33c0dded38a381c90e0819577b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In the model, a worm of length L and radius R is represented by P = 2(M + 1) = 98 discrete points p\\_i^k, where i = 1, \\dots, M + 1 and k = {D, V}. In other words 49 dorso-ventral point pairs i = 1, \\dots, M + 1 form the boundaries of the M = 48 segments. The model approximates the tapered shape of the worm as a prolate ellipse. To avoid zero-valued radii at the ends, the major radius is taken to be slightly greater than L/2. For a minor radius R, the radii along the body are given by", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 489, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f34a4d99-7f13-4440-8e95-aa69c77897a8": {"__data__": {"id_": "f34a4d99-7f13-4440-8e95-aa69c77897a8", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 17](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d5c570c1-78e1-489a-ae53-cc7fe93e82a8", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 17](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "365f91cf91438a5046158d15694a72a072d29de4b605cef838faf269d266fe90", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "R\\_i = R \\left| \\sin \\left\\[ \\cos^-1  \\frac{i - (M/2 + 1)}{M/2 + 0.2}   \\right|. \\quad (2)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 90, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "076d9dbc-6f50-4a1a-a0b4-0bb78d5335ec": {"__data__": {"id_": "076d9dbc-6f50-4a1a-a0b4-0bb78d5335ec", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 18](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fe2d0516-ca99-47a1-bc4c-8f5c69db4e10", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 18](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "0c0889fb6222d4085bfbbadf2fda80d908ba6495ca8f8da52d0fa2bee706054f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Neglecting the worm's radial elasticity implies the body will maintain a fixed diameter over time. This allows opposite points p\\_i^k and p\\_i^\\bar{k} to be connected by a solid rod of length 2R\\_i (with \\bar{k} denoting the", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 224, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f185873d-2610-4ac0-ac0c-bc2c9e120495": {"__data__": {"id_": "f185873d-2610-4ac0-ac0c-bc2c9e120495", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 19](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "061e103e-6f2f-481c-bbbd-378fa435e9d0", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.3, para 19](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "37f49be9a2b2afd4f3daa44b23195f6999b85bda7d6a922327abb1c1ecf5bd0a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Frontiers in Computational Neuroscience | www.frontiersin.org | March 2012 | Volume 6 | Article 10 | **3**", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 106, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1591af56-af33-454f-8219-ee66fdc48cce": {"__data__": {"id_": "1591af56-af33-454f-8219-ee66fdc48cce", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.4, para 2](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a73381ca-c639-494c-90c7-c6387390e944", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.4, para 2](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "01965699af6c575b8986823c9c28e7a866bae62929adedab47673c499913bfe7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|A|B|||\n|-|-|-|-|\n|-fkM,m (\u00b5N) vs LkL,m / Lk0L,m|-fkM,m (\u00b5N) vs vkL,m (mm/s)|||\n|0|-8|-0.1|0|\n|0.5|-4|-0.05|\\~1.2 (for V=0.25) to \\~5 (for V=1)|\n|1|0|0|\\~2.5 (for V=0.25) to \\~10 (for V=1)|\n|1.5|4|0.05|\\~3.8 (for V=0.25) to \\~15 (for V=1)|\n||(Linear relationship with activation VkM,m = 0.25, 0.5, 0.75, 1)|0.1|\\~5.2 (for V=0.25) to \\~21 (for V=1)|", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 348, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7a544cbb-bf63-4a53-a6d5-a92d5e183e90": {"__data__": {"id_": "7a544cbb-bf63-4a53-a6d5-a92d5e183e90", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.4, para 3](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "faf65f23-e0f7-435b-a7bb-e2f06fa2a7e3", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.4, para 3](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "5f709edeef61c1860fbc2681d0c4f1f1c7ccae0efd23a0048eb65c6754d9c7a6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**FIGURE 2 | The force generated by model muscles is a function of their activation, length, and rate of contraction.** (A) Force/length relationship obtained by holding the muscle at a specific length. (B) Force/velocity relationship obtained by allowing the muscle to contract at a specified rate and measuring the force it exerts at the moment it reaches its rest length L\\_0L. The model therefore provides a simple linear approximation of these properties of biological muscles. Note that in both cases -f is plotted for simplicity, because contractile forces are defined as negative in the model.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 601, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3dd26236-0d9f-4cea-b4da-a4f3b0222d2e": {"__data__": {"id_": "3dd26236-0d9f-4cea-b4da-a4f3b0222d2e", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.4, para 5](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ed74e126-e7d1-43f7-9495-80f79342dda5", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.4, para 5](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "9dd7d92d916002cdbefa49a16d0fdac12ca6113c7735f74843fa81aa2644e4fd", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Param.|Value|\n|-|-|\n|M|48|\n|L|1 mm|\n|\u03baL|\\frac{M}{24} 0.01  kg \\cdot s^-1|\n|\u03baD|\\kappa\\_L \\times 350|\n|\u03ba0M|\\kappa\\_L \\times 20|\n|Fmax,1|0.7 \\times (2/3)|\n|P|2 \\ (M + 1)|\n|\u0394M|0.65|\n|L0L,m|\\sqrt{L\\_seg^2 + (R\\_m - R\\_m+1)^2}|\n|L0D,m|\\sqrt{L\\_seg^2 + (R\\_m + R\\_m+1)^2}|\n|Lmin,m|L\\_0L,m \\ (1 - \\Delta\\_M \\ (R\\_m + R\\_m+1) / 2R)|\n|Fmax,m=2,...,M|0.70 - 0.42 \\ (m - 1) / M|\n|R|40 \\ \\mum|\n|Lseg|L/M|\n|\u03b2L|\\kappa\\_L \\times 0.025  s|\n|\u03b2D|\\kappa\\_D \\times 0.01  s|\n|\u03b20M|\\beta\\_L \\times 100|", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 479, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "db67b09c-e43b-40c9-8cf1-dee2d6b51ef8": {"__data__": {"id_": "db67b09c-e43b-40c9-8cf1-dee2d6b51ef8", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.4, para 6](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4764a6aa-2b8b-43d9-b0d1-f267884e27a3", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.4, para 6](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "96a212d6d2fb19d2a4a0ac2539271f53c9ae001dc887f9fc0817ef6df3058ef7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "findings (Petzold et al., 2011). Qualitatively following Hill's relations (Hill, 1938), muscle forces are modeled as a function of the muscle activation and mechanical state (**Figure 2**), such that (i) as a muscle shortens the maximum force it can develop will decrease, eventually reaching saturation, and (ii) the force it generates varies inversely with the speed of contraction. Accordingly, muscles are implemented as a variable lateral element (again consisting of a spring acting in parallel with a damper), whose spring parameter \\kappa^k\\_M,m (equivalent to the spring \"constant\" in an ideal Hooke's Law spring), spring rest length L^k\\_0M,m, and damping coefficient \\beta^k\\_M,m all depend on the muscle activation. An anterior-posterior gradient in the maximum muscle efficacies is implemented by a linearly (posteriorly) decreasing factor F\\_max,m. This gradient makes the shape of the worm more biologically realistic (see **Figure 3**). Finally, the most anterior muscles receive somewhat weaker innervation to prevent the tip of the head from displaying unrealistically strong bending. Muscle forces are therefore given by", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1139, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f0a08a31-ce5a-4513-9380-d6609d47a45d": {"__data__": {"id_": "f0a08a31-ce5a-4513-9380-d6609d47a45d", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.4, para 7](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "57763666-b959-4295-9009-a887880eaa1b", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.4, para 7](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "3d6cc13a98d830a97497d4ee88f79a0f18e7086e87372c72c2cd45c9a7ea9937", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "f^k\\_M,m = \\kappa^k\\_M,m  L^k\\_0M,m - L^k\\_L,m  + \\beta^k\\_M,m v^k\\_L,m, \\tag{5}", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 80, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "904a41ae-06e7-442b-a767-4865f7fa271e": {"__data__": {"id_": "904a41ae-06e7-442b-a767-4865f7fa271e", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.4, para 9](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5c0ca6e3-789f-4c22-9e6c-2be235e7279a", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.4, para 9](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "075d7616f243a84f0347aeb0317e9b9b6954cf5353057344b45d387d36d92168", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "\\begin{aligned} \\kappa^k\\_M,m &= \\kappa\\_0M \\ F\\_max,m \\ \\sigma  A^k\\_M,m  \\ L^k\\_0M,m &= L\\_0L,m - F\\_max,m \\ \\sigma  A^k\\_M,m  (L\\_0L,m - L\\_min,m) \\ \\beta^k\\_M,m &= \\beta\\_0M \\ F\\_max,m \\ \\sigma  A^k\\_M,m , \\end{aligned} \\tag{6}", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 231, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "79efa600-58df-4c4f-9135-92ba998a52d2": {"__data__": {"id_": "79efa600-58df-4c4f-9135-92ba998a52d2", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.4, para 10](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c0ed365b-06cc-4f49-b861-a9bbbdc18ffa", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.4, para 10](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "fee2a85a5713ad1b99bdaec5086ccc192a37e423c7f362b50c69a17e6e2fb105", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "and where \\kappa\\_0M and \\beta\\_0M are constants. The function \\sigma is a piecewise linear approximation of a sigmoid that binds the muscle's electromechanical response to the allowable range", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 192, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a2f15b76-0bcd-42a1-a7dc-57d14a4018c4": {"__data__": {"id_": "a2f15b76-0bcd-42a1-a7dc-57d14a4018c4", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.4, para 11](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2024e046-29dd-4fed-906f-dafa05062aa4", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.4, para 11](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "a966efec6748947ebdf8c6683e8afe9334f302a341f7211166420b176ba4bc4c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "\\sigma(x) = \\begin{cases} 0 & , & x \\le 0 \\ x & , & 0 < x < 1 \\ 1 & , & x \\ge 1. \\end{cases} \\tag{7}", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 100, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4d493451-cbb1-49cb-b521-f840ded78210": {"__data__": {"id_": "4d493451-cbb1-49cb-b521-f840ded78210", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.4, para 12](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "899e4c2e-bc08-481b-9da3-c05990dc8335", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.4, para 12](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "5f293cf9fdcfa2f147c3424dff56c5c6305c67acb7ba9ff09421f20fbdc9036a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "A minimum muscle length L\\_min,m prevents the muscles from contracting unrealistically. To allow the same curvatures to be", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 122, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ab07dade-975a-4582-8fcc-88eaf4777bb4": {"__data__": {"id_": "ab07dade-975a-4582-8fcc-88eaf4777bb4", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.4, para 13](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cdbf47a2-fbba-4886-8b47-ccb716cf26a8", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.4, para 13](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "ede2572937173dda34c512f472ee452044f11e6246f2f021d8f8ef7201ebd30f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Frontiers in Computational Neuroscience | www.frontiersin.org | March 2012 | Volume 6 | Article 10 | 4", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 102, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "90ef9fb5-4946-45c5-b48e-59ecba96b58d": {"__data__": {"id_": "90ef9fb5-4946-45c5-b48e-59ecba96b58d", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.5, para 0](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "576a7526-286c-4ea7-844b-c90f73c516e0", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.5, para 0](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "2f73e7505fb439646e33a47547a42ce72517763bc3e11314635a9107bcf28cc3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Boyle et al. Neuromechanical model of *C. elegans* locomotion", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 61, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b91a5f3c-f75d-4492-9f22-00cbcae9673c": {"__data__": {"id_": "b91a5f3c-f75d-4492-9f22-00cbcae9673c", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.5, para 1](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "09bb5672-30b6-4a87-88c0-995f8e235c35", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.5, para 1](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "2e4c585a227b193abbd7298226d2de2bebd15d5f9b853c6feb12a402e5e9e775", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "![Figure 3: Curvature gradients in experiment and model.](https://placeholder.com)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 82, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f0045ac6-a367-47aa-ba8e-3b76c5ced020": {"__data__": {"id_": "f0045ac6-a367-47aa-ba8e-3b76c5ced020", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.5, para 2](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9f48fc1a-8321-4be3-bd07-7db2cc4f2df7", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.5, para 2](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "d52bcef6385e922f3daf210eb5c628e7b28941b18b18813268f910699354251f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**FIGURE 3 | The worm\u2019s locomotion wave exhibits a posteriorly decreasing gradient in curvature, averaged over time (\\bar{\\kappa}). S is a measure of the position along the worm\u2019s body, with S = 0 corresponding to the head and S = 1 corresponding to the tail. (A)** Experimentally observed curvature gradient obtained by averaging the curvature at each point along the body, first over time (\\approx10 s) and then over several worms (n = 3 for agar and n = 5 for water). Bars indicate the standard deviation over the n worms. **(B)** Qualitatively similar curvature gradients exhibited by the model, due to the gradients in muscle efficacy and stretch receptor weighting.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 671, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7443db4a-100c-4457-a0fe-ad74d6e52ea4": {"__data__": {"id_": "7443db4a-100c-4457-a0fe-ad74d6e52ea4", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.5, para 3](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9768e67f-ee14-44e2-a9a8-2fd3a45dac3f", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.5, para 3](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "324c49b07f6a94939f599ce32e16e996b6b92856c5ca005dd65238f3bacebc3d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "attained for all segments along the worm, L\\_min,m is modulated according to the shape of the worm (see **Table 1**). Muscle parameters were chosen such that the worm was strong enough to bend its body on agar, but could not generate unrealistically tight curvature (**Table 1**).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 280, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "19a9954a-7c28-49ff-a6de-b5fb821cc22a": {"__data__": {"id_": "19a9954a-7c28-49ff-a6de-b5fb821cc22a", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.5, para 4](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "23f2cf80-fa75-4a60-a99d-7d52efce77d6", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.5, para 4](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "b3e161a6cea28cce23c71b02b20cf10b5a4259db8ea2aeeb5c8f5aff7a724c1c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### 2.3. THE NEUROMUSCULAR SYSTEM", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 33, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4f08215d-a965-4aa4-a76c-c11afac7d8e4": {"__data__": {"id_": "4f08215d-a965-4aa4-a76c-c11afac7d8e4", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.5, para 5](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4ff54d12-fd86-4f8a-b284-d71f8cd0e822", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.5, para 5](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "dfb242f0fb42acc6fd6ade0cf2ef27d5015eb04bf6d8e607db90e784d5fff7ac", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "*C. elegans* forward locomotion is controlled by head and ventral nerve cord circuits. The ventral cord subcircuit associated with forward locomotion contains four main classes of motoneurons (11 VB, 7 DB, 13 VD, and 6 DD neurons) and one key pair of interneurons (class AVB). Longitudinal body wall muscles line the body. These muscles contract and relax in the dorso-ventral plane. The individual members of each motoneuron class are arranged sequentially along the body such that their motor output regions do not overlap (White et al., 1986). In line with previous models (Niebur and Erd\u00f6s, 1991; Bryden and Cohen, 2004, 2008; Karbowski et al., 2008), we consider a simplified, symmetrized neural circuit, disregarding the asymmetry in neuron numbers, and thus allowing us to create the model as a series of repeating units. In a rough correspondence with muscle and neuron numbers (on the ventral side), we chose to model N = 12 neural units, with each controlling M/N = 4 muscle segments. These neural units are identical, except for changes in certain parameters. These simplifications are designed to aid the analysis of the circuit and its dynamics and to reduce the number of free parameters. While this approximation is reasonable for a model that is restricted to generating sinuous undulations, it may need revisiting for models to capture a richer set of behaviors, in particular where additional classes of neurons are included.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1443, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "bc7b55e0-358f-49ff-8e6c-f6355e878de6": {"__data__": {"id_": "bc7b55e0-358f-49ff-8e6c-f6355e878de6", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.5, para 6](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3dfd23e5-7713-44d7-83f2-05be0b8a7d5c", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.5, para 6](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "8ca4fa189d990eec7a06e3756e18b46406c506033af7af1d8b8b1a3224da411b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "#### The neural circuit", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 23, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "89570227-1145-46ca-92ce-7f56c195e84b": {"__data__": {"id_": "89570227-1145-46ca-92ce-7f56c195e84b", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.5, para 7](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "022c5185-fee5-4173-a1ce-1dc088c5a0fd", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.5, para 7](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "766fa67b1c9fbd4343ea469870c30642b68f09a6f52bba96ed8cf1bf42a005e3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In the worm, VB and DB neurons receive input from AVB interneurons via electrical synapses and excite muscles on the (V)entral and (D)orsal sides. DD (VD) neurons receive input from VB (DB) motoneurons and inhibit the opposing dorsal (ventral) muscles. Thus excitation of muscles on one side of the body is likely to result in inhibition of muscles on the opposite side. Chen et al. (2006) have also reported some inhibitory connections from VD to VB neurons which provide motoneuron-to-motoneuron inhibition on the ventral side. These connections do not feature in the connectivity diagrams of White et al. (1986) and are seldom discussed. In addition to these chemical synaptic connections, electrical synapses exist between adjacent VB (DB) neurons and between adjacent muscle cells (White et al., 1986; Chen et al., 2006).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 826, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "dbeafad5-3e89-47f4-a790-ffabe2619cda": {"__data__": {"id_": "dbeafad5-3e89-47f4-a790-ffabe2619cda", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.5, para 8](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "35f73592-5ed8-41d2-a73f-4c3b3e2f25e7", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.5, para 8](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "ce32966f382376ea7a763292e6cc3fe718eee0bb6aeecebacecb34b830f31660", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In the model, the ventral cord circuit (White et al., 1976, 1986; Chen et al., 2006) is simplified to a single AVB command neuron that drives a series of N = 12 repeating units, each containing one motor neuron of each class DBn, VBn, DDn, and VDn, with n = 1, \\dots, N (see **Figure 1C**). Note the inclusion of neural inhibition from VD to VB, that is partially consistent with the connectivity data (Chen et al., 2006). Within each unit, B-class neurons receive a constant-current input from AVB, switching the entire circuit on and off. D-class neurons are modeled as passive (linear) elements. Postulated stretch-receptor-mediated proprioception in B-class neurons forms the fundamental oscillatory mechanism of the model. Each DB (VB) neuron integrates stretch-receptor currents from the dorsal (ventral) side, both locally and posteriorly, along its axon. Finally, all electrical synapses except those between AVB and VB/DB are neglected in our model. Indeed, a modeling study on the role of inter-muscle coupling (Boyle and Cohen, 2008) suggested that the coupling may be too weak to have any observable effect and", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1122, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "18d3bdf3-fe18-4a70-bf50-f5aa456ebada": {"__data__": {"id_": "18d3bdf3-fe18-4a70-bf50-f5aa456ebada", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.5, para 9](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1d35f55c-6b7d-4d9b-b8c3-29c555f3a98d", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.5, para 9](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "c398b5cc00540b16c067e68b45d2667048da44898a5f61e417baa7b6369e354e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Frontiers in Computational Neuroscience | www.frontiersin.org | March 2012 | Volume 6 | Article 10 | **5**", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 106, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "660b052c-0574-4c1f-ba1b-5e39f7a700aa": {"__data__": {"id_": "660b052c-0574-4c1f-ba1b-5e39f7a700aa", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 1](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5eda5100-1aa7-4055-bb35-9350a5d1ff3d", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 1](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "3cab37dea1b7e5df9c0d1f20004c1bc73d862a37888e684dfee505e114ec657e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "our simulation experiments found that electrical coupling among adjacent motoneurons was similarly insignificant in the present model (data not shown).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 151, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "00d43b54-48c4-4517-bd26-d83af291b9f3": {"__data__": {"id_": "00d43b54-48c4-4517-bd26-d83af291b9f3", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 2](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "94b3afb6-3bb4-4e23-96a4-a93b1ffc0a40", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 2](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "e05f4025ec1df0d78d84fce1b72b153ac4a26b45b0adcacd696d5ae1d482b20b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Motor neurons", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 17, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "66ae2a51-30c9-43f2-82e8-a004a5f78655": {"__data__": {"id_": "66ae2a51-30c9-43f2-82e8-a004a5f78655", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 3](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b739f68f-2f24-47f2-a8c1-ad60509db102", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 3](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "f068be363c900de77dbb7898258dc1b2877ba5f54ee66415a84d2bd5e6e05fb5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Motivated by electrophysiological recordings of RMD motor neurons in the head (Mellem et al., 2008), we model B-class neurons as binary bistable elements. For simplicity, a binary variable S = {0, 1} denotes *off* and *on* states (and abstractly represents polarized and depolarized membrane potentials). Each B-neuron turns on in response to a supra-threshold input signal which includes internal activation from stretch receptors (see below) and synaptic inputs. B-neurons turn off when this signal falls below some threshold. Hysteresis is implemented by making the activation/deactivation threshold state dependent (see arrows in **Figure 7A**). Given the short time scale of RMD neurons, which we estimate to be \\le 10 ms (see Figure 2 of Mellem et al., 2008), it is reasonable to model these neurons as instantaneous.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 823, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "11982216-f379-4947-8f1d-cbdd76b52331": {"__data__": {"id_": "11982216-f379-4947-8f1d-cbdd76b52331", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 5](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "722ed3e0-eb78-4c80-a5f6-83122695f319", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 5](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "2d6fa1aa26b399813798c0770e25ff8cd2e3362266f12ea3de92fe24118b1955", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "S^k\\_n = \\begin{cases} 1 & , \\quad I^k\\_n > 0.5 + \\epsilon\\_hys (0.5 - S^k\\_n) \\ 0 & , \\quad otherwise , \\end{cases} \\tag{8}", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 124, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0ab8764e-a1ef-4605-b63c-02896188368d": {"__data__": {"id_": "0ab8764e-a1ef-4605-b63c-02896188368d", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 6](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4c7f394d-ce0e-4e6e-a91e-dba80d6f1570", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 6](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "66717ba9e230e83509f9f5e73533efc79ef5cece53642f713f535d15058d6f52", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "where S^k\\_n is the neuronal state variable for the nth neuron on side k; \\epsilon\\_hys sets the width of the hysteresis band; and I^k\\_n is the total input (or \"electrical current\") into the neuron in question. Hysteresis is achieved by introducing state-dependent activation and deactivation thresholds 0.5(1 \\pm \\epsilon\\_hys). This prevents oscillations of arbitrarily small amplitude and, in conjunction with the stretch receptor weight, controls the extent of body bending. Each D-class neuron is excited by a single B-class neuron and assumed to respond instantaneously (with state S^\\bar{k}\\_n).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 603, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "50dd2161-c595-496f-b1a4-f8f3d6144c33": {"__data__": {"id_": "50dd2161-c595-496f-b1a4-f8f3d6144c33", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 8](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "43f71032-9e43-42d4-a14d-33ffadf8eaa1", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 8](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "160882671c826cd95d02c15498566e5aeb6b44e4162f7bea0a3457f36196d960", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "I^k\\_n = I^k\\_AVB + I^k\\_SR,n + w^k\\_- S^\\bar{k}\\_n ,", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 53, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d39c52a5-d5f3-47f5-b461-864e4b412780": {"__data__": {"id_": "d39c52a5-d5f3-47f5-b461-864e4b412780", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 9](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4722d03a-9a58-4d48-91e2-460ec9ccb2c5", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 9](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "67ffeca97229e79c785ac1609560b7df6a17bcbc7d1c4ba0e60ef89dbd0ca187", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "where I^k\\_AVB (a constant input current from forward locomotion command interneurons AVB) differs for dorsal and ventral neurons; I^k\\_SR,n is the stretch receptor (SR) current; and w^k\\_- sets the inhibitory (GABAergic) synaptic weight. Note that only ventral neurons receive inhibitory synaptic inputs (w^D\\_- = 0).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 318, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "49a5fcaa-04db-4fe3-a150-63bc03afe5a2": {"__data__": {"id_": "49a5fcaa-04db-4fe3-a150-63bc03afe5a2", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 10](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2a33eac8-34c2-4bea-b507-cef3de4b7858", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 10](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "603088fd1be7add249a441c61dec0ca36123bef753b9fdd65dee7dec5ccacd32", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Stretch receptors", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 21, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fa103e0f-eae4-496b-9600-e3fd7d57b801": {"__data__": {"id_": "fa103e0f-eae4-496b-9600-e3fd7d57b801", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 11](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "35652bb0-8743-4e86-afb4-19cac35a9b70", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 11](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "9cdf875465b6a112d08f29dc64697d793b639cd511f4d33cea610ff741aa1286", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Mechanosensory feedback and its importance in the regulation of locomotion has been reported in *C. elegans* interneurons (Li et al., 2006). While direct evidence for proprioception is still lacking in the motoneurons themselves, mechanosensitive stretch receptor channels have long been postulated to exist in B (and A) class motoneurons. This suggestion was originally motivated by the morphology of these neurons, specifically their long, posteriorly directed undifferentiated processes on which no synapses are found (White et al., 1986). Indeed, the stretch receptor hypothesis is widely recognized as an attractive and plausible conjecture (Riddle et al., 1997; Tavernarakis et al., 1997; Bryden and Cohen, 2004, 2008; O'Hagan and Chalfie, 2005; Karbowski et al., 2008) and forms the basis of our model. The proposed mechanosensitive channels in these processes would respond to the changes in length associated with body bending. In our model, stretch receptors integrate over local and posterior body segments, in line with the anatomy.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1044, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9de2374d-d2ee-412a-af86-01070d97ea91": {"__data__": {"id_": "9de2374d-d2ee-412a-af86-01070d97ea91", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 13](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0cd1a242-1f75-4a12-adf6-f52bb9b465b3", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 13](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "7860345b4dd81894281dcf0f3002070522d0ad7ee428ca8c0d482e0fde3c13e9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "I^k\\_SR,n = A\\_n G\\_SR,n \\sum\\_m=(n-1)N\\_{out+1}^s h^k\\_m \\tag{9}", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 65, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1523f031-e2e9-457b-8537-abe833699ffe": {"__data__": {"id_": "1523f031-e2e9-457b-8537-abe833699ffe", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 14](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7a0bc5a9-a64f-43df-ba43-9b4840f72686", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 14](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "38f5d8f0e009390c62b2c99760c29f2abbebedcbd913f0ff7bc9188883f009c0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "sums over contributions from a number of segments m of the physical model, where s = \\min{M; N\\_SR + (n - 1) N\\_out} sets the number of segments sensed to either N\\_SR or to the number of remaining posterior segments. A prefactor", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 229, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2ff946af-c44c-493e-94fb-1d23039ed0aa": {"__data__": {"id_": "2ff946af-c44c-493e-94fb-1d23039ed0aa", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 15](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f8847215-4ed8-4dc0-a7eb-6e1c941a0a24", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 15](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "3ad19f3f683bc59ce9cee204952e30e2182a1ce13e44dce36a526bf225a25790", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "A\\_n = \\begin{cases} 1 & , \\quad (n - 1) N\\_out \\le M - N\\_SR \\ \\sqrt{\\frac{N\\_SR}{(M - (n - 1) N\\_out)}} & , \\quad (n - 1) N\\_out > M - N\\_SR \\end{cases} \\tag{10}", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 163, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "50a584a5-ad28-4e0c-b0e2-b1f34cbdc34f": {"__data__": {"id_": "50a584a5-ad28-4e0c-b0e2-b1f34cbdc34f", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 16](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4ac0146e-055f-4562-bc08-b0c96da0d073", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 16](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "2ce33ce347a902e7d01153de29d525f3d9ea50750dfaa67b9c3284020785561c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "compensates for the variable number of contributing segments. The conductance parameter G\\_SR,n increases linearly from head to tail to compensate for the decreasing curvature of undulations down the worm, imposed by the gradient in muscle efficacy. Finally, h^k\\_m is the effective stretch receptor activation function. We allow the stretch receptor conductance to generate a depolarizing response to stretch and a polarizing response to compression, relative to the local segment resting length. (A similar effect could be achieved in the worm with stretch sensitive channels that are partially open at the rest length.) For simplicity, we take this function to be linear (bilinear) on the ventral (dorsal) sides:", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 715, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e112c982-9eea-4122-b0b5-dbf43e462c93": {"__data__": {"id_": "e112c982-9eea-4122-b0b5-dbf43e462c93", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 17](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0944b622-c7ce-42d6-8a78-033ac6d46b58", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 17](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "450d62e98a960fa08c786ffd4ca8241d037ab200854be50f68fb327874edbc3b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "h^k\\_m = \\lambda\\_m \\gamma^k\\_m \\frac{L^k\\_L,m - L\\_0L,m}{L\\_0L,m} , \\tag{11}", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 77, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "65fdcb50-54d7-40c5-96a8-a4b32c64cf73": {"__data__": {"id_": "65fdcb50-54d7-40c5-96a8-a4b32c64cf73", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 18](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "47f8307a-8599-4774-894e-6b627de52c0a", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 18](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "ddfb0068c3b0e22b595c65ed05218af283651c286185d8a1efb431823cc88518", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "where L\\_0L,m is the segment rest length and L^k\\_L,m is the current length of the kth side of the mth segment. Here,", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 117, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6e0ed487-c1ea-4e85-948f-446b64d5fe4a": {"__data__": {"id_": "6e0ed487-c1ea-4e85-948f-446b64d5fe4a", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 20](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "325b92a7-7dbe-4d13-90f1-312743a260c3", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 20](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "1d9d32b24caeed9116ab9dcacf388d6a8f6a91e9124b0cf245551a6ce582ee47", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "is required due to the elliptical shape (and variable radius) of the body, and", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 78, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fd3aae3b-f060-4a63-b54b-e65b3474b58d": {"__data__": {"id_": "fd3aae3b-f060-4a63-b54b-e65b3474b58d", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 21](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "dd5727e4-5f1b-45dc-b507-150975a1ee51", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 21](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "12f7f3aaac0fefc6eaebfcb05b058d55ff4ccf7c398817f16af94213f04bc0a4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "\\gamma^k\\_m = \\begin{cases} 1 & , \\quad k = V \\ 0.8 & , \\quad k = D; L^k\\_L,m > L\\_0L,m \\ 1.2 & , \\quad k = D; L^k\\_L,m < L\\_0L,m \\end{cases} \\tag{13}", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 150, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "58913925-8be9-48fa-9082-6a5c5e4fea81": {"__data__": {"id_": "58913925-8be9-48fa-9082-6a5c5e4fea81", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 22](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "90dad99f-4591-4e7f-919f-f996621c31bd", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 22](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "6dc29b6c3586519e66c81b934c589e545fac7586932610e67c66da7af8380583", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "modifies the dorsal stretch receptors to ensure that the worm will move straight despite the asymmetry in the neural circuit.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 125, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "dc5592be-8496-49b5-95b8-7f73a2ccf7c6": {"__data__": {"id_": "dc5592be-8496-49b5-95b8-7f73a2ccf7c6", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 23](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a0c273d5-77b6-4195-9596-b42bf0d364f7", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 23](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "aa97561a8df7dc6904bb9c81f196f269ff3f4ba8d1c46d5ea670a8749849601a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Conductance-based neurons", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 29, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ce6d1c83-d212-47e3-a05d-44e08cd9fdf7": {"__data__": {"id_": "ce6d1c83-d212-47e3-a05d-44e08cd9fdf7", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 24](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "dda10c68-e457-4987-8b94-2599774b6b7f", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 24](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "2dd18b5b3c4ee9dc5e5f31f6db9d20fc70d258c9251997581549447bbd23268b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The neural model presented above makes use of two key simplifications, namely treating the neurons as binary and instantaneous. However, it could certainly be argued that a mechanism that works with simple binary neurons would not necessarily work with more realistic continuous-valued (and non-instantaneous) neurons. To validate the binary model, we developed a conductance-based model of the B-class neurons based on the RMD dynamics presented in Mellem et al. (2008).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 471, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "17492614-0d9e-409d-9054-3a134a78b9bb": {"__data__": {"id_": "17492614-0d9e-409d-9054-3a134a78b9bb", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 25](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5aa29ad5-0a40-48c7-9d97-5f7136823077", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.6, para 25](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "d71ba530435f97395ec42ad3740912bd5cdac7c6fb16b58d1777cce04595fc27", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Frontiers in Computational Neuroscience | www.frontiersin.org | March 2012 | Volume 6 | Article 10 | 6", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 102, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "de4c7110-f257-4e1f-a1a9-8659bc7e393c": {"__data__": {"id_": "de4c7110-f257-4e1f-a1a9-8659bc7e393c", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 0](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c9935a88-a557-4955-83d9-33e347092e8a", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 0](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "e8bb29aa1b51424efaa43e4462afdb7049e1e185f1d0401dcfab01c43d5dbfe5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Boyle et al. | Neuromechanical model of *C. elegans* locomotion", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 63, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "680db4e9-956c-4c06-921f-0e619850b059": {"__data__": {"id_": "680db4e9-956c-4c06-921f-0e619850b059", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 1](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c03383f1-f18d-4c8a-b1f9-caf522a23f28", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 1](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "8143e1f24b9f210f53adcadb8e7b3a7d2a39701238d97928fcbe08d855e6135d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We begin by replacing the binary neural states S\\_n^k, which were updated according to equation (8), with continuous-valued membrane potentials V\\_mem,n^k which evolve according to", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 180, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3d3cda1e-cdce-4420-a07b-fef65447a32d": {"__data__": {"id_": "3d3cda1e-cdce-4420-a07b-fef65447a32d", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 2](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0fa9b9ab-4ab4-4546-b512-b89421fd2aca", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 2](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "f26e51dea710e0731afeb92732b1fda23b5537382ba644266a732cfa402eda90", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "C\\_mem \\frac{dV\\_mem,n^k}{dt} = -I\\_leak,n^k + I\\_act,n^k + I\\_SR,n^k + I\\_AVB,n^k + I\\_inh,n^k, \\quad (14)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 107, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "20db3681-68f5-4951-8964-3cb923a1e454": {"__data__": {"id_": "20db3681-68f5-4951-8964-3cb923a1e454", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 3](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "440a5fe3-6973-416c-a30f-54de74a1ebfa", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 3](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "89d26ed1c927cf4c9719997e9a084aaa298b0c6045c45f1e3a892a7996f256e5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "where C\\_mem is the membrane capacitance, and the individual terms in these equations are as follows:", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 101, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8fecf660-f6be-4673-8710-9f0d2ee16f6d": {"__data__": {"id_": "8fecf660-f6be-4673-8710-9f0d2ee16f6d", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 5](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "313720d1-a92b-4aef-a6c8-8fc60c974045", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 5](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "288112d560e993c3781d125921dd11573205dfbb89763ba51dcfa69f584c3110", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "is the leak current, where G\\_mem and V\\_rest are the membrane leak conductance and reversal potential respectively.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 116, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fbceee69-935e-4cfc-82a7-78dc9f96c30a": {"__data__": {"id_": "fbceee69-935e-4cfc-82a7-78dc9f96c30a", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 7](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f3dab8cc-e341-4342-b8d0-b153c485213f", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 7](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "cd198cdded48ddb9a2ca2f4f70eae51616af1e884afceb74bf7b549d191310d8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "is a state dependent self-exciting current responsible for the bistability, with a maximum conductance G\\_act and activation function parameters k\\_act and V\\_act.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 163, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "eef01856-b5ac-47f2-b631-0dac6b57e1a2": {"__data__": {"id_": "eef01856-b5ac-47f2-b631-0dac6b57e1a2", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 9](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "54f5dfe3-d7fe-43ae-ab89-3599da686902", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 9](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "eab1a06da32a695e8f925d99d055fe788bbe919d18c151ddb74f48a9e7f01770", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "is the external AVB input, where G\\_AVB is the corresponding gap junction conductance, V\\_AVB is the AVB membrane potential; the bias current I\\_bias^k is responsible for breaking symmetry between dorsal and ventral neurons (and is set to 0 dorsally). The inhibitory input is set to 0 dorsally and is given by", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 309, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "59dbfb10-6273-4884-8de2-9b6025a9295b": {"__data__": {"id_": "59dbfb10-6273-4884-8de2-9b6025a9295b", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 10](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ed66b2a2-5324-441a-b630-291648b2a15e", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 10](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "3c819371ff4dfe4fc67c2aa3915c25e98c42c20a1c18ec07539fe66cd03e1d87", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "I\\_inh,n^V = -\\frac{G\\_GABA}{1 + e^-k\\_GABA(V\\_{mem,n^D - V\\_0,GABA)}}", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 70, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "eda99ef2-f037-48e4-a6fe-25fea251174c": {"__data__": {"id_": "eda99ef2-f037-48e4-a6fe-25fea251174c", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 11](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0df76e53-d11d-442f-a5ad-91b138b62305", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 11](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "f1be8273105f898159f98c401dafdc5ec8d31a90b929430842c2a8d8edf60ebf", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "on the ventral side, where G\\_GABA is the maximum synaptic conductance for neural inhibition and k\\_GABA and V\\_0,GABA are the corresponding activation parameters. Finally, the muscle inputs that would otherwise be given by equation (16) are replaced by", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 253, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "eea84ef4-2b14-4c78-8b36-e7d551de5774": {"__data__": {"id_": "eea84ef4-2b14-4c78-8b36-e7d551de5774", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 12](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "911bd561-ebac-43e9-874e-3108c3c07311", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 12](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "9f3ade6424ef5ff6808c49d84113c7b8161cd4c3744c07b9f000941f907906c8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "I\\_NMJ,m^k =  \\frac{w\\_ACh}{1 + e^-k\\_NMJ  V\\_{mem,n(m)^k - V\\_0,NMJ }} + \\frac{w\\_GABA}{1 + e^-k\\_NMJ  V\\_{mem,n(m)^\\bar{k} - V\\_0,NMJ }} , \\quad (15)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 151, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0e06c9b1-e2ec-458d-a407-e4c01f57448b": {"__data__": {"id_": "0e06c9b1-e2ec-458d-a407-e4c01f57448b", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 13](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "743e6d28-cadb-43fd-a8e1-d164a388bccc", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 13](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "89585f0783f309713d6a06341fce7e8ce45f87fabe336dba45d0807aa5a0f11f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "where the w\\_ACh and w\\_GABA set the weights of the excitatory (ACh) and inhibitory (GABA) neuromuscular junctions, and the parameters V\\_0,NMJ and k\\_NMJ determine the NMJ activation function. Parameter values for the conductance-based model are given in **Table 2**.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 268, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "45696900-6152-4784-bb02-39c3572cf8c5": {"__data__": {"id_": "45696900-6152-4784-bb02-39c3572cf8c5", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 14](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4cac918d-1c2c-43eb-9995-039765317a9d", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 14](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "cc38c01a1184eae2150da0a68dcae7530b1922a90d730f1afac08fca7cb128b7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Muscle electrophysiology", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 28, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b8f51f35-4c5e-474e-a76f-645423ea5013": {"__data__": {"id_": "b8f51f35-4c5e-474e-a76f-645423ea5013", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 15](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ff21296e-4f72-4cbc-8059-2529d08074a9", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 15](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "569e1438d492c6d9cd411f30bb3b273c8b91294acbb1fb8f2252f968e54e41c5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Ventral (dorsal) muscle cells m receive both excitatory and inhibitory current inputs from the local VBn (DBn) and VDn (DDn) motor neurons n(m) = ceil\\[m/N\\_out] (with each neuron outputting to N\\_out = 4 muscles). The total input \"current\" to the", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 247, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "58cff19c-3b58-441a-be6f-a09cd44c841a": {"__data__": {"id_": "58cff19c-3b58-441a-be6f-a09cd44c841a", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 17](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f24e2df6-5377-4743-9781-1dca73555a6f", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 17](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "bbf9db5f1f2a144375fff03354b31e51ecd59488d1d47793ffda0addacf915d6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Param.|Val.|\n|-|-|\n|Gmem|500 pS|\n|Gact|20 pS|\n|GGABA|10 pS|\n|wACh|3|\n|wGABA|-0.5|\n|IVbias|8 pA|\n|Cmem|1 pF|\n|kact|500|\n|kGABA|100|\n|kNMJ|50|\n|GAVB|150 pS|\n|IDbias|0|\n|Vrest|-72 mV|\n|Vact|-60 mV|\n|V0,GABA|Vrest|\n|V0,NMJ|-22 mV|\n|VAVB|-87.5 mV|", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 243, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0c789f42-46a8-447a-908e-880d05e1c0ae": {"__data__": {"id_": "0c789f42-46a8-447a-908e-880d05e1c0ae", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 18](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "28f6dac2-7593-4f06-88f5-092909dfe276", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 18](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "88be798a94cd64ba7fecb9460b89ca2dd61640385c7bf8ae5675e5bdb72623ff", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "*Any parameters not given here are the same as in the binary model.*", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 68, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a98d2902-0915-4556-9dcd-2705468cfe56": {"__data__": {"id_": "a98d2902-0915-4556-9dcd-2705468cfe56", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 20](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a114b7ae-b8c2-4432-9668-7b35fad59608", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 20](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "963c87328b07ec14f292f5bf38c158698e14d30a9e7157bab17ce509a9d27e6b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Parameter|Value|\n|-|-|\n|N|12|\n|M|48|\n|NSR|M/2|\n|Nout|M/N|\n|wV|-1|\n|wNMJ|1|\n|\u03c4M|100 ms|\n|\u03f5hys|0.5|\n|IVAVB|1.175|\n|IDAVB|0.675|\n|GSR,n|(0.224 + 0.056n)/Nout|\n|wD|0|\n|w\u0304NMJ|-wNMJ|", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 177, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0f46b53c-e343-4f18-9442-15f3c473ee06": {"__data__": {"id_": "0f46b53c-e343-4f18-9442-15f3c473ee06", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 22](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "379fed02-3610-4002-b93c-f5ffa40d50a7", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 22](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "0438f8362ac0a46472a4175e7963867797d8e0fe4545f9badd6145bfb7d0f524", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "I\\_NMJ,m^k = w\\_NMJ S\\_n(m)^k + \\bar{w}*{NMJ} S*{n(m)}^\\bar{k}, \\quad (16)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 74, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "304814de-4561-4a20-a287-8c0e816a55a2": {"__data__": {"id_": "304814de-4561-4a20-a287-8c0e816a55a2", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 23](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "46d334ac-80af-4c15-9659-01f3370569d0", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 23](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "a86e0de849e0422d5d2db5908734eb76779452119dfd5ba77a590f1db64c837b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "where w\\_NMJ are the excitatory neuromuscular junction (NMJ) weights and \\bar{w}*{NMJ} = -w*{NMJ} denote the strength of GABAergic muscle inhibition by D-class neurons (**Table 3**).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 182, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5cf56d6d-4bca-4cbc-9047-dd1264289f4e": {"__data__": {"id_": "5cf56d6d-4bca-4cbc-9047-dd1264289f4e", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 24](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9b0ce2a3-ccd7-4fe2-877b-439a14e7030e", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 24](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "c9030ba39c7ddb5eb6d23a4fbd2d7d470fbc76a3151fdc5ccdc3a21bfeb4a7f6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Muscles respond as leaky integrators with a characteristic time scale of \\tau\\_M = 100 ms, which crudely agrees with response times of obliquely striated muscle (Milligan et al., 1997). The muscle activation is represented by the unitless variable A\\_M,m^k that evolves according to", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 282, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4428c960-bbbc-4763-8f6c-5445b0b666f4": {"__data__": {"id_": "4428c960-bbbc-4763-8f6c-5445b0b666f4", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 25](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7853e5bf-e96f-4fb7-9b2a-15f61329dade", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 25](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "47e5140d67b819fa16eddcc6d4d3a539787ec11c14924623e7e9fe7bfa451076", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "\\frac{dA\\_M,m^k}{dt} = \\frac{1}{\\tau\\_M} (I\\_NMJ,m^k - A\\_M,m^k), \\quad (17)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 76, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7fac02cc-5c2a-433a-ab36-08aaee683f7e": {"__data__": {"id_": "7fac02cc-5c2a-433a-ab36-08aaee683f7e", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 26](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2e015980-e52b-495f-9727-7dbb126988ad", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 26](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "f0a935755286da52cc7a6bcaa2afb6cdc0854fa2534b2eb066ccc9e4797a5027", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "where I\\_NMJ,m^k is the total current driving the muscle.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 57, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c5eb8cfb-8e1d-491e-9711-53a2b7132d2c": {"__data__": {"id_": "c5eb8cfb-8e1d-491e-9711-53a2b7132d2c", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 27](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8efa7d50-f3c5-4fca-bfa5-150249418840", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.7, para 27](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "30248defebd3549650dde9adc6b8f1b562d28b92298c72b91e8f4e14b73f4fe9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Frontiers in Computational Neuroscience | www.frontiersin.org | March 2012 | Volume 6 | Article 10 | 7", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 102, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cdfe9aea-b731-45e1-ade3-da2de0594cd1": {"__data__": {"id_": "cdfe9aea-b731-45e1-ade3-da2de0594cd1", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.8, para 0](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "77cd582a-fcdb-4f1c-97f4-71298721bfe2", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.8, para 0](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "c8b1b7cc63a00ce08359295a12f9fb039640168f0b4da9c2bf5da064a0c5d745", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Boyle et al. Neuromechanical model of *C. elegans* locomotion", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 61, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "35d930e4-dc11-4cce-97ca-bf077dd46559": {"__data__": {"id_": "35d930e4-dc11-4cce-97ca-bf077dd46559", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.8, para 1](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "32df29c2-6f6d-4639-a1a2-b297b9614510", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.8, para 1](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "1f329e41f7190986bdb91e8f5ef04313df1b12332bdb876f0e7fa8b0fed32155", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### 2.4. NUMERICAL METHODS", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 26, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "079506c1-43c8-423d-93f5-bbb8845c0818": {"__data__": {"id_": "079506c1-43c8-423d-93f5-bbb8845c0818", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.8, para 2](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "885b632a-e839-4228-ac70-2c4960b03b99", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.8, para 2](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "cc8effbc113f8513864cad39f8ecec305f955baa208e212147ef9e9af1ebf3a1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The model was implemented in C++ and uses a freely available implicit solver (SUNDIALS IDA 2.3.0; Hindmarsh et al., 2005) as a physics engine. The neuromuscular system was solved by Euler integration (with a 1 ms step); the Sundials physics solver used adaptive time steps with a base relative error tolerance of 10^-12 and absolute spatial tolerances of 10^-9 for the coordinates and 10^-5 for rod angles. For less resistive media C\\_|| \\le 27.3 \\times 10^-6  kg \\cdot s^-1 or C\\_\\perp \\le 51.2 \\times 10^-6  kg \\cdot s^-1, all tolerances were reduced by a factor of 10.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 571, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8c9c74f3-e65c-449d-a0af-0e0b0a44ee95": {"__data__": {"id_": "8c9c74f3-e65c-449d-a0af-0e0b0a44ee95", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.8, para 3](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f21e9989-b7c4-4c99-b218-12d21315b9db", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.8, para 3](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "0e71ce6f69b0c9a13061b92699032db28c87707d701744e73a105f7fef967f9b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## 3. RESULTS", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 13, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c47862d6-58b0-460f-82d6-148ddd8f3e06": {"__data__": {"id_": "c47862d6-58b0-460f-82d6-148ddd8f3e06", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.8, para 4](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "df258abe-e834-4c04-bd75-62f0488c2da2", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.8, para 4](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "fdb1c29f40ac182403c1d9f1ec26b8ee5c859c297a1a14e84a922404c0fe45b1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Having developed our neuromechanical model of *C. elegans* forward locomotion, the first key question is to what extent this model can capture swimming and crawling behaviors in different physical environments. In particular, one would expect that placing model worms in different virtual environments would result in different motor behaviors, but it is not clear *a priori* what range of motor behaviors can be obtained in this way. For example, what would a model that was optimized for replicating crawling behavior yield when placed in virtual water, or vice versa? And are two different parameter sets needed to generate crawling and swimming patterns? If so, some form of neural or muscular modulation mechanism may need to be conjectured to account for parameter changes.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 779, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "03575db7-3809-4fa6-ac5f-7d7de0fe4dd1": {"__data__": {"id_": "03575db7-3809-4fa6-ac5f-7d7de0fe4dd1", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.8, para 5](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9ceb1d6b-e175-41c5-98f5-4876251917ef", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.8, para 5](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "40c84e56af4d21b2d7a3307cfe18151045560ac735cf0b67059b26b969473805", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### 3.1. A SINGLE NEURAL MECHANISM ACCOUNTS FOR SWIMMING AND CRAWLING", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 69, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f523b086-8d44-4980-b8f8-49737d4e20d3": {"__data__": {"id_": "f523b086-8d44-4980-b8f8-49737d4e20d3", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.8, para 6](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "dc9fe61b-4d83-416b-ac29-12a69e5a781b", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.8, para 6](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "8706c9223bfa24e7199d4fb37540694b65082c0faa6b296cdd77c8c502bd8a17", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We find that a single model with a single set of parameters is able to reproduce both crawling and swimming with realistic undulation frequencies and waveforms (**Figures 4B** and **5A,C**; Movie S2 in Supplementary Material). Crucially, this is accomplished without any explicit modulatory mechanism (beyond proprioceptive feedback). Indeed, the only *changes* necessary to obtain these different behaviors are to the effective drag coefficients that define the model environment. We conclude that a single, fixed neural circuit is sufficient to model both behaviors, without recourse to neuromodulation, additional sensory input to head neurons, or variations in proprioceptive fields or properties.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 701, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2a9766ab-ad61-4aa9-a51e-2376749d74b7": {"__data__": {"id_": "2a9766ab-ad61-4aa9-a51e-2376749d74b7", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.8, para 7](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "844ca85e-321c-49d1-aeff-9f0b60b2bd4a", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.8, para 7](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "b4bf487dde13eb5ffc2f2191627b6688b100ecdfe745fe9039a8305fe5855a5b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "How does the same model generate both crawling and swimming patterns? To understand the common oscillatory mechanism underpinning these behaviors, it is helpful to follow an oscillation in a single neural unit connected to a section of body. Consider such a system that is initialized with both DB and VB states off, with the body shape completely straight. Switching the AVB input on drives VB above its activation threshold, and causes the ventral muscles to contract, stretching the dorsal side. At some point the dorsal stretch will be sufficient to activate DB and VD. Ventral inhibition resets VB (switching it off). At this stage bending will reverse, with the dorsal side contracting and the ventral side stretching, until the dorsal contraction drops the input to DB below the deactivation threshold, turning it off and indirectly releasing VB from inhibition. Note the importance of dorso-ventral asymmetry that allows the ventral side to be activated first and to de-activate only in response to ventral inhibition (with AVB on).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1040, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "41615de7-b447-41c6-a83b-b7b8062956c8": {"__data__": {"id_": "41615de7-b447-41c6-a83b-b7b8062956c8", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.8, para 8](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "069b9c9a-e105-4a23-819f-58d10853d672", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.8, para 8](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "d80bc1382cb02140fba89db868f3a1a9786528c03f637e6dca5cb6c17f75fcd1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "For the oscillation to propagate down the length of the body, some form of coupling among units is required. In our model, the neural units are indirectly coupled through the shape of the body (i.e., through posterior stretch receptors) and through the physical properties of the body and environment. The relative importance of these contributions depends on the properties of the medium (Boyle, 2010; Fang-Yen et al., 2010). First let us consider highly resistive environments, such as agar. With the body initialized along a straight line, as above, all VB neurons are on. During forward motion, the worm's body exhibits a decreasing undulation amplitude from head to tail. Accordingly, in the model, ventral muscles exert a contractile force with a decreasing gradient toward the tail. Thus the head is the most strongly activated and will bend first, pulling the worm forward slightly and allowing more of the body to bend. Sufficient bending of the head will eventually activate dorsal neurons and bending will reverse. It is the delay in bending (rather than in actuation) imposed by strong lateral drag forces that gives rise to the crawling wavelength. In less resistive media such as water, neural units cannot rely on physical coupling via the environment for entrainment, so the synchronizing effect of non-local stretch receptor signals must determine the spatial wavelength.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1388, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5a356e2c-8c1e-4f33-abab-108080f4a61a": {"__data__": {"id_": "5a356e2c-8c1e-4f33-abab-108080f4a61a", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.8, para 9](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "490da90a-26db-4fe5-8a19-510737ef46c6", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.8, para 9](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "34f76531b4d1a242e7441dd3d2977fe30d90767fd64bbfd4137765cc43250dc4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "To test the above reasoning we used the model to experiment with variable length stretch receptor fields in B-class motor neurons. Comparison of **Figure 6** to **Figure 4D** confirms that forward crawling (but not swimming) can be generated by a model with exclusively local proprioceptive feedback. Thus the model predicts that shortening the distal processes of B-class neurons through laser axotomy or mutation would lead to a locomotion defect that is significantly more pronounced in less resistive media like water.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 522, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "768e6493-724a-4d12-acf8-a6c4924e3d48": {"__data__": {"id_": "768e6493-724a-4d12-acf8-a6c4924e3d48", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.8, para 10](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f791fe19-2d20-418b-8e3c-a07a56d1167b", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.8, para 10](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "f608c9d29766d0fec3092eeaa58e276c3a859a79c184dcc6329ecd43d401d81d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### 3.2. INCREASING FLUID VISCOSITY OR VISCOELASTICITY IS SUFFICIENT TO ACCOUNT FOR THE SWIM-CRAWL TRANSITION", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 109, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5cf31c94-fb73-4861-b713-f0ccb3433678": {"__data__": {"id_": "5cf31c94-fb73-4861-b713-f0ccb3433678", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.8, para 11](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "52c2c33c-9133-4557-8214-2fc0e777995b", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.8, para 11](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "5f922ad5c7f341f79651ff0f4dae03d0bed76598054aeee9b580f5bfe0904e26", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Having developed a model that can swim and crawl, we performed simulations of the same model in a range of additional model environments and compared our results with experimental data. In the model, fluid environments are represented by local drag coefficients resisting motion tangential (C\\_||) and normal (C\\_\\perp) to the local body surface. In Newtonian environments, the ratio K = C\\_\\perp/C\\_|| is constant. More general, viscoelastic environments (like gels), are also well described by a pair of drag coefficients, but the ratio K can vary. We tested our model in a range of viscous and viscoelastic model environments.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 629, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7c2c0da4-f26a-4e6f-a643-212cd16be921": {"__data__": {"id_": "7c2c0da4-f26a-4e6f-a643-212cd16be921", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.8, para 12](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b0237be2-9f1b-4510-979e-4163094e559f", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.8, para 12](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "c4beb00767795cade34c36f56197d3b05cf485ac3eae5422da106df61ff37268", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "First, we sought to test the model's swim-crawl transition. This transition has been experimentally mapped in gelatin solutions with different concentrations (Berri et al., 2009), and is characterized by a smooth and monotonic frequency-wavelength relation (**Figure 4A**). Our model is also capable of intermediate behaviors (**Figures 4D** and **5**; Movie S2 in Supplementary Material) and follows a similar frequency-wavelength relation (**Figure 4B**) across a large class of intermediate environments, qualitatively reproducing the smooth swim-crawl transition. Thus, we find that the entire swim-crawl transition can be modeled by a single (fixed parameter) neuromechanical system that is being modulated purely by modifying the drag coefficients of the fluid environment.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 779, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "165d71fa-ec94-411b-b3be-a51a67d51786": {"__data__": {"id_": "165d71fa-ec94-411b-b3be-a51a67d51786", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.8, para 13](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f46d5942-9e5b-4fcb-a188-4bda91d1bdc9", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.8, para 13](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "ba5f7f27b798b1e25956ec292b69b364d600440bb99dbc9dbd8e1e9f2e32c280", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "A waveform modulation similar to that reported by Berri et al. (2009) for viscoelastic media was consequently reported also for increasing viscosities (Fang-Yen et al., 2010; Shen and Arratia,", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 192, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "aeb054ca-e044-4494-bfdc-4473293f67f2": {"__data__": {"id_": "aeb054ca-e044-4494-bfdc-4473293f67f2", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.8, para 14](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2cd22bab-e068-42b8-93f0-df52b0b5168d", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.8, para 14](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "b2612e9a004777ce199d3644276efc6900a00ef1dfa5e5f5253c9f7400b9b6b1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Frontiers in Computational Neuroscience | www.frontiersin.org | March 2012 | Volume 6 | Article 10 | **8**", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 106, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c3928e3c-1dd7-40df-ac94-9ec69848d1ea": {"__data__": {"id_": "c3928e3c-1dd7-40df-ac94-9ec69848d1ea", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.9, para 0](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "db4e3240-9235-4587-9637-d1981c5cd5ab", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.9, para 0](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "4f79d6086c55eafdad8060d1371cf7df3bf88798d6eb39a122bcb2fe77386fb2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Boyle et al.\nNeuromechanical model of *C. elegans* locomotion", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 61, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "964667da-3581-4147-adbd-0fb76fbb0811": {"__data__": {"id_": "964667da-3581-4147-adbd-0fb76fbb0811", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.9, para 1](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "13e9345e-b944-4876-8481-f22b53458d85", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.9, para 1](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "ee3a8b84249661131790d48c81b2b391734deb0556802287af9d9c76a9b1c778", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "![Figure 4: Swim-crawl transition analysis. (A) Experimental data. (B) Model results. (C) Parameter space of drag coefficients. (D) Curvature contour plots.](figure_4_placeholder)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 179, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "31c9d0a3-0731-4d85-877b-e91120a6af3a": {"__data__": {"id_": "31c9d0a3-0731-4d85-877b-e91120a6af3a", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.9, para 2](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8402b55d-be42-44e2-8c5b-6dd1f7b85edf", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.9, para 2](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "ca53b06a41568d87b484b1fdd8f8781551747a9ff8bb6f9901074f76bc1bfe65", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**FIGURE 4 | (A)** Experimentally observed transition from swimming to crawling, from Berri et al. (2009), showing locomotion in gelatin (circles; color bar indicates percent gelatin concentrations) and agar (black triangles). **(B)** The swim-crawl transition. The model reproduces the smooth regulation of undulation frequencies and wavelengths with good quantitative agreement \\[colors as in **(C)**]. Selected points used in **(D)** are highlighted with pink circles. Wave properties are extracted as described in Berri et al. (2009). **(C)** Values of C\\_|| and C\\_\\perp used to evaluate the swim-crawl transition (1.5 \\le K \\le 40). Colors denote the product C\\_|| \\times C\\_\\perp, ranging from light yellow (virtual water) to dark red (virtual agar). Newtonian environments (K = 1.5) are marked with blue crosses, as are the corresponding points in **(B)**. A few combinations of drag coefficients yielded uncoordinated behavior (black dots), and were omitted from **(B)**. **(D)** Contour plots for locomotion in (from top) water, two intermediate environments and agar. The plots show the local curvature (color) along the worm (vertical axis) and in time (horizontal axis).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1183, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6f31239a-f0a0-4d42-a6f1-9ef8c35ec461": {"__data__": {"id_": "6f31239a-f0a0-4d42-a6f1-9ef8c35ec461", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.9, para 3](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "241c8215-354b-42e2-808d-b42d1e451a22", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.9, para 3](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "4bca50b87592019ce57bfe5706209765956faf902f0a079680eb82af86b1d37f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "2011\\). It is therefore natural to ask whether the model could also generate a swim-crawl transition in Newtonian media of increasing viscosity. **Figures 4B,C** confirm that, in the model, Newtonian media can modulate the waveform and kinematics of the locomotion, similarly to the modulation observed in viscoelastic media.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 325, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7b1f6178-6839-4605-bc30-9bd4de40f99f": {"__data__": {"id_": "7b1f6178-6839-4605-bc30-9bd4de40f99f", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.9, para 4](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "862aa4cc-71d5-4488-86cd-19b670944501", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.9, para 4](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "b7d0bf4a42506b62e1ce2200d8171a965580a1c1579e662252c6601c712878e1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Combined, these results suggest that it is the resistivity of the medium, rather than the ratio of drag coefficients that modulates the waveform and kinematics of locomotion. Such a conclusion would be consistent with our previous observation (Berri et al., 2009) that the worm can generate crawling-like undulations even in isotropic environments with K \\approx 1.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 365, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "92c550c9-e140-41db-af6a-9bd6272168a1": {"__data__": {"id_": "92c550c9-e140-41db-af6a-9bd6272168a1", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.9, para 5](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a3a4b6f9-58b3-44c4-b204-7810029711ad", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.9, para 5](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "197ba27476746c058bb59b5255140e63f5666809e60fc106057131c15b37aec3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### 3.3. THE MODEL REPRODUCES OBSERVED LOCOMOTION DYNAMICS IN ARTIFICIAL DIRT ENVIRONMENTS", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 90, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ae51ab4c-70b6-4eb3-8ccb-dd9ce158bae1": {"__data__": {"id_": "ae51ab4c-70b6-4eb3-8ccb-dd9ce158bae1", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.9, para 6](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "eca4a906-8262-432c-ad20-25943c02b983", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.9, para 6](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "97b1603535e89558afe833b409e0e016daff8b5fbce674dae80ec81c663fab37", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "While in the lab *C. elegans* is studied mostly on agar environments, its natural habitat is far more heterogeneous and likely to include many solid obstacles. Studying locomotion in complex environments can inform our understanding of the worm's behavior in more natural environments. Furthermore, studying", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 307, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0f74a2ef-c02c-45b2-b0b9-0efa9c596783": {"__data__": {"id_": "0f74a2ef-c02c-45b2-b0b9-0efa9c596783", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.9, para 7](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0b945698-aae6-40d8-9492-648bbdae9039", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.9, para 7](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "8f428ead33aefc3fbb864b40d005ac9264f3ddf6ace3cb52a657a6660cf75c86", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Frontiers in Computational Neuroscience | www.frontiersin.org | March 2012 | Volume 6 | Article 10 | **9**", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 106, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a2d592d7-65c0-451c-bdd5-29e43f5fe87d": {"__data__": {"id_": "a2d592d7-65c0-451c-bdd5-29e43f5fe87d", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.10, para 0](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a0a9df15-c908-45b4-a4d7-b32bd1e83b7f", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.10, para 0](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "04fd127c2e8f16db04670695d43424cb9cf6694c9268ccb1f671ae13389f5a64", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Boyle et al. | Neuromechanical model of C. elegans locomotion", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 61, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "eb48f28c-5eae-4dc4-bf05-995ec34b9c4c": {"__data__": {"id_": "eb48f28c-5eae-4dc4-bf05-995ec34b9c4c", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.10, para 1](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6233413a-81e4-40e2-b013-4571d9d546f9", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.10, para 1](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "fa6584797c8eb011d35e11cb7c43bbe9424db228ed35eb553c17be705c5faf08", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "the model yields crawling behavior in the hexagonal post configuration (Movies S3\u2013S5 in Supplementary Material; Lockery et al., 2008) and swimming like motion in the cubic configuration (Movie S6 in Supplementary Material; Park et al., 2008).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 242, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "08e63343-2bc8-4b84-b266-dafe83878a48": {"__data__": {"id_": "08e63343-2bc8-4b84-b266-dafe83878a48", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.10, para 2](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "eaf5ffd7-ef96-420d-940f-76ee5d37ffb5", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.10, para 2](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "24c328bf004b1451b177828dbfff725c3995e42486805e26b11c80f4f1edc8b8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "To investigate whether the difference in behavior can be attributed to the layout of the posts or increased resistance, we performed simulations with variable post sizes and inter-post separations; with either water- or agar-filled chambers; and with or without an effective ceiling (Lockery et al., 2008). We found that both the post layout and the properties of the filler medium can affect the locomotion behavior. When the filler medium has low resistance (i.e., water) the undulation frequency is high, but the amplitude and wavelength depend on the post layout (Movies S7\u2013S9 in Supplementary Material). In contrast, when the filler medium is highly resistive (i.e., agar) the behavior tends to be crawling-like. In cases where the post layout is roughly compatible with crawling, the locomotion waveform adapts to these constraints (Movie S10 in Supplementary Material). However, when the layout is not compatible, the worm essentially becomes obstacles (Movie S11 in Supplementary Material).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 998, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ecac4dda-69d2-4f75-a330-d4e62ce4511a": {"__data__": {"id_": "ecac4dda-69d2-4f75-a330-d4e62ce4511a", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.10, para 3](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "aac24089-7bcb-4f47-b0ad-d88cf5db0441", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.10, para 3](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "6b1932672018ede6bdc5e9338885c6cf7b3cbcbb3c9d07f259666d7d9b6444fc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## 3.4. THE MODEL REPRODUCES CONTACT FORCES", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 43, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1abd5d3a-5f15-470e-8c33-cb3ed27cb456": {"__data__": {"id_": "1abd5d3a-5f15-470e-8c33-cb3ed27cb456", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.10, para 4](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2d567310-7dea-435f-8727-90a202df8059", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.10, para 4](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "03dbef630edb133fd79fc6d0c9b76ef65f57baa2d1ad35c85fd6b312850aab7f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "One advantage of a fully integrated neuromechanical model is its physical grounding that can be tested against measurable properties or even actual force measurements. Indeed, the force exerted by C. elegans as it moves against a microfluidic pillar was recently reported to be 2.5 \u00b1 2.5 \u03bcN (Doll et al., 2009). Recreating the same setup in our model, we obtain a value of F = 0.84 \u00b1 0.22 \u03bcN for the mean peak contact force when the worm touches a pillar in model simulations. This value is totally consistent with the experimentally reported value, which is particularly remarkable when considering that parameters in our physical model were chosen purely on the basis of estimates of environmental properties and behavioral observations (Sauvage, 2007).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 755, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c474022e-67a6-4056-8323-78e36361c225": {"__data__": {"id_": "c474022e-67a6-4056-8323-78e36361c225", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.10, para 5](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9ff7aee5-94ce-48e7-ae3b-02075f141b96", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.10, para 5](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "26de6fdcaea3a735af2e5b7be1dc624057a45600058a8dd6288ed3e41010eb62", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## 3.5. BISTABLE NEUROMUSCULAR CONTROL IS ESSENTIAL FOR SUSTAINING PROPRIOCEPTIVELY DRIVEN UNDULATIONS ACROSS THE RANGE OF OBSERVED BEHAVIORS", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 141, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4c0cb742-541e-469c-9526-f52519786654": {"__data__": {"id_": "4c0cb742-541e-469c-9526-f52519786654", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.10, para 6](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "03afb4c5-00e5-4a4c-a8ff-10cf78eb59cf", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.10, para 6](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "85239266bd35296cc7656b510ebb20be9b15a8183b60b3bc30ee59c5f9263b30", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Previous models of locomotion typically assumed graded potential neurons (Niebur and Erd\u0151s, 1991; Rakowski et al., 2006; Bryden and Cohen, 2008), in line with available data at the time (Goodman et al., 1998; Nickel et al., 2002; Francis et al., 2003; O'Hagan et al., 2005). In fact, the richness of neurodynamics has only recently come to light (Mathews et al., 2003; Suzuki et al., 2003; Mellem et al., 2008). In particular, the finding of bistable motoneurons with discrete membrane potential states (Mellem et al., 2008) suggests that motor control circuits may be modeled as a network of binary motoneurons with hysteresis.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 628, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "927b567b-88bb-4307-a229-54f95467cfb8": {"__data__": {"id_": "927b567b-88bb-4307-a229-54f95467cfb8", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.10, para 7](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d5566195-1ec2-458d-8fe1-3df38a366143", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.10, para 7](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "e7a25758fb08436ed155b0c8e64d30ba837b2778ac0765489098517eb3c05dd2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Bistability introduces memory into the system, allowing neurons to respond differently to inputs when the body is bending one way or the other. This allows the system to generate robust oscillations with a broad range of frequencies (here, \u22480.5\u20132 Hz) that depend on the physical load. Indeed, in the absence of such bistability (or explicit modulation of the neuronal properties), one would expect oscillations to occur only over a relatively narrow range, determined by the interplay between relevant neuronal time constants.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 526, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3d1c9d6a-9e8a-4c84-9052-e3d5ab6db186": {"__data__": {"id_": "3d1c9d6a-9e8a-4c84-9052-e3d5ab6db186", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.10, para 8](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4913da1b-ed71-4b2a-b8d1-4abdd39acf6f", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.10, para 8](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "ab59e2fe9d974ea45b212cc9ae30c660388d2d129a529afac83c132c79977407", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|**FIGURE 5 \\| Selected stills showing behavior of the integrated model in, virtual water (A), intermediate gelatin (B), and agar (C).** The corresponding movie clips are available in Supporting Information Movie S2 in Supplementary Material. The time in seconds for each frame is given in the lower left corner. Note the different time intervals between stills in (A) versus (B) and (C).|||\n|-|-|-|\n|**A**|**B**|**C**|\n|0|0|0|\n|\\[Worm body curve illustration]|\\[Worm body curve illustration]|\\[Worm body curve illustration]|\n|0.03|0.2|0.2|\n|\\[Worm body curve illustration]|\\[Worm body curve illustration]|\\[Worm body curve illustration]|\n|0.16|0.4|0.4|\n|\\[Worm body curve illustration]|\\[Worm body curve illustration]|\\[Worm body curve illustration]|\n|0.22|0.6|0.6|\n|\\[Worm body curve illustration]|\\[Worm body curve illustration]|\\[Worm body curve illustration]|\n|0.32|0.8|0.8|\n|\\[Worm body curve illustration]|\\[Worm body curve illustration]|\\[Worm body curve illustration]|\n|0.4|1|1|\n|\\[Worm body curve illustration]|\\[Worm body curve illustration]|\\[Worm body curve illustration]|\n|0.48|1.2|1.2|\n|\\[Worm body curve illustration]|\\[Worm body curve illustration]|\\[Worm body curve illustration]|\n|0.56|1.4|1.4|\n|\\[Worm body curve illustration]|\\[Worm body curve illustration]|\\[Worm body curve illustration]|\n|0.64|1.6|1.6|\n|\\[Worm body curve illustration]|\\[Worm body curve illustration]|\\[Worm body curve illustration]|\n|0.72|1.8|1.8|\n|\\[Worm body curve illustration]|\\[Worm body curve illustration]|\\[Worm body curve illustration]|", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1537, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d43debb3-32cd-4d84-b248-6464ca842f39": {"__data__": {"id_": "d43debb3-32cd-4d84-b248-6464ca842f39", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.10, para 9](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a34da91d-c0f6-49c9-bc96-62ef49b0b288", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.10, para 9](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "b420112b9d701f1778a27203e19668f71a93f4487cd0e5162934f23c886bab1a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Frontiers in Computational Neuroscience | www.frontiersin.org | March 2012 | Volume 6 | Article 10 | 10", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 103, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9c359ec4-3a14-470e-b7a0-1b6f04e48be6": {"__data__": {"id_": "9c359ec4-3a14-470e-b7a0-1b6f04e48be6", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.11, para 1](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cc6b9917-0184-481f-be2c-fb930a3bfcc7", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.11, para 1](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "46934d25a39f1bc3e88aef8e0956d968eda569915b9009156128705a96667676", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "![Curvature plots showing the effect of eliminating posterior stretch receptor input such that feedback is from local segments only. (A) On virtual agar, model worms still propagate coordinated waves from head to tail. (B) In contrast, locomotion in water is highly uncoordinated.](image_description_1)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 302, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "21566616-fb9f-4f85-af8c-84742d1aaee7": {"__data__": {"id_": "21566616-fb9f-4f85-af8c-84742d1aaee7", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.11, para 2](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3e5984aa-c4ad-4729-9970-f2546f0d5661", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.11, para 2](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "af8ff262b6bf5827996bbb568c88edff737753a9adb7151ad31012439fd2a647", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**FIGURE 6 | Curvature plots showing the effect of eliminating posterior stretch receptor input such that feedback is from local segments only. (A)** On virtual agar, model worms still propagate coordinated waves from head to tail. **(B)** In contrast, locomotion in water is highly uncoordinated.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 297, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3ba29897-6625-4e8f-b221-b7fee327282d": {"__data__": {"id_": "3ba29897-6625-4e8f-b221-b7fee327282d", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.11, para 3](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "43209ab7-4ed4-40b8-b7d2-a73a9dad6955", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.11, para 3](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "fb1cbcbf44b55cf017f2a0835899998b05277dc265eab8138e95a10825af8bbc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "![Dynamics of binary (A) and continuous (B) model B-class neurons. Note the different thresholds for activation and deactivation (arrows).](image_description_2)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 160, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5bdfbdf7-d24e-427f-9e3e-450a69f35392": {"__data__": {"id_": "5bdfbdf7-d24e-427f-9e3e-450a69f35392", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.11, para 4](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e93080e6-ffc6-45dd-b7b0-511b2b07d3ae", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.11, para 4](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "991479e35aa80d5ae12c2c50558f7e16f5b499a1aa98fd05453c6a507cfc5fd5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**FIGURE 7 | Dynamics of binary (A) and continuous (B) model B-class neurons.** Note the different thresholds for activation and deactivation (arrows).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 151, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "84703f3f-c590-4398-8e56-f382c4c82876": {"__data__": {"id_": "84703f3f-c590-4398-8e56-f382c4c82876", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.11, para 5](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7aef1d1e-b7e2-4775-9161-9a8ac105cdac", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.11, para 5](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "5c072f990522abba11dfe813218f92a38965e9c53a1fabe84a2fd83117bc5c11", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In our model bistability is implemented by modeling B-class neurons as binary entities with bistable activation functions (see **Figure 7**). This simplification approximates the behavior of RMD neurons as reported in Mellem et al. (2008). The strong non-linearity imposed by binary threshold elements (even without bistability) turns the B-neurons into on-off elements and ensures on-off switching of inputs to the muscles, and hence anti-phase (dorso-ventral) muscle contractions that are entrained to the neurons. Interestingly, previous models of locomotion have introduced non-linearities elsewhere in the locomotion circuit. In the case of Bryden and Cohen (2008) for example, stretch receptor conductances have strong non-linearity that effectively leads to \"on-off\" neuronal states, even though the underlying equations were of a graded potential neuron. The introduction of bistability into the stretch receptor conductances, or indeed into any of a number of components of the model, may lead to similar network dynamics that can robustly adapt to a range of physical environments.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1091, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "af8598fa-4041-4ff7-923e-391e99405986": {"__data__": {"id_": "af8598fa-4041-4ff7-923e-391e99405986", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.11, para 6](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "58271c7a-1c5f-4db0-b289-6991e023bfaf", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.11, para 6](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "beb8df5500d9a66047bf81472cd547bbc18c03ce1487b54117c418c8e9ff44ba", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### 3.6. BISTABLE NEURAL DYNAMICS ARE CONSISTENT WITH RECENT RECORDINGS OF NMJ CURRENTS", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 87, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b1996b28-499c-4d4c-a167-00de07cb0a91": {"__data__": {"id_": "b1996b28-499c-4d4c-a167-00de07cb0a91", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.11, para 7](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e8f7d243-1d77-47f7-9213-1e46e6433faf", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.11, para 7](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "54fab1658a12422ae02a5a3c6f9e726bacd1a907b7614398d9bdcfbaf1704997", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "While the relative simplicity of the binary model makes it preferable to use for most of our simulations, certain questions remain outside its scope. Specifically, the simplified dynamics of the binary neurons, with discrete on and off states, makes it impossible to evaluate their behavior against electrophysiological data in a meaningful way. A recent publication by Liu et al. (2009) provides the first characterization of the *C. elegans* body wall neuromuscular junction (NMJ) response to optogenetic activation and inhibition of B-class neurons.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 552, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d64273ed-c8fd-4ce1-8462-730ec0be95e8": {"__data__": {"id_": "d64273ed-c8fd-4ce1-8462-730ec0be95e8", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.11, para 8](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "425d8b77-55ea-4041-ae63-9a41dece6d1e", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.11, para 8](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "4cec9494874f7f7996aee4d496c5706bc4e984d8508107e3fd4173a859bcd3be", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In their experiments, Liu et al. used channelrhodopsin, a light activated depolarizing ion channel, to stimulate the presynaptic B-class neuron with light of increasing intensity, and recording the response current in the muscle cells. They found that the postsynaptic current increases smoothly as shown in **Figure 8A**. Liu et al. also used halorhodopsin, a light activated hyperpolarizing ion channel, to inhibit the presynaptic neuron, finding that the postsynaptic current is reduced. Looking at these results, the obvious interpretation is that the cholinergic motor neurons exhibit tonic, graded release of neurotransmitter at resting membrane potential that can be up- and down-regulated by membrane potential. This elegant result is an important contribution to understanding (and modeling of) this and other neural circuits in *C. elegans*. Moreover, the results might be taken to suggest that the motor neuron membrane dynamics are similarly graded. Indeed, had the neurons fired classical all-or-nothing action potentials then one might expect the postsynaptic currents to be similarly binary, or at least strongly non-linear. It might appear, therefore, that the", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1176, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "67821d73-51a6-4854-9cfa-3b4d72ce0cb4": {"__data__": {"id_": "67821d73-51a6-4854-9cfa-3b4d72ce0cb4", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.11, para 9](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b5c60400-b90d-4773-9617-2c25aaa4b2aa", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.11, para 9](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "5318f76fff6e21d40abcc714465eff04d02b9ea684d260e92559945063beb655", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Frontiers in Computational Neuroscience | www.frontiersin.org | March 2012 | Volume 6 | Article 10 | **11**", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 107, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "69fe81c2-6083-49d9-b8f1-c0e9c487efed": {"__data__": {"id_": "69fe81c2-6083-49d9-b8f1-c0e9c487efed", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.12, para 0](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "395cd501-9386-4285-9145-92432f4187d3", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.12, para 0](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "bf7a1c9ad465ffdaa8d25e83433f300ed7b4c3d921f01c1267a80477fc72ab21", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Boyle et al.                                                                                                    Neuromecanical model of C. elegans locomotion", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 157, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "99fbbd3e-df6b-4f07-967d-d095ad3f7148": {"__data__": {"id_": "99fbbd3e-df6b-4f07-967d-d095ad3f7148", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.12, para 1](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b5a55a03-8b49-48e5-919b-ba9adcd98787", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.12, para 1](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "5628c3479f1a77a277053bc525a2ce6d7cd104bb8126a364445a594f2e446825", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Panel A|Light Intensity (mW/mm\u00b2)|Iinject (Muscle)|Iinject (Synaptic)|\n|-|-|-|-|\n||0|0.3|0.3|\n||1|0.4|0.4|\n||2|0.5|0.5|\n||3|0.6|0.65|\n||4|0.7|0.75|\n||6|0.8|0.85|\n||10|0.9|0.95|\n|||||\n|Panel B|I\\_inj (pA)|I\\_inj/I\\_inj||\n||-5|0.4||\n||0|0.5||\n||10|0.65||\n||20|0.8||\n||30|0.9||\n||45|0.95||\n|||||\n|Panel C|I\\_inj (pA)|I\\_inj/I\\_inj||\n||-30|0.05||\n||-10|0.1||\n||0|0.4||\n||10|0.85||\n||20|0.95||\n||40|1.0||", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 399, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3e95537a-cf27-4e2e-9c46-57bcdc767dcc": {"__data__": {"id_": "3e95537a-cf27-4e2e-9c46-57bcdc767dcc", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.12, para 2](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6a7eb2c3-aac9-4540-8b96-eba164ccdbad", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.12, para 2](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "b94e2d54fae8fb2d84758b9010c17a1fe6505bbd2bf35b94b0fe7d8dc245cbea", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**FIGURE 8 | Postsynaptic currents in response to excitation of motor neurons, normalized by the maximum outward current in response to light stimulus reproduced with permission from Liu et al. (2009). Symbols indicate experimental data points and the solid lines are the best single component fits. (B) Postsynaptic currents at the conductance-based model NMJ in response to depolarizing current injection to a VB motor neuron. Red squares highlight specific points for comparison with (A). (C) Postsynaptic response of the conductance-based model to hyperpolarizing and depolarizing currents. The blue circle indicates the postsynaptic current at the neuron's rest potential of either the \"on\" or \"off\" state will result in smooth modulation of the postsynaptic current.**", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 774, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fb44b660-5f31-44d9-8a23-9627cd60cefd": {"__data__": {"id_": "fb44b660-5f31-44d9-8a23-9627cd60cefd", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.12, para 3](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "695fca4b-3e31-4aed-82d1-6240ed6b2136", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.12, para 3](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "d4cd7774ddf5d59e4baec46250435c1078df2bcca74e502f2f51bb64341d419e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "findings of Liu et al. (2009) do not support the model proposed here.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 69, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8a5ce5c9-7666-407a-bac8-ea0ff8743260": {"__data__": {"id_": "8a5ce5c9-7666-407a-bac8-ea0ff8743260", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.12, para 4](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "67e03568-4f68-455c-9c7d-7b750ffed7bc", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.12, para 4](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "c3a9090b49945d61d0cfa8e49b6b7c0f4d58ba2feb4f38a157ce63acba68d4a6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "To examine this apparent inconsistency, we developed a conductance-based model of B-class neurons (see Section 2.3). Using this neural model and a simpler, rectangular body model, we were able to demonstrate reasonably realistic locomotion in water and on agar (Boyle, 2010), confirming that the locomotion mechanism presented here does not depend on the binary approximation.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 376, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "59ea3542-44e6-40c3-8ae0-b0b92b6e0535": {"__data__": {"id_": "59ea3542-44e6-40c3-8ae0-b0b92b6e0535", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.12, para 5](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6c2d3864-27ea-4ebe-9f6d-b866d999f76b", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.12, para 5](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "41a015ab6e6cbc78ad1e34701266bcdafaeddf917e66924904231865f08918ef", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Like the binary model, here too B-class neurons exhibit rapid (though not instantaneous) switching between high membrane potentials. However, the binary discrete \"on\"/\"off\" states are replaced by continuous-valued ranges of membrane potentials (Figure 7).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 255, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b3e68b44-b058-43fc-95bb-0155539a876b": {"__data__": {"id_": "b3e68b44-b058-43fc-95bb-0155539a876b", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.12, para 6](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "236d8600-f978-4d84-86db-6f40a95ee8b0", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.12, para 6](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "2f3fe6f7b2d184f13a9f21d9bc0283cad5d7a0cf167895756495864c43d5535b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Using this conductance-based model, we compared the behavior of our continuous neural model (Figure 8B) to the data (Liu et al., 2009; Figure 8A). Specifically, we compared the postsynaptic current stimulus or light intensity. We find that, despite the strongly non-linear response in the B-class model neurons, there exists good qualitative agreement with the reported experimental currents. Figure 8C shows that the postsynaptic current in the model also decreases significantly in response to presynaptic hyperpolarization, in line with the experimental finding of tonic neurotransmitter release. While this model cannot be used conclusively to infer a single model of B-class neurons (or even to rule out passive behavior of these neurons), we can conclude that the data of Liu et al. (2009) are consistent with the bistable B-class neuron dynamics.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 853, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3621675d-a749-40e4-9224-013602b9e9be": {"__data__": {"id_": "3621675d-a749-40e4-9224-013602b9e9be", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.12, para 7](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c16f69e7-ec4d-422a-bbc7-93a3942893fb", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.12, para 7](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "cc7a92a494fa2ee8a5de853885435cc9c4791f6d9e27108b1767707215b9e662", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## 3.7. THE MODEL PREDICTS A ROLE FOR GABAergic D-CLASS NEURONS IN FORWARD LOCOMOTION", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 85, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "18b9ec37-35ba-4276-b32c-2c732c6ac08b": {"__data__": {"id_": "18b9ec37-35ba-4276-b32c-2c732c6ac08b", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.12, para 8](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "02c06a00-c902-4b52-92ba-1d5a24ceebd8", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.12, para 8](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "5be174872e85af2d4494f6c0b1f195f66739409a151f71a4812904400f173fc0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In the worm's ventral cord locomotion circuit, cholinergic neurons of class B and A mediate forward and backward locomotion respectively. The only inhibition in this circuit is mediated by D-class GABAergic neurons. Individual D-class neurons receive input from both A and B-class neurons. They inhibit muscles, and in some cases also motoneurons of class D, on either side.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 374, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2477a1d9-4489-4b1f-ace4-8aeb283e087b": {"__data__": {"id_": "2477a1d9-4489-4b1f-ace4-8aeb283e087b", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.12, para 9](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9d4489df-8b4e-4f4a-9d91-8976ed025a55", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.12, para 9](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "23415946c420dba0366a1544ab2c13e0270f29ad92b528b9d53510bc671cc8e3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "and of classes A and B, on the ventral side only (Chen et al., 2006; Boyle, 2010). The connectivity diagram of these inhibitory D-class neurons suggests involvement in both forward and backward locomotion (White et al., 1986; Chen et al., 2006). The function of D-class neurons can be blocked out through mutations of genes required in the GABA pathway (McIntire et al., 1993b), by targeted killing of D-class neurons (Walthall et al., 1993) and by laser axotomy (Yanik et al., 2004), yielding essentially the same so-called *shrinker* phenotype (Hodgkin, 1983) in all cases: When touched on the head, wild type worms will back up, whereas worms without a functional GABA pathway will contract muscles along both sides of their bodies. Thus, D-class neurons are implicated in backward motion, or at least its initiation. In contrast, forward locomotion in these mutants or D-ablated worms is described either as wild type (Walthall et al., 1993; Yanik et al., 2004), or nearly wild type with a reduction in amplitude (McIntire et al., 1993b). This leads to the commonly held conclusion that D-class neurons are not essential for forward locomotion.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1148, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "56f45881-7497-4efe-b02c-92c5c112aae9": {"__data__": {"id_": "56f45881-7497-4efe-b02c-92c5c112aae9", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.12, para 10](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d660d336-e353-4323-a970-1e9f1577a86f", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.12, para 10](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "ae3c0352b42e6d33f2e0363155aeb8157c49c1dde3493597448b3a7ba36908ac", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We therefore investigated the effect of removing inhibition from our model. We find that removing all inhibition in our model leads to grossly normal crawling behavior on model agar, but a total inability to swim in water (Boyle S12 and S13 in Supplementary Material). At first sight, this model result may appear in stark contradiction to experimental data. In fact, in every case where forward locomotion of GABA pathway defective worms was reported (McIntire et al., 1993b; Walthall et al., 1993; Yanik et al., 2004), the assay was performed on agar. Our model therefore makes a novel prediction that these worms are swim-defective.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 635, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c9e72a63-749f-4d85-969a-be68ed7005f7": {"__data__": {"id_": "c9e72a63-749f-4d85-969a-be68ed7005f7", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.12, para 11](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d563b656-5079-420a-8694-7e9d30c66235", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.12, para 11](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "98769bd8c215cdb150a708a8dbf405e796e2a915d31eadb00f6346ea42139105", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Further analysis of the swim-defective model phenotype suggests that in the model, it is neural inhibition (of VB by VD neurons) that is responsible for the swim-defective phenotype. This effect is consistent with our description of the oscillation mechanism which requires inhibition of VB neurons to switch them off when the dorsal side is activated. Recall that in our model, we have introduced asymmetries in the parameters of the ventral and dorsal neurons that allow ventral (VBn) but not dorsal (DBn) neurons to switch on even when the worm is completely straight.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 571, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4f6674e4-9bfe-4b10-87db-0124671d210b": {"__data__": {"id_": "4f6674e4-9bfe-4b10-87db-0124671d210b", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.12, para 12](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2d7e9ccc-8649-4903-866b-8da2f91eee69", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.12, para 12](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "a4cc32ebfca6a1a55c8128dd1be9cf214adbe4e4c49369c696f551b0b3d63e9d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Frontiers in Computational Neuroscience                                                                                                    www.frontiersin.org                                                                                                    March 2012 | Volume 6 | Article 10 | 12", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 297, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9aff952f-7d07-4c6c-ace4-8d5ba79ddada": {"__data__": {"id_": "9aff952f-7d07-4c6c-ace4-8d5ba79ddada", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.13, para 0](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d9dd2a07-682e-45e5-9cae-f35e31e286d5", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.13, para 0](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "4ccb13da5bd37f426d9a7349bbae512c3764e50c61015d7c92b7710de570f104", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Boyle et al. Neuromechanical model of *C. elegans* locomotion", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 61, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "eeef6af2-a73d-4910-9536-b7465eb9cde8": {"__data__": {"id_": "eeef6af2-a73d-4910-9536-b7465eb9cde8", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.13, para 1](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e6b8626c-1a01-47a6-829a-65ba7ddd7872", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.13, para 1](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "1f85a9f63724d2e4eb415422c66159af3c7f352f7a7a2cb5240b0079be0a2dbf", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "During crawling, the delay imposed by the physical interactions between the body and environment allows the ventral side of the body to contract sufficiently to switch the VB neurons off, even in the absence of neural inhibition. However, during swimming, the low resistivity of water no longer allows VB to reset except via neural inhibition. Interestingly, muscle inhibition does not appear to offer an appropriate resetting mechanism in the context of a sensory feedback based oscillatory mechanism in which B-class neurons are depolarized in response to local stretch (Boyle, 2010). The role of a resetting mechanism is to ensure that when a given neuron becomes depolarized, its opposite counterpart is immediately repolarized \u2013 something that is easily achieved through direct neural inhibition. In contrast, if the opposite muscle is inhibited instead, the resulting relaxation would indirectly depolarize the opposite neuron (via stretch receptors) thus delaying, rather than accelerating, its repolarization.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1017, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "72c0ba91-b2d8-440d-8500-916be9ad6dc3": {"__data__": {"id_": "72c0ba91-b2d8-440d-8500-916be9ad6dc3", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.13, para 2](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f4b6b66c-a598-4909-bbc4-c11b9df6f29d", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.13, para 2](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "f58dd509034fcff42fe90516800517d4b52fe34ecedd73c1e51e81984415f26d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# 4. DISCUSSION", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 15, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "069e8e30-3924-4204-b66b-f19d9eb9a7f0": {"__data__": {"id_": "069e8e30-3924-4204-b66b-f19d9eb9a7f0", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.13, para 3](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3dae349d-5f8e-44fe-ae3f-69e9149dccfb", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.13, para 3](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "5a78298af698a23a5a0f19d669deb570235e3bd9c65d632cd643fb24d95c42e2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We have presented a fully integrated, biologically and physically grounded model that accounts for *C. elegans* locomotion in a variety of media ranging from water to agar, and in complex environments such as artificial dirt. The model was motivated by the recent finding that swimming, crawling, and a continuum of intermediate locomotion waveforms represent different manifestations of the same fundamental behavior in different physical environments (Berri et al., 2009; Fang-Yen et al., 2010; Boyle et al., 2011). These findings strongly suggested that a single underlying neural mechanism is at work, and posed a clear challenge to generate a model of the neural control of locomotion that is valid across more than a single environment.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 742, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0f6748e4-a035-4cd8-bac6-03bf9e4d72f6": {"__data__": {"id_": "0f6748e4-a035-4cd8-bac6-03bf9e4d72f6", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.13, para 4](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "716d098f-79aa-4f51-9b66-399cf8e1c3c0", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.13, para 4](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "402db4cd1220a67bfd2faa0f6e701a731f8607b40ca6bc50d4fe87b9a22ec294", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Mechanisms of gait modulation in other model systems can include gradual recruitment of neurons into an active pool (Li et al., 2007) and local modulation of the appropriate pattern generating circuits (Harris-Warrick, 1993). In *C. elegans*, the sparsity of motoneurons along the ventral cord of the animal appears to preclude the former possibility, suggesting that the range of observed behaviors results from the modulation of a single circuit.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 448, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d89bcdfe-4111-4fd0-90de-f70dfa6664f8": {"__data__": {"id_": "d89bcdfe-4111-4fd0-90de-f70dfa6664f8", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.13, para 5](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "68dab292-0a65-4fe1-95cd-ed601595d434", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.13, para 5](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "818330d540aa3992ed0d6a8c400ddf2799d7deec596c090f821bc4c462c5011f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Here, we have demonstrated that a model with ascending proprioceptive control is sufficient to generate most of the observed behaviors. In this model, the worm\u2019s forward locomotion requires neither central pattern generated control nor additional head circuitry. Nor does our model require any modulation of the neuronal or circuit parameters. Rather, the adaptation of the waveform in different media requires only indirect modulation via the physical response of the body to the environment. The modulation of the neural control circuit is then accomplished solely via proprioceptive integration of the different body shapes.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 627, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "76ad3e21-7a3f-4894-9bec-486dc525a445": {"__data__": {"id_": "76ad3e21-7a3f-4894-9bec-486dc525a445", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.13, para 6](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f1af8545-41e3-4b66-9b33-846082dfeebb", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.13, para 6](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "6f56de228aeee3fc1e7621046030b9e6685df294fed7626b2c3aebc652abad14", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "This novel mechanism is neurally economical and produces robust locomotion in extremely varied environments. Thus, the model here highlights the added insight that can be gained by studying the worm\u2019s locomotion nervous system in the context of its physical embodiment. Of course, the sufficiency of this circuit and circuit mechanism in no way rules out a range of other likely contributions to the locomotion system, including participation of other ventral cord motor neurons (e.g., of classes AS and VC), effects due to the largely independent head motor circuit, and indeed contributions from neuromodulation (Sawin et al., 2000). That said, this model points to the power of proprioceptive modulation in this system and predicts that the worm\u2019s forward locomotion should be robust to defects in these other circuit mechanisms.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 832, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c4992821-d4f5-4a72-8ed3-5d61036c4861": {"__data__": {"id_": "c4992821-d4f5-4a72-8ed3-5d61036c4861", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.13, para 7](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "739924ce-c804-492a-a6a7-26890d1fe402", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.13, para 7](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "a7e457e5b933c36cf74e9febda7b8ed4ac80e85fc6fc360b5458c60d40aac7ed", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Our model contains a number of essential ingredients. First, to adapt the neural activity patterns to the different media, the proprioceptive (or stretch receptor) signal must span a sufficient length of the body. Previously, the necessary extent of proprioceptive receptive fields has been considered only for crawling-like motor patterns (Niebur and Erd\u00f6s, 1991; Bryden and Cohen, 2008), but we find that our model requires integration of proprioceptive inputs over up to half a body length. Indeed, our model suggests that the length of this receptive field should be determined by the longest (i.e., swimming) wavelength of undulations. That said, B-class axons in *C. elegans* do not extend to half a body length, suggesting additional mechanisms may be at play. For example, modifications to body properties, different stretch receptor distributions and (possibly non-linear) conductances, and additional proprioceptive pathways (other than via B-neurons) may all contribute to reducing the minimum required receptive field.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1030, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a77993cc-3237-4860-a3b4-f665203e53f6": {"__data__": {"id_": "a77993cc-3237-4860-a3b4-f665203e53f6", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.13, para 8](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7aaeacab-cdc3-4eb5-b77e-2d17cf37af53", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.13, para 8](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "28d2573b385363d5367326171c1944057e643348dce5c3bc8525fcab52355a40", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Secondly, some bistability is essential in our model to support the dynamic range of undulation frequencies. In line with data on RMD neurons, we have chosen to implement such bistability via state-dependent activation and deactivation of the B-class motor neurons. In addition, some form of strong non-linearity is likely to be needed somewhere along the neuromuscular pathway to avoid muscle co-activation on the two sides of the body. In other words, for wild type worms performing forward locomotion it is reasonable to expect that when one side is contracting, the other side should relax. In fact, RMD neurons exhibit such strong non-linearities, and we conjecture that B-class neurons may exhibit similar behavior. Thus, we have implemented bistability by defining binary activation states of B-class motor neurons. To validate these assumptions against available data (Liu et al., 2009), we also presented a complementary conductance-based model of B-class neurons. The ability to fine tune the activation of motor neurons within effective bands of \u201coff\u201d and \u201con\u201d activation states may confer important advantages to the worm in richer, more realistic forms of motor pattern generation. However further experiments would be needed to ascertain whether B-class neurons exhibit any bistable behavior.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1306, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "79f6ed98-f1ac-468b-8ce9-2c436d5c4dfb": {"__data__": {"id_": "79f6ed98-f1ac-468b-8ce9-2c436d5c4dfb", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.13, para 9](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a45e2932-7c5b-48ed-82ed-1f4e4b80fc4b", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.13, para 9](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "79d6aa09fa4ad7e76b31581525a3af412e4c35cf6c1fa00bf9111848e0a7afa4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Finally, our model achieves robust proprioceptively driven pattern generation that is not reliant on independent head oscillations and can initiate locomotion from any initial worm conformation. To do so requires some asymmetry between the ventral and dorsal sides. In our model, we have chosen to instantiate that asymmetry by a lower activation threshold of the ventral side. Consequently, an additional mechanism must be invoked in order to reset the activation of the ventral side. Perhaps surprisingly, muscle inhibition by D-class neurons is not likely to perform this role (Boyle, 2010). By contrast, neural inhibition could in principle provide a suitable mechanism and would be interesting to investigate further experimentally. Specifically, if neural inhibition is responsible for VB resetting then our model predicts that GABA-null worms should experience strong defects in forward swimming, but not necessarily in crawling. Alternatively a range", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 958, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "210cb942-7863-44c6-85ed-bff8b7e250c9": {"__data__": {"id_": "210cb942-7863-44c6-85ed-bff8b7e250c9", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.13, para 10](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c3e5da86-1caa-4baf-9cad-fd0d8f379690", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.13, para 10](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "e5b53591a54fe52b53405aded384a459194c60fbfcf87209ae9f41e0040bf293", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Frontiers in Computational Neuroscience | www.frontiersin.org | March 2012 | Volume 6 | Article 10 | **13**", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 107, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "54de8e56-731f-45a3-961a-1a8dadd9fbb7": {"__data__": {"id_": "54de8e56-731f-45a3-961a-1a8dadd9fbb7", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.14, para 1](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "29e5e53d-cf6e-427e-98e2-6bd366eba3a8", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.14, para 1](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "19b21fdd211e7c671f50bfe1802c63d7e194c35e2ce8e7358a07009f849d3380", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "of other mechanisms could be involved in resetting neuronal states on one or both sides of the body. Of those, perhaps the most likely involves activity dependent changes in neuronal excitability or in neurotransmitter release (Liu et al., 2009). Other mechanisms, involving other inhibitory pathways (other than VD to VB inhibition) or even modified body properties may contribute to the predicted asymmetry.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 409, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ba712736-75a7-42c3-9cc0-57db0a9882ab": {"__data__": {"id_": "ba712736-75a7-42c3-9cc0-57db0a9882ab", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.14, para 2](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0b1597e2-47f6-4238-bbc3-248e0b69a969", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.14, para 2](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "d9111a1894ae81b383709221faae56b4f1f4811003f00dd0110c188e1e0e1176", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Our model prediction that the extent of uncoordinated locomotion is medium dependent suggests that certain defects (such as removal of inhibition) should lead to very little or no phenotype on agar and to severe defects in water. This discrepancy arises from a purely mechanical perspective, which leads to qualitatively different views of swimming and crawling (Fang-Yen et al., 2010). During crawling, mechanical load by the external medium helps to support the body shape and facilitates the generation of thrust. Thus, sufficiently minor defects in the locomotion nervous system may be masked or disguised. During swimming, external load is insufficient, suggesting that defects in mechanisms that contribute to locomotion may be more apparent.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 748, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d8c2b5a4-0400-4219-b79b-113a0a6be281": {"__data__": {"id_": "d8c2b5a4-0400-4219-b79b-113a0a6be281", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.14, para 3](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "699a8d15-2e44-4e25-8b7a-f7b3df1e771f", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.14, para 3](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "94fef9a4656c5c296e7998bac391817b6fe00688c7c2d9a266fcd4d7e103844b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The generation and propagation of sinuous undulations along the body axis is arguably one of the simpler motor behaviors orchestrated by *C. elegans*, and yet even this behavior is not yet fully understood. Our integrated neuromechanical model proposes a possible circuit mechanism that accounts for the worm\u2019s forward locomotion in a range of uniform and heterogeneous physical environments. The model highlights the ability of biological systems to exploit their physical environments in order to achieve effective and robust locomotion and sheds light on the neural mechanisms that would be needed to achieve this. Further work will build on our understanding of forward locomotion control to study more complex motor pattern generation that may require additional neural mechanisms as well as contributions from other neural subcircuits.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 841, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fb8c4332-36fa-419d-b837-d8b44189c37d": {"__data__": {"id_": "fb8c4332-36fa-419d-b837-d8b44189c37d", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.14, para 4](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2cf48c2a-212e-491e-aca7-685f059fdc95", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.14, para 4](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "ae712120c0fc47379c4a631ae19f26ed54b934736d9ffea9c875688fe8609c2e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### ACKNOWLEDGMENTS", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 19, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6631b9c1-9ab2-442c-b94c-76698320c068": {"__data__": {"id_": "6631b9c1-9ab2-442c-b94c-76698320c068", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.14, para 5](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6f9ef53c-d2c5-4505-a0be-ac8223a51c1d", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.14, para 5](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "11d210fbdbb5475e92eb5e3638fc3ac101000cb11f90218dfd2a69b0891ef212", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The authors would like to thank Ian Hope and Sophie Bamps for extensive discussions that were of great benefit to this work. Our research was made possible with funding from the EPSRC (EP/C011953/1 and EP/C011961/1) and BBSRC (BB/E008038/1).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 241, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e5e98e6b-6be3-419c-a64a-95e2f1dce92d": {"__data__": {"id_": "e5e98e6b-6be3-419c-a64a-95e2f1dce92d", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.14, para 6](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "69a922d1-b76d-409c-b720-f8cba60c1ed0", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.14, para 6](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "1f7f00b8f3dcdecc1a29fe4e87168c4d6440515eb4f53d4d0c8b9f8353e38d11", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### SUPPLEMENTARY MATERIAL", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 26, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5edcfd09-c9b5-4e1e-a433-eec254f9485b": {"__data__": {"id_": "5edcfd09-c9b5-4e1e-a433-eec254f9485b", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.14, para 7](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bd8912b2-e502-4154-a185-5d7476b42db0", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.14, para 7](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "5bdb5c535e6160846cd4c4cfd8acfd0b0870790d0053a2977995b5db9af98751", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The Movies S1\u2013S13 for this article, along with the model source code S14, can be found online at", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 96, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1b25c4a8-aac1-40d0-a502-fca04cf79863": {"__data__": {"id_": "1b25c4a8-aac1-40d0-a502-fca04cf79863", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.14, para 8](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bedbc8fb-2fc8-4f72-bfc9-73f3b8d0bf30", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.14, para 8](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "8b7236989a3b64bffd04886b19250db7be363294b1ba1785a7fa94fffef1267c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### REFERENCES", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 14, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6cbd4647-3497-4ef8-b2fb-34f189ebf4f8": {"__data__": {"id_": "6cbd4647-3497-4ef8-b2fb-34f189ebf4f8", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.14, para 9](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c08d9121-fac5-4203-a2b7-2bb72691649d", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.14, para 9](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "f5adf6855de2504c515285c0d047089c2b90a5544a59e54e007aff3b5077e95a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Berri, S., Boyle, J. 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(2010). *C. elegans Locomotion: and Integrated Approach.* Ph.D. thesis, School of Computing, University of Leeds, Leeds.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 133, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2be0a8c8-b07b-4a26-852a-4046c06c7499": {"__data__": {"id_": "2be0a8c8-b07b-4a26-852a-4046c06c7499", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.14, para 12](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b24836d0-f756-42eb-aa48-007d3182da13", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.14, para 12](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "58aaa1cda16df177495b6aef391f27b4614c87d44ebf3bd19825f30fb06122c8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Boyle, J. H., Berri, S., Tassieri, M., Hope, I. A., and Cohen, N. (2011). Gait modulation in *C. elegans*: it\u2019s not a choice, it\u2019s a reflex! *Front. Behav. Neurosci.* 5:10. doi:10.3389/fnbeh.2011.00010", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 201, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b940dde7-e38b-49c5-9806-34ae8709cf75": {"__data__": {"id_": "b940dde7-e38b-49c5-9806-34ae8709cf75", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.14, para 13](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2fbfea1e-42e8-4ae2-a087-34a499de1cc2", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.14, para 13](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "300f0b5f328f95aee3d63308347776d3195a356dc1e249a45fc6a8d15763a65a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Boyle, J. H., Bryden, J. A., and Cohen, N. (2008). \u201cAn integrated neuromechanical model of *C. elegans* forward locomotion,\u201d in *LNCS: Neural Information Processing, Part 1*, Vol. 4984, eds M. Ishikawa, K. Doya, H. Miyamoto, and T. Yamakawa (Berlin: Springer-Verlag), 37\u201347.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 274, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0f534bc8-21f5-49ce-a72b-329ff6640768": {"__data__": {"id_": "0f534bc8-21f5-49ce-a72b-329ff6640768", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.14, para 14](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b000e238-3eb8-41c2-85bc-9f2585655699", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.14, para 14](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "af0c3c334e431e58dd8a195e639a537c46bac793139d39ef4b9fb860062c8430", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Boyle, J. 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(1974). The genetics of *Caenorhabditis elegans*. *Genetics* 77, 71\u201394.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 83, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7287f1af-d1ce-4685-9c0f-220ea19b5089": {"__data__": {"id_": "7287f1af-d1ce-4685-9c0f-220ea19b5089", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.14, para 16](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "63b93d21-9436-4021-a938-8e32ebcee47a", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.14, para 16](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "38de7fb41b1bebdb5cd4799ae79020bfc5f5cb8fda24ebdd6dcea173c063fdc3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Bryden, J. 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Neurosurgery: functional regeneration after laser axotomy. *Nature* 432, 822.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 168, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f3f32fc3-39e0-4e77-b63e-a722cc3e994f": {"__data__": {"id_": "f3f32fc3-39e0-4e77-b63e-a722cc3e994f", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.15, para 27](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b2ec7ec1-405c-473d-91ff-edea196ea360", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.15, para 27](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "b41a00ad02ed8912d5c390c02bb42cf95701e30128abac5f9f024b298828bf71", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Conflict of Interest Statement:** The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 208, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a3a72eaf-13d8-4f42-9b44-b93df4fa6432": {"__data__": {"id_": "a3a72eaf-13d8-4f42-9b44-b93df4fa6432", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.15, para 28](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ca58e1f6-56ef-4e3c-b874-bb310e33123e", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.15, para 28](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "7abcac9f234d195a0578585d020bd1b782817b2541e51f9c8662b814252d89f7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "*Received: 07 October 2011; accepted: 07 February 2012; published online: 07 March 2012.*", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 89, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b7d9681f-f76d-4822-a84d-71735f470113": {"__data__": {"id_": "b7d9681f-f76d-4822-a84d-71735f470113", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.15, para 29](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "92850a76-8b14-491c-a1ac-5afffa961f20", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.15, para 29](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "b87fe67eb3676089fc47bdaaee30e60e6094a59f548e1288acf3e4fe5301ff5e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "*Citation: Boyle JH, Berri S and Cohen N (2012) Gait modulation in C. elegans: an integrated neuromechanical model. Front. Comput. Neurosci. **6**:10. doi: 10.3389/fncom.2012.00010*", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 181, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9610b4db-07e3-4ef5-9482-5625dcbdf03b": {"__data__": {"id_": "9610b4db-07e3-4ef5-9482-5625dcbdf03b", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.15, para 30](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a278e925-1e4c-4517-892c-89a2c8da185e", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.15, para 30](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "30d24d4228c0b2286ad9b7ce45ce7f7451f9f36576609d3a43327bf8d8d97d10", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "*Copyright \u00a9 2012 Boyle, Berri and Cohen. This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.*", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 298, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1525952d-4f6e-436e-ba52-70e03af939d4": {"__data__": {"id_": "1525952d-4f6e-436e-ba52-70e03af939d4", "embedding": null, "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.15, para 31](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "23cfc0ef-622d-4691-86f7-50e65a164a0f", "node_type": "4", "metadata": {"source document": "Publication: [BoyleBerriCohen2012, p.15, para 31](https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2012.00010/full)"}, "hash": "4f283bef13fdf9935d7704c9cad0740d0a427c8439301cf9d69fb04fcb7e5eee", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Frontiers in Computational Neuroscience | www.frontiersin.org | March 2012 | Volume 6 | Article 10 | **15**", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 107, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3c814e81-06eb-4a19-bd04-b6954573f28f": {"__data__": {"id_": "3c814e81-06eb-4a19-bd04-b6954573f28f", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.1, para 0](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "481cce78-71e8-4f47-9844-ded10ebcf7bb", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.1, para 0](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "f6d95545817f6e60ea4ea4dead93b10862a25e8e4f359b1d039699ce64f8566c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Article", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 9, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fc18dd87-10d9-46c8-9ddb-db36b31aac11": {"__data__": {"id_": "fc18dd87-10d9-46c8-9ddb-db36b31aac11", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.1, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "00197f90-4730-413f-9010-ac6cfbfd8e1b", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.1, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "2348b124fc836d780aa9e504e37b09e2b7865998abbfffb0197a434d0124d7d3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Neural signal propagation atlas of *Caenorhabditis elegans*", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 62, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c697b27f-cb2b-48e4-8bab-d6360834794c": {"__data__": {"id_": "c697b27f-cb2b-48e4-8bab-d6360834794c", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.1, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8d6d9a96-0750-4119-825a-7a2a0a85e93c", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.1, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "24f0453cafd75eab77df3b32a75cca90f54a8b44e594cb674a2b900b22336b86", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Francesco Randi^1,3, Anuj K. Sharma^1, Sophie Dvali^1 & Andrew M. Leifer^1,2 \u2709", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 78, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b00c9cba-f351-44c5-8db1-1978c5569174": {"__data__": {"id_": "b00c9cba-f351-44c5-8db1-1978c5569174", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.1, para 8](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d401ed47-3217-43ca-8806-a66d95c3303b", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.1, para 8](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "5c783e3dc2512cf79377d7c4605a5659b50786f04bb900ddffa5c9038364287b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Establishing how neural function emerges from network properties is a fundamental problem in neuroscience^1. Here, to better understand the relationship between the structure and the function of a nervous system, we systematically measure signal propagation in 23,433 pairs of neurons across the head of the nematode *Caenorhabditis elegans* by direct optogenetic activation and simultaneous whole-brain calcium imaging. We measure the sign (excitatory or inhibitory), strength, temporal properties and causal direction of signal propagation between these neurons to create a functional atlas. We find that signal propagation differs from model predictions that are based on anatomy. Using mutants, we show that extrasynaptic signalling not visible from anatomy contributes to this difference. We identify many instances of dense-core-vesicle-dependent signalling, including on timescales of less than a second, that evoke acute calcium transients\u2014often where no direct wired connection exists but where relevant neuropeptides and receptors are expressed. We propose that, in such cases, extrasynaptically released neuropeptides serve a similar function to that of classical neurotransmitters. Finally, our measured signal propagation atlas better predicts the neural dynamics of spontaneous activity than do models based on anatomy. We conclude that both synaptic and extrasynaptic signalling drive neural dynamics on short timescales, and that measurements of evoked signal propagation are crucial for interpreting neural function.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1533, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9d2e3cae-98b0-4f62-8753-75a57a0f3b4c": {"__data__": {"id_": "9d2e3cae-98b0-4f62-8753-75a57a0f3b4c", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.1, para 9](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "978b8b4f-4cb0-434f-be3d-acd9f78effc7", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.1, para 9](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "4a0ee61bf752a231cc17eaa0eec33fdff385b391cfb7d3234c78821bdd0fbeba", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Brain connectivity mapping is motivated by the claim that \u201cnothing defines the function of a neuron more faithfully than the nature of its inputs and outputs\u201d^2. This approach to revealing neural function drives large-scale efforts to generate connectomes\u2014anatomical maps of the synaptic contacts of the brain\u2014in a diverse set of organisms, ranging from mice^3 to *Platynereis*^4. The *C. elegans* connectome^1,5,6 is the most mature of these efforts, and has been used to reveal circuit-level mechanisms of sensorimotor processing^7,8, to constrain models of neural dynamics^9 and to make predictions of neural function^10.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 624, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "850af05a-8e2e-4319-9dcf-68dfbfbbbee1": {"__data__": {"id_": "850af05a-8e2e-4319-9dcf-68dfbfbbbee1", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.1, para 10](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b99eae8e-bc03-43dd-8179-4bbd9500b591", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.1, para 10](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "3d420a89ad7725d4ce82ecec13a97c584005efd0c1b8ce59e89d69a88ec7e798", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Anatomy, however, omits key aspects of neurons\u2019 inputs and outputs, or leaves them ambiguous: the strength and sign (excitatory or inhibitory) of a neural connection are not always evident from wiring or gene expression. Many mammalian neurons release both excitatory and inhibitory neurotransmitters, and functional measurements are thus required to disambiguate their connections^11. For example, starburst amacrine cells release both GABA (\u03b3-aminobutyric acid) and acetylcholine^12; neurons in the dorsal raphe nucleus release both serotonin and glutamate^13; and neurons in the ventral tegmental area release two or more of dopamine, GABA and glutamate^14. The timescale of neural signalling is also ambiguous from anatomy. In addition, anatomy disregards changes to neural connections from plasticity or neuromodulation; for example, in the head compass circuit in *Drosophila*^15 or in the crab stomatogastric ganglion^16, respectively. Both mechanisms serve to strengthen or to select subsets of neural connections out of a menu of possible latent circuits. Finally, anatomy ignores neural signalling that occurs outside the synapse, as explored here. These ambiguities or omissions all pose challenges for revealing neural function from anatomy.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1253, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c2e9d2b6-1349-4854-bd32-f4081c9414c0": {"__data__": {"id_": "c2e9d2b6-1349-4854-bd32-f4081c9414c0", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.1, para 11](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5eab6d19-595f-411b-b1f2-2dd2585774d4", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.1, para 11](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "8766a6a1309d7deeca7aff66ec6e7fdfb63ebf0ddc8ba2b6b86d321f9cf4cd0e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "A more direct way to probe neural function is to measure signal propagation by perturbing neural activity and measuring the responses of other neurons. Measuring signal propagation captures the strength and sign of neural connections reflecting plasticity, neuromodulation and even extrasynaptic signalling. Moreover, direct measures of signal propagation allow us to define mathematical relations that describe how the activity of an upstream neuron drives activity in a downstream neuron, including its temporal response profile. Historically, this and related perturbative approaches have been called many names (Supplementary Information), but they all stand in contrast to correlative approaches that seek to infer neural function from activity correlations alone. Correlative approaches do not directly measure causality and are limited to finding relations among only those neurons that happen to be active. Perturbative approaches measure signal propagation directly, but previous efforts have been restricted to selected circuits or subregions of the brain, and have often achieved only cell-type and not single-cell resolution^17\u201322.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1143, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6f230af8-c71f-4b6e-ba2b-b486250c13c1": {"__data__": {"id_": "6f230af8-c71f-4b6e-ba2b-b486250c13c1", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.1, para 12](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "20cfd444-917f-46a6-b5d1-7a9336948f87", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.1, para 12](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "e32ca3f878584e31f67c87a0b82f20d19985da92230a5d09ea21c9cf8d59c2a9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Here we use neural activation to measure signal propagation between neurons throughout the head of *C. elegans* at single-cell resolution. We survey 23,433 pairs of neurons\u2014the majority of the possible pairs in the head\u2014to present a systematic atlas. We show that functional measurements better predict spontaneous activity than anatomy does,", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 342, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1f8f6664-9c02-461e-9fc1-5eaf09fcf528": {"__data__": {"id_": "1f8f6664-9c02-461e-9fc1-5eaf09fcf528", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.1, para 13](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "28bac183-ef78-4a4a-a58d-0f795e278e2e", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.1, para 13](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "f2534b00cc013406f182e5d40ef134b135cebef625c2e69f38cef715d96b7401", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "^1Department of Physics, Princeton University, Princeton, NJ, USA. ^2Princeton Neurosciences Institute, Princeton University, Princeton, NJ, USA. ^3Present address: Regeneron Pharmaceuticals, Tarrytown, NY, USA. \u2709e-mail:", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 220, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ca241089-eccc-4f43-9f27-410d95af5e3c": {"__data__": {"id_": "ca241089-eccc-4f43-9f27-410d95af5e3c", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.2, para 0](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1f4a78a8-ef85-400d-b5ca-49296fa79545", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.2, para 0](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "4c3c14b18d4c7f74712e62027605db044a631210f6507e29ced0be9abb5fd11b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "a\nTunable\nlenses\n2P\nstimulation\n1P Ca2+ imaging\nspinning disk\nconfocal", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 70, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b024f248-5c02-433d-94e7-df81d54db033": {"__data__": {"id_": "b024f248-5c02-433d-94e7-df81d54db033", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.2, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4c53f30d-049d-4f49-8ccd-e1b738d362ba", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.2, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "6ee88645d75c2298745bea0548ab7472e828e0c77c9b9b42036c1de49aed7476", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "d\nStimulation:\nSABD I3 OLLL I2R AWAR I1L M3R AVDR AWBL IL2DR RMDDR CEPDR URBL I1L AWBL DB2 RMDVL RMR AVL RMDL FLPR ASHL RMDDR RIS ASHL AWAR RIVR RIG ASHL ASHR RMDR IL1DR AVDL RMDR RIVL AQR RID FLPR OLLL I2L RMDR I1R I1R RIG IL1VL M3L AIM RMDDL IL2DL RMDDR AVJL AVER IL1VL AQR OLQDR IL1DR\nADL AIM\nAIZR AQR\nASER ASGL\nASGR ASHL\nASHR AUAL\nAUAR AVAR\nAVDL AVDR\nAVEL AVER\nAVJL AVKR\nAVL AWAR\nAWBL CEPDR\nCEPVR DB2\nFLPL FLPR\nI1L I1R\nI2L I2R\nI3 I4\nI6 IL1DR\nIL1VL IL1VR\nIL2 IL2DL\nIL2DR M1\nM2L M2R\nM3L M3R\nM5 MCL\nMI NSML\nOLLL OLQDL\nOLQDR RID\nRIG RIML\nRIMR RIS\nRIVL RIVR\nRMDDL RMDDR\nRMDL RMDR\nRMDVL RMDVR\nRMEL RMER\nRMEV SAAVL\nSABD SMDDR\nURADR URBL\nVB1 VB2\nResponding neuron\n0 500 1,000 1,500 2,000\nTime (s)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 692, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "83bae3ad-7b90-4646-92f1-e0a171058275": {"__data__": {"id_": "83bae3ad-7b90-4646-92f1-e0a171058275", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.2, para 5](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f2ab90fc-d252-4347-a1d0-fea517bf7d58", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.2, para 5](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "93fa6884f0a60c55d276b4d60d220cff6a5e00d626d0ddff0aa899c64e9c7205", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "e\nAVJR (stimulated)\nAVDR (responding)\n\u0394F/F\u2080\n1.0\n0.5\n0\n-10 0 10 20 30\n-10 0 10 20 30\nSorted trials\n1\n2\n3\n4\n5\n6\n7\n8\n9\n10\n11\n12\n13\n14\n15\n16\n17\n18\n19\n20\n21\n22\n23\n24\n-10 0 10 20 30\n-10 0 10 20 30", "mimetype": "text/plain", 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trials\n1\n2\n3\n4\n5\n6\n7\n8\n9\n10\n11\n-10 0 10 20 30\n-10 0 10 20 30\nTime (s)\nTime (s)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 169, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b395eb4f-d2dd-43ce-8a8d-012962611442": {"__data__": {"id_": "b395eb4f-d2dd-43ce-8a8d-012962611442", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.2, para 8](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "48a8edba-446a-45d3-bf41-f0342ca59308", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.2, para 8](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "f1543efea4ab43a917975800d9c90348ac66d2a8f674939ac79df34a42a48d27", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "g\nSAADL (stimulated)\nOLLR (responding)\n\u0394F/F\u2080\n0.5\n0\n-10 0 10 20 30\n-10 0 10 20 30\nSorted trials\n1\n2\n3\n4\n5\n-10 0 10 20 30\n-10 0 10 20 30\nTime (s)\nTime (s)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 152, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "14041f9e-1fc5-4989-9ca8-0ab1ad1b1b35": {"__data__": {"id_": "14041f9e-1fc5-4989-9ca8-0ab1ad1b1b35", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.2, para 9](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e41652ca-9a51-4b00-a55d-748d8ffd61aa", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.2, para 9](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "fab41fd016b2c0d6b5c09d619e2943498d4407fc360ad172cf59619c83ba5ef8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Fig. 1 | Measuring neural activation and network response. a, b, Schematics of the instrument (a) and the experiment (b). c, NeuroPAL fluorophores for neural identification. d, Whole-brain cell-resolved calcium activity (GCaMP6s fluorescence normalized by noise) during stimulation of individual neurons. A stimulation was delivered once every 30 s; grey lines indicate those instances when the stimuli were delivered on-target. The targeted neurons are listed at the top. e, Paired activity of AVJR and AVDR in response to AVJR stimulation, shown as relative change (\u0394F/F\u2080). Top, mean (blue) and s.d. (shading) across trials and animals. Bottom, simultaneously recorded paired activity for individual trials (sorted by mean AVDR activity). All trials are shown that elicited activity. f, Same as e for AVER stimulation and AVAR response. g, Same as e for SAADL stimulation and OLLR response.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 892, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ca338b31-373c-4ded-bc7e-89d86ee33dbf": {"__data__": {"id_": "ca338b31-373c-4ded-bc7e-89d86ee33dbf", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.2, para 10](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9cbb7a67-21dd-447e-9da3-7c5893680b11", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.2, para 10](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "c097ce4b6d210c8adbeb3cb22f09a5e7395aac81b39f654492fe95d9a0ae5f14", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "and that peptidergic extrasynaptic signalling contributes to neural dynamics by performing a functional role similar to that of a classical neurotransmitter.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 157, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c05d7614-25c7-44f7-a473-ff95fc1fe641": {"__data__": {"id_": "c05d7614-25c7-44f7-a473-ff95fc1fe641", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.2, para 11](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "44370b82-5197-4d3d-9bef-e3ba93838e80", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.2, para 11](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "c2e9dd64ddeea63225db3a9b233060aba4b3e3ac91c2103ea540495faedbf126", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Population imaging and single-cell activation", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 48, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e5be088c-280e-4ace-8363-462e6c237368": {"__data__": {"id_": "e5be088c-280e-4ace-8363-462e6c237368", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.2, para 12](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "31f72636-321d-4637-964f-7cab51d83f35", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.2, para 12](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "78a4682b77956a7af1e1a37494c2ec558b5d4519272d436197f624e18de84c0c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "To measure signal propagation, we activated each single neuron, one at a time, through two-photon stimulation, while simultaneously recording the calcium activity of the population at cellular resolution using spinning disk confocal microscopy (Fig. 1). We recorded activity from 113 wild-type (WT)-background animals, each for up to 40 min, while stimulating a mostly randomly selected sequence of neurons one by one every 30 s. We spatially restricted our two-photon activation in three dimensions to be the size of a typical *C. elegans* neuron, to minimize off-target activation of neighbouring neurons (Extended Data Fig. 2a,c\u2013e,i,j and Supplementary Information). Animals were", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 682, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a4d0aeb3-e96f-4027-b4ad-7118f49cf36b": {"__data__": {"id_": "a4d0aeb3-e96f-4027-b4ad-7118f49cf36b", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.3, para 0](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ce705b77-39b8-46b5-8a92-008860726571", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.3, para 0](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "f87d09f3edc36662ceec4ba0c229a4b9a3d48d7d0628a985d1ea7f59eac04caa", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Article", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 9, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "22b9aac3-6d20-438d-9130-8a76368c4e54": {"__data__": {"id_": "22b9aac3-6d20-438d-9130-8a76368c4e54", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.3, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "66a22783-b106-4da5-bc5e-e4a0477f8e90", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.3, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "fc56b015f0bb88f204dc887248a1e09aaac1317f24f7310274a34d16829f0806", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "immobilized but awake, and pharyngeal pumping was visible during recordings. To overcome the challenges associated with spectral overlap between the actuator and the indicator, we used TWISP\u2014a transgenic worm for interrogating signal propagation^23, which expresses a purple-light actuator, GUR-3/PRDX-2 (refs. 24,25) and a nuclear-localized calcium indicator GCaMP6s (ref. 26) in each neuron (Fig. 1b and Extended Data Fig. 2b), along with fluorophores for neural identification from NeuroPAL (ref. 27) (Fig. 1c). Validation of the GUR-3/PRDX-2 system is discussed in the Supplementary Information (see also Extended Data Fig. 2h and Supplementary Video 1). A drug-inducible gene-expression system was used to avoid toxicity during development, resulting in animals that were viable but still significantly less active than WT animals^23 (see Methods). A stimulus duration of 0.3 s or 0.5 s was chosen to evoke modest calcium responses (Extended Data Fig. 2f), similar in amplitude to those evoked naturally by odour stimuli^28.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1029, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8f2fa6c9-2ad7-44c9-ba5b-df91d77bf9f0": {"__data__": {"id_": "8f2fa6c9-2ad7-44c9-ba5b-df91d77bf9f0", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.3, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "456d4528-958d-4366-8bce-9af363d04333", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.3, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "c9cbbb06be8e9636c5aa760035b256c703d7ce79427d86add01368acbe94070f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Many neurons exhibited calcium activity in response to the activation of one or more other neurons (Fig. 1d). A downstream neuron's response to a stimulated neuron is evidence that a signal propagated from the stimulated neuron to the downstream neuron.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 253, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3294ec58-5c90-44b4-834f-b4eb66a9f8fc": {"__data__": {"id_": "3294ec58-5c90-44b4-834f-b4eb66a9f8fc", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.3, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c10aadfa-4013-422f-9d29-b42b4568ea5b", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.3, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "2d86485a56df733e2aaaa954f89f4e5389ebd9774cd9088edde7d3112f921f72", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We highlight three examples from the motor circuit (Fig. 1e\u2013g). Stimulation of the interneuron AVJR evoked activity in AVDR (Fig. 1e). AVJ had been predicted to coordinate locomotion after egg-laying by promoting forward movements^29. The activity of AVD is associated with sensory-evoked (but not spontaneous) backward locomotion^7,8,30,31, and AVD receives chemical and electrical synaptic input from AVJ^1,6. Therefore, both wiring and our functional measurements suggest that AVJ has a role in coordinating backward locomotion, in addition to its previously described roles in egg-laying and forward locomotion.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 615, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "50ed9d77-7830-4c68-aa9a-10b47644d980": {"__data__": {"id_": "50ed9d77-7830-4c68-aa9a-10b47644d980", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.3, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1378a36c-b5c3-4dca-88c1-56b0c7b472c3", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.3, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "48d7cdd6af185a69b63e900906865778093b934195678e3623d7a2348c7fb74f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Activation of the premotor interneuron AVER evoked activity transients in AVAR (Fig. 1f). Both AVA^31\u201335 (Extended Data Fig. 2h) and AVE^31,36 are implicated in backward movement. Their activities are correlated^31, and AVE makes gap-junction and many chemical synaptic contacts with AVA^1,6.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 292, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0c66f451-1c03-4e92-8433-530b2ae05376": {"__data__": {"id_": "0c66f451-1c03-4e92-8433-530b2ae05376", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.3, para 5](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "eca5b021-132f-479e-8ebd-1d0ae7028977", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.3, para 5](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "f981596581fe0555fb891b202dc82cb3c5c4d3dee959921bc7ebbd212a51c647", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Activation of the turning-associated neuron SAADL^36 inhibited the activity of the sensory neuron OLLR. SAAD had been predicted to inhibit OLL, on the basis of gene-expression measurements^37. SAAD is cholinergic and it makes chemical synapses to OLL, which expresses an acetylcholine-gated chloride channel, LGC-47 (refs. 6,38,39). Other examples consistent with the literature are reported in Extended Data Table 1.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 417, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "300c2115-dcbf-43b4-b51d-ff1d09b12c03": {"__data__": {"id_": "300c2115-dcbf-43b4-b51d-ff1d09b12c03", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.3, para 6](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b9a81a9b-a534-4658-9059-47fed081ca12", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.3, para 6](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "71f06fd56edcf52154176e20a0c464c1e7407ea82199cea3ca4dde977968dddb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Signal propagation map", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 25, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2893e30c-244e-4610-ab19-fad7d4ffc942": {"__data__": {"id_": "2893e30c-244e-4610-ab19-fad7d4ffc942", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.3, para 7](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "93360be8-f940-4ea0-83d6-1c97a3a13619", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.3, para 7](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "3c2564e5b305ec24f4bee76227d8c5febe095160f9e7434ab2750736140173ad", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We generated a signal propagation map by aggregating downstream responses to stimulation from 113 *C. elegans* individuals (Fig. 2a). We report the mean calcium response in a 30-s time window \\langle \\Delta F / F\\_0 \\rangle\\_t averaged across trials and animals (Extended Data Fig. 3a). We imaged activity in response to stimulation for 23,433 pairs of neurons (66% of all possible pairs in the head). Measured pairs were imaged at least once, and some as many as 59 times (Extended Data Figs. 3b and 4a). This includes activity from 186 of 188 neurons in the head, or 99% of all head neurons.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 593, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a0527c73-5d89-4d30-b257-d985cf33dcb7": {"__data__": {"id_": "a0527c73-5d89-4d30-b257-d985cf33dcb7", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.3, para 8](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3639e057-e6ac-459e-bce0-28e050ecaf2a", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.3, para 8](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "f2f7c52920d0d9021c0eb1f607c218ea7d4fed10aa6be158b67edd8c92aebe43", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We developed a statistical framework, described in the Methods, to identify neuron pairs that can be deemed \u2018functionally connected\u2019 (q < 0.05; Extended Data Fig. 4b), \u2018functionally non-connected\u2019 (q\\_eq < 0.05; Extended Data Fig. 5b) or for which we lack the confidence to make either determination. The statistical framework is conservative and requires consistent and reliable responses (or non-responses) compared to an empirical null distribution, considering effect size, sample size and multiple-hypothesis testing^40 to make either determination. Many neuron pairs fail to pass either statistical test, even though they often contain neural activity that, when observed in isolation, could easily be classified as a response (for example, AVJR\u2192ASGR in Extended Data Fig. 4c).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 783, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "31ad281f-d122-4e89-9cbe-fdecd5eea42d": {"__data__": {"id_": "31ad281f-d122-4e89-9cbe-fdecd5eea42d", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.3, para 9](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "48e05e32-92ef-4951-89e0-8a175844b07d", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.3, para 9](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "31b468cb8d37fb791cebb03930d67b0a0dcb369563ec8843abaa3eefdac9500a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Our signal propagation map comprises the response amplitude and its associated q value (Fig. 2a and Extended Data Fig. 5a) and can be browsed online (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 150, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8289bce7-ffdb-4d02-944e-1a29a08e93f0": {"__data__": {"id_": "8289bce7-ffdb-4d02-944e-1a29a08e93f0", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.3, para 10](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d680d3c1-9c5d-4475-b588-abf84c1c9c50", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.3, para 10](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "9348677dcacec0960633ee2c10669b910f757d2ef54186b920fef68ad354e815", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ") through software built on the NemaNode platform^6. A total of 1,310 of the 23,433 measured neuron pairs, or 6%, pass our stringent criteria to be deemed functionally connected at q < 0.05 (Fig. 2c). Neuron pairs that are deemed functionally non-connected are reported in Extended Data Fig. 5b. Note that, in all cases, functional connections refer to \u2018effective connections\u2019 because they represent the propagation of signals over all paths in the network between the stimulated and the responding neuron, not just the direct (monosynaptic) connections between them.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 567, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "674c1706-9783-4ce8-963e-2e326f362ae7": {"__data__": {"id_": "674c1706-9783-4ce8-963e-2e326f362ae7", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.3, para 11](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "00bd6edd-d913-4881-8055-6d546f0cf732", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.3, para 11](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "21fc792983aa74a4f5133fb757e408f690bb60425cd3612b88c166d41f379195", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "*C. elegans* neuron subtypes typically consist of two bilaterally symmetric neurons, often connected by gap junctions, that have similar wiring^1 and gene expression^38, and correlated activity^41. As expected, bilaterally symmetric neurons are (eight times) more likely to be functionally connected than are pairs of neurons chosen at random (Fig. 2c).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 353, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "35351a5d-732f-4235-9a8d-d1cf8a48ddaf": {"__data__": {"id_": "35351a5d-732f-4235-9a8d-d1cf8a48ddaf", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.3, para 12](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c0134262-d306-4e81-b455-727d162e00a0", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.3, para 12](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "744dd2a85a7e5d511823b5d4485551522fdd1c6bd715660b0c0d704ebc9783a6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The balance of excitation and inhibition is important for a network\u2019s stability^42,43 but has not to our knowledge been previously measured in the worm. Our measurements indicate that 11% of q < 0.05 functional connections are inhibitory (Fig. 2d), comparable to previous estimates of around 20% of synaptic contacts in *C. elegans*^37 or around 20% of cells in the mammalian cortex^44. Our estimate is likely to be a lower bound, because we assume that we only observe inhibition in neurons that already have tonic activity.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 525, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d6137160-9768-45ca-94e9-93b5bcd7a962": {"__data__": {"id_": "d6137160-9768-45ca-94e9-93b5bcd7a962", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.3, para 13](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "78425bc0-5b67-479c-bc42-9e3ddae91204", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.3, para 13](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "ec2d1ad0d1be9b86ca71d7d0ad342659f8d9d058f8caf335948f97343ef25a5b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "As expected from anatomy, neuron pairs that had direct (monosynaptic) wired connections were more likely to be functionally connected than were neurons with only indirect or multi-hop anatomical connections. Similarly, the likelihood of functional connections decreased as the minimal path length through the anatomical network increased (Fig. 2e). Conversely, neurons that had large minimal path lengths through the anatomical network were more likely to be functionally non-connected than were neurons that had a single-hop minimal path length (Fig. 2g). We investigated how far responses to neural stimulation penetrate into the anatomical network. Functionally connected (q < 0.05) neurons were on average connected by a minimal anatomical path length of 2.1 hops (Fig. 2f), suggesting that neural signals often propagate multiple hops through the anatomical network or that neurons are also signalling through non-wired means.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 931, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "690647a1-9adf-4e91-ab1e-e4aba6a5e1d6": {"__data__": {"id_": "690647a1-9adf-4e91-ab1e-e4aba6a5e1d6", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.3, para 14](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "88213c99-45e3-42ee-a7fd-5e8ffa5ba296", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.3, para 14](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "1d4a8ddb8e6b6a40d46e41a53d0148aae53fad62dd40475a475953ae79be65cb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Most neuron pairs exhibited variability across trials and animals: downstream neurons responded to some instances of upstream stimulations but not others (Extended Data Fig. 6a); and the response\u2019s amplitude, temporal shape and even sign also varied (Extended Data Fig. 6b\u2013e). Some variability in the downstream response can be attributed to variability in the upstream neuron\u2019s response to its own stimulation, called its autoresponse. To study the variability of signal propagation excluding variability from the autoresponse, we calculated a kernel for each stimulation that evoked a downstream response. The kernel gives the activity of the downstream neuron when convolved with the activity of the upstream neuron. The kernel describes how the signal is transformed from upstream to downstream neuron for that stimulus event, including the timescales of the signal transfer (Extended Data Fig. 6b,c). We characterized the variability of each functional connection by comparing how these kernels transform a standard stimulus (Extended Data Fig. 6e). Kernels for many neuron pairs varied across trials and animals, presumably because of state- and history-dependent effects^45, including from neuromodulation^16,46, plasticity and interanimal variability in wiring and expression. As expected, kernels from one neuron pair were more similar to each other than to kernels from other pairs (Extended Data Fig. 6f).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1416, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "578a00fc-13ff-4130-b318-a015390e5be5": {"__data__": {"id_": "578a00fc-13ff-4130-b318-a015390e5be5", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.3, para 15](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "32e2d55e-1c69-4349-bfdd-dd451597a7d1", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.3, para 15](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "a470aa4e389cd2ced90186e27e112d1cd0893e3edaf6d2df836f2570b661b485", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Functional measurements differ from anatomy", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 46, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "36113354-9206-4737-8dce-481bdfc6966b": {"__data__": {"id_": "36113354-9206-4737-8dce-481bdfc6966b", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.3, para 16](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "db75995d-21f8-4d6e-8a18-fab14c0007cb", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.3, para 16](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "208ceeedd18c30ae56fe8e7c50ad9b5c560d59dbea3235da56c46d303a134272", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We observed an apparent contradiction with the wiring diagram\u2014a large fraction of neuron pairs with monosynaptic (single-hop) wired connections are deemed functionally non-connected in our", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 188, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "07505c33-b6fa-44ea-b1f7-cbac61c606cd": {"__data__": {"id_": "07505c33-b6fa-44ea-b1f7-cbac61c606cd", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.4, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8798857b-4991-4263-b7a2-3fe15713179f", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.4, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "bd5050e17024a91ad5734ef58550f08d5b7de4f4627bb8ef1c33bfe05a0ad2aa", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Fig. 2 | Signal propagation map of *C. elegans*. **a**, Mean post-stimulus neural activity \\langle \\Delta F / F\\_0 \\rangle\\_t averaged across trials and individuals. The q values report the false discovery rate (more grey is less significant). White indicates no measurement. An autoresponse is required for inclusion and is not shown (black diagonal). n = 113 animals. Neurons that were recorded but never stimulated are shown in Extended Data Fig. 5. **b**, Corresponding network graph with neurons positioned anatomically (only q < 0.05 connections). Width and transparency indicate mean response amplitude (red, excitatory; blue, inhibitory). A, anterior; D, dorsal; P, posterior; V, ventral. **c**, A bilaterally symmetric pair is more likely to have a q < 0.05 functional connection than is a pair chosen at random. **d**, Fraction of connections that are inhibitory as a function of the q-value threshold. Green indicates q < 0.05. **e**, Probability of being functionally connected (q < 0.05) given minimum anatomical path length l. **f**, Distribution of l for functionally connected pairs (blue) compared to all possible pairs (black). **g**, Probability of being functionally non-connected (q\\_eq < 0.05) given l.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1224, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e4c88948-1241-4de7-b93f-4d5986b32642": {"__data__": {"id_": "e4c88948-1241-4de7-b93f-4d5986b32642", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.4, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "92e909f0-f652-4b76-aedf-bd70409736fc", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.4, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "7b8ddece67d6975ff0ce5d317f9aca67128a492dbb2885d30e9be9d25c19fe13", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "measurements (Fig. 2g). To further compare our measurements to anatomy, we sought to better understand what responses we should expect from the wiring diagram. Anatomical features such as synapse count are properties of only the direct (monosynaptic) connection between two neurons, but our signal propagation measurements reflect contributions from all paths through the network (Fig. 3a). To compare", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 401, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "54d6d537-e71a-437e-8e38-69f1562a0a2b": {"__data__": {"id_": "54d6d537-e71a-437e-8e38-69f1562a0a2b", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.5, para 0](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "da3dd82a-e77b-4cdb-ac91-7dd4b49293f7", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.5, para 0](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "11860f90a0212434779662200fb6d0872301cc8ca3b6bf1cbe455cb0e2399ccf", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Article", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 9, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0cc3e893-28be-4262-88ef-c3683285db7c": {"__data__": {"id_": "0cc3e893-28be-4262-88ef-c3683285db7c", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.5, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "afbbc599-7fdb-4313-9df9-3414e91359db", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.5, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "22db47cd34a79b1468b745036241fc18a7b184fac8656a5c9b40413c2cb5a484", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Fig. 3 | Functional measurements differ from anatomy-based predictions.\na, Signals propagate along all paths, including indirect and recursive (coloured). Anatomical descriptions such as synapse count describe only direct paths (black). Connectome-constrained simulations are therefore used to predict signal propagation from anatomy. b, Pairs predicted from anatomy to have large downstream responses (\\Delta V > 0.1V, n = 23,454 pairs) tend to have stronger measured responses (larger \\Delta F/F\\_0) than do those predicted to have small responses (\\Delta V  0.1V, compared to functionally non-connected pairs (P < 0.0001, one-sided Kolmogorov\u2013Smirnov test). d, Agreement of measured responses to anatomy-predicted responses is shown for WT (green) and unc-31 (cyan) animals, either using weights and signs from anatomy, or when weights and signs are fitted optimally. Agreement is reported as R^2 coefficient for the line of best fit: \\Delta F/F\\_0 = m\\Delta V. Perfect agreement would be R^2 = 1.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1000, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c61bbb8f-f93c-4a8a-a4c0-c43d4a17c4f4": {"__data__": {"id_": "c61bbb8f-f93c-4a8a-a4c0-c43d4a17c4f4", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.5, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6a0fad78-2d9f-4134-abd7-41b01adedb40", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.5, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "8e30990d67c59edc9f776d9641f4ddae92ec0b748bee4515873c0a8b9d35092d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "the two, we relied on a connectome-constrained biophysical model that predicts signal propagation from anatomy, considering all paths. We activated neurons in silico and simulated the network's predicted response using synaptic weights from the connectome^1,6, polarities estimated from gene expression^37 and common assumptions about timescales and dynamics^47.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 362, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "452e980f-cd73-441c-a600-457fcad4d905": {"__data__": {"id_": "452e980f-cd73-441c-a600-457fcad4d905", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.5, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "727f142f-a1aa-4c8b-986c-38c7336c0181", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.5, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "5264de69d975b9d2619e3a5d2d8073e472b8f6f2cdfc4c3cc6e1c1293cd7182e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The anatomy-derived biophysical model made some predictions that agreed with our measurements. Neuron pairs that the model predicted to have large responses (\\Delta V > 0.1) were significantly more likely to have larger measured responses than were those predicted to have little or no response (\\Delta V  0.1) compared to pairs that our measurements deem functionally non-connected (q\\_eq < 0.05), (Fig. 3c, top).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 414, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7ed4adaf-c033-4547-a666-c79ef02ff369": {"__data__": {"id_": "7ed4adaf-c033-4547-a666-c79ef02ff369", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.5, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "796b5ee0-3b55-4b29-a2a9-7a21c258548d", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.5, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "2372a1830a19f46627a94514c229dc9caae65d2e4e4ccaff1172964a3f2ce70c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Overall, however, there was fairly poor agreement between anatomy-based model predictions and our measurements. For example, we measured large calcium responses in neuron pairs that were predicted from anatomy to have almost no response (Fig. 3c). There was also poor agreement between anatomy-based prediction and measurement when considering the response amplitudes of all neuron pairs (Fig. 3d, R^2 < 0, where an R^2 of 1 would be perfect agreement).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 453, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "801d8d54-9aa4-4f51-8522-0c8f037ef07e": {"__data__": {"id_": "801d8d54-9aa4-4f51-8522-0c8f037ef07e", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.5, para 5](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "05adfa6c-9d83-49a8-a871-6447a720efb3", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.5, para 5](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "de1dbfbf68b79c8bbf571ce85d94c86725a3559ffc70e7f1b663830e73c0e590", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Fundamental challenges in inferring the properties of neural connections from anatomy could contribute to the disagreement between anatomical-based model predictions and our measurements. It is challenging to infer the strength and sign of a neural connection from anatomy when many neurons send both excitatory and inhibitory signals to their postsynaptic partner^11,37. AFD\u2192AIY, for example, expresses machinery for inhibiting AIY through glutamate, but is excitatory owing to peptidergic signalling^48 (Extended Data Fig. 2g). We therefore wondered whether agreement between structure and function would improve if we instead fitted the strength and sign of the wired connections to our measurements. Fitting the weights and signs, given simplifying assumptions, but forbidding new connections that do not appear in the wiring diagram, improved the agreement between the anatomical prediction and the functional measurements, although overall agreement remained poor (Fig. 3d). We therefore investigated whether additional functional connections exist beyond the connectome. We measured signal propagation in unc-31-mutant animals, which are defective for extrasynaptic signalling mediated by dense-core vesicles, as explained below. Although agreement was still poor, signal propagation in these animals showed better agreement with anatomy than it did in WT animals (Fig. 3d). This prompted us to consider extrasynaptic signalling further.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1444, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "011505b5-4a94-481b-9fad-13678da5452a": {"__data__": {"id_": "011505b5-4a94-481b-9fad-13678da5452a", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.5, para 6](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6c68b545-0dac-4974-a1f4-b59921b75c0d", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.5, para 6](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "14910a89465f0b6a1cde41e42813a25a9885313eece347da63a94a5cdf5d55c3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Extrasynaptic signalling also drives neural dynamics", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 55, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4f9b5da1-273f-48e1-ba6a-7fd5c448e4a7": {"__data__": {"id_": "4f9b5da1-273f-48e1-ba6a-7fd5c448e4a7", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.5, para 7](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "313405c0-b44d-4945-9eaf-a958556fcfd2", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.5, para 7](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "296a6205ed9ae6722f1d29158a9b8aa14dc17c4410cfd1a5e3df3cb385addbb2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Neurons can communicate extrasynaptically by releasing transmitters, often via dense-core vesicles, that diffuse through the extracellular milieu to reach downstream neurons instead of directly traversing a synaptic cleft (Supplementary Information). Extrasynaptic signalling forms an additional layer of communication not visible from anatomy^49 and its molecular machinery is ubiquitous in mammals^50 and *C. elegans*^38,51,52.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 429, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3875cfc8-979e-41b6-95ba-ecebabfc5a15": {"__data__": {"id_": "3875cfc8-979e-41b6-95ba-ecebabfc5a15", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.5, para 8](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "551dc09b-175a-4254-997f-bde5869612b9", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.5, para 8](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "c35a225dda2fab2fdbc4341ce6319c3a3b606e9857812e3c17f58adfce5165a2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "To examine the role of extrasynaptic signalling, we measured the signal propagation of unc-31-mutant animals defective for dense-core-vesicle-mediated release (Extended Data Fig. 7a; 18 individuals) and compared the results with those from WT animals (browsable online at", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 271, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "914ece0b-6dd7-4b3c-a1ab-e181da8a1974": {"__data__": {"id_": "914ece0b-6dd7-4b3c-a1ab-e181da8a1974", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.5, para 9](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f5ad4033-d769-413c-acd2-6ad17037d96b", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.5, para 9](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "45e21d71b5d989b772a4f5f8900742d7140de451a471c81f8160d50132f0c805", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "). This mutation disrupts dense-core-vesicle-mediated extrasynaptic signalling of peptides and monoamines by removing UNC-31 (CAPS), a protein involved in dense-core-vesicle fusion^53.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 184, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "29773f6d-5039-4f29-9643-8255b4519dc4": {"__data__": {"id_": "29773f6d-5039-4f29-9643-8255b4519dc4", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.5, para 10](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "73469a32-50ed-470d-8cec-058a2248f1dc", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.5, para 10](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "f8338ab7b9fdfaf06edcd6a8b8a07c692173c1d39d309eab938f9ea647189e40", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We expected that most signalling in the brain visible within the time-scales of our measurements (30 s) would be mediated by chemical or electrical synapses and would therefore be unaffected by the unc-31 mutation. Consistent with this, many individual functional connections that we observed in the WT case persisted in the unc-31 mutant (Extended Data Fig. 8). But if fast dense-core-vesicle-dependent extrasynaptic signalling were present, it should be observed only in WT and not in unc-31-mutant individuals. Consistent with this, unc-31 animals had a smaller proportion of functional connections than did WT animals (Extended Data Fig. 7b).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 646, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4c68bdb2-577b-463d-aa61-47d4abe81273": {"__data__": {"id_": "4c68bdb2-577b-463d-aa61-47d4abe81273", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.5, para 11](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3025db6f-623a-46b6-bb93-3f7d7a7fbbe9", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.5, para 11](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "356106d6331e94377c241c99c5a6ad021702ae451dae8fb814fd7a82073f2b99", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We investigated the neuron RID, a cell that is thought to signal to other neurons extrasynaptically through neuropeptides, and that has", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 135, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4071b05d-c83e-4b4d-8a00-6f10f147fd89": {"__data__": {"id_": "4071b05d-c83e-4b4d-8a00-6f10f147fd89", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.5, para 12](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "690944b0-f0b7-403c-96ba-b1d75d99868c", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.5, para 12](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "16d8c824d851b12bad449a82b71aad8753ec68b61202304832cbe303f4ce759f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "```html\n\n|Agreement with anatomy (R^2)|\\Delta F/F\\_0 versus \\Delta V|\n|-|-|\n|\u20130.04|unc-31|\n|\u20130.08|WT|\n\n```", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 106, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2c9dcaf1-ae5f-4478-9998-b291dac52ec0": {"__data__": {"id_": "2c9dcaf1-ae5f-4478-9998-b291dac52ec0", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.5, para 13](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a500cff1-fe6e-43af-97da-b828ee70f5fa", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.5, para 13](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "64400448fc33e4019bcbae0dcb4b473e6e47a9f865315c0c605efc6c8d0a60d1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "```html\n\n|Functionally connected (q < 0.05)|Functionally not connected (q\\_eq < 0.05)|\n|-|-|\n|Blue|Orange|\n\n```", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 111, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a45cf30e-d376-4125-b4b8-4f82032ea765": {"__data__": {"id_": "a45cf30e-d376-4125-b4b8-4f82032ea765", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.5, para 14](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0d6f10b0-7e45-4ce7-83ab-273177f3d9e1", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.5, para 14](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "e7da7ea5da8fdf76b6e1992079793755f3f243f5279b5fa2964a2c6722910472", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "```html\n\n|Measured \\Delta F/F\\_0|Anatomy-derived response (biophysical model)|\n|-|-|\n|2|\\Delta V \\leq 0.1|\n|1|\\Delta V > 0.1|\n\n```", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 130, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0590220a-9d4f-423f-a0e7-543f1e5c45bd": {"__data__": {"id_": "0590220a-9d4f-423f-a0e7-543f1e5c45bd", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.6, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2a5d2402-939b-400b-94b5-81a4f1a22f9e", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.6, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "d21f81c4ee79e15d008974d7d0fe6de5b66b67c55662fd9fbf666f878a438bdc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Fig. 4** | Anatomy does not capture extrasynaptic signalling from the neuron RID. a, ADL, AWB and URX are predicted from anatomy to have no response to RID stimulation because there is no strong anatomical path from RID to those neurons (vertical lines at or near 0 V). Their anatomy-predicted responses are shown within the distribution of anatomy-predicted responses for all neuron pairs (blue histogram), as in Fig. 3b. b\u2013d, Activity of neurons URXL (b), ADLR (c) and AWBR (d) to RID stimulation, in WT and unc-31 mutant backgrounds. Top, mean (blue) and s.d. (shading) across trials and animals. Bottom, individual traces are sorted across trial and animal by mean response amplitude. Here, trials are shown even in cases when RID activity was not measured. Additional neurons are shown in Extended Data Fig. 7c.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 818, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "86c63998-b3c9-43f8-9302-d8aa90d87b9e": {"__data__": {"id_": "86c63998-b3c9-43f8-9302-d8aa90d87b9e", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.6, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2a54e20b-d0a9-46cf-acde-f111f9efce07", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.6, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "88b0b3b89f29838a353699e4b576ff89e7fecb0275347ea5db09ebe4cb928456", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "only few and weak outgoing wired connections^54. RID had dim tagRFP-T expression, so we adjusted our analysis protocol for only this neuron, as described in the Methods. Many neurons responded to RID activation (Extended Data Fig. 7c), including URX, ADL and AWB, three neuron subtypes that were predicted from anatomy to have no response (Fig. 4a). These three neurons showed strong responses in WT animals but their responses were reduced or absent in unc-31 mutants (Fig. 4b\u2013d), consistent with dense-core-vesicle-mediated extrasynaptic signalling. The gene expression and wiring of these neurons also suggest that peptidergic extrasynaptic signalling is producing the observed responses. All three express receptors for peptides produced by RID (NPR-4 and NPR-11 for FLP-14 and PDFR-1 for PDF-1), and no direct (monosynaptic) wiring connects RID to URX, ADL or AWB: a minimum of two hops are required from RID to URXL or AWBR, and three from RID to ADLR. These shortest paths all rely on fragile single-contact synapses that appear in only one out of the four individual connectomes^6. We conclude that RID signals to other neurons extrasynaptically, and that this is captured by signal propagation measurements but not by anatomy.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1235, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "27c02ad3-8bec-4039-a925-70de043e09e7": {"__data__": {"id_": "27c02ad3-8bec-4039-a925-70de043e09e7", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.6, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "473b140d-c29b-4ab1-9079-c40536e05955", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.6, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "6991de3bfbd90a2bb99df7823df69f2d5493d712dd25d417d20a9e9a5d130ac8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Extrasynaptic-dependent signal propagation screen", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 53, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "96201b91-132c-490e-b4f5-047649548606": {"__data__": {"id_": "96201b91-132c-490e-b4f5-047649548606", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.6, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6cb508e6-027f-4119-a37d-23c542a2c754", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.6, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "458e550fddd704dc3e6acc70078b34b5946eb8d4ea1b54ab0575048ff20619d8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "To identify new pairs of neurons that communicate purely extrasynaptically, we performed an unbiased screen and selected for neuron pairs that had functional connections in WT animals (q < 0.05) but were functionally non-connected in unc-31 mutants (q\\_eq < 0.05). Fifty-three pairs of neurons met our criteria (Extended Data Fig. 9), and were therefore putative candidates for purely extrasynaptic signalling. This is likely to be a lower bound because many more pairs could communicate extrasynaptically but might not appear in our screen, either because they don\u2019t meet our statistical threshold or because they communicate through parallel paths, of which only some are extrasynaptic. Other scenarios not captured by the screen, and additional caveats, are discussed in the Supplementary Information. The timescales of", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 822, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "88ded2e9-9d53-4b54-93ce-55a7c3f664c3": {"__data__": {"id_": "88ded2e9-9d53-4b54-93ce-55a7c3f664c3", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.6, para 5](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cdd72563-8420-44a7-b13c-591287ea9c6e", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.6, para 5](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "9d12ee3bed0a0d3c39de224500d2d9fce6bd8f1b2af712ffadb975dcb4783e90", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "signal propagation for those neuron pairs that passed our screen were similar to that of all functional connections (Fig. 5a), suggesting that in the worm, unc-31-dependent extrasynaptic signalling can also propagate quickly.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 225, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ee2ebf2d-63cc-4df2-8a6b-3701e9179cd6": {"__data__": {"id_": "ee2ebf2d-63cc-4df2-8a6b-3701e9179cd6", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.6, para 6](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7a504c07-e53d-4b01-9aca-9b96e61989fa", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.6, para 6](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "dce3975a65701df0c9745827d16865a93d0cec314810350dd6d20082ce739ee0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Neuron pair M3L\u2192URYVL is a representative example of a purely extrasynaptic-dependent connection found from our screen. There are no direct chemical or electrical synapses between M3L and URYVL, but stimulation of M3L evokes unc-31-dependent calcium activity in URYVL (Fig. 5b). The majority of neuron pairs identified in our screen express peptide and receptor combinations consistent with extrasynaptic signalling^38,52 (Supplementary Table 1). For example, M3L expresses FLP-4, which binds to the receptor NPR-4, expressed by URVYL; and FLP-5, which binds to the receptor NPR-11, also expressed by URYVL.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 607, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "90a77188-bca9-4443-8d43-f88f71e53c08": {"__data__": {"id_": "90a77188-bca9-4443-8d43-f88f71e53c08", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.6, para 7](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4e4813c8-9458-46b9-8518-a911d481ee2d", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.6, para 7](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "88920371b866dcc0611f9910b3758a1f39a7c2fefe23cb5f495be55c36247120", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The bilateral neuron pair AVDR and AVDL was also identified in our screen for having purely extrasynaptic-dependent connections. AVDR and AVDL have no or only weak wired connections between them (three of four connectomes show no wired connections, and the fourth finds only a very weak gap junction), but stimulation of AVDR evoked robust unc-31-dependent responses in AVDL. Notably, the AVD cell type was recently predicted to have a peptidergic autocrine loop^51 mediated by the neuropeptide\u2013GPCR combinations NLP-10\u2192NPR-35 and FLP-6\u2192FRPR-8 (refs. 38,52) (Fig. 5c). The bilateral extrasynaptic signalling that we observe is consistent with this prediction because two neurons that express the same autocrine signalling machinery can necessarily signal to one another. AVD was also predicted to be among the top 25 highest-degree \u2018hub\u2019 nodes in a peptidergic network based on gene expression^51, and, in agreement, AVD is highly represented among hits in our screen (Extended Data Fig. 9b).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 992, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "104274fb-0cd2-4af8-a491-2111ad3fbb44": {"__data__": {"id_": "104274fb-0cd2-4af8-a491-2111ad3fbb44", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.6, para 8](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f69f58e8-2a85-4ca2-a5f5-930a054e4a15", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.6, para 8](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "224db351070cfa55abd2ecbd08bb57a839038b498bd51d19ad90ac098bb055a4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Signal propagation predicts spontaneous activity", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 52, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "43f64bad-5ea4-4991-876b-58ce7b43e58d": {"__data__": {"id_": "43f64bad-5ea4-4991-876b-58ce7b43e58d", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.6, para 9](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cc25d3a9-6c33-4b8a-8e8a-9ab9f919889d", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.6, para 9](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "fb4a4c40b3449a972405ab9f3ab7536d40a194a5e49c97bf581055d44e0a172d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "A key motivation for mapping neural connections is to understand how they give rise to collective neural dynamics. We tested the ability", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 136, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "49fc0213-3c21-495d-9b20-52bfe8fe39b5": {"__data__": {"id_": "49fc0213-3c21-495d-9b20-52bfe8fe39b5", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.7, para 0](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7431831d-146f-411a-b7f8-220365512205", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.7, para 0](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "8ff0bf0be6e82aa02395918ba0aa31b719669ad74f35786512837749a6cb9380", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Article", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 9, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0198f46d-c171-43fe-a9f6-ae045d420ec1": {"__data__": {"id_": "0198f46d-c171-43fe-a9f6-ae045d420ec1", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.7, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5d2c913a-de02-4363-b27e-c0c4903e8464", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.7, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "8cc2ded693c8b0544ccbfbad2ae381b1614feecbf55cdbdcf9980109f55b9994", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Fig. 5 | Candidate purely extrasynaptic-dependent functional connections.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 76, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c14fda29-41da-4be3-9e21-d29a12fef45c": {"__data__": {"id_": "c14fda29-41da-4be3-9e21-d29a12fef45c", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.7, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "672aa420-74e1-43d3-91ec-96e4ef24d00d", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.7, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "33d4bd098caa254b089b42459f36df7f8f2ff1e9e188d3dd40e2864a82c61acc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "a, Distribution of signal propagation timescales. b, c, Paired responses for M3L\u2192URYVL (b) and AVDR\u2192AVDL (c), for WT and unc-31 animals. unc-31 animals do not show downstream responses to stimulation. AVDR\u2192AVDL extrasynaptic communication is putatively mediated in autocrine loops through NLP-10\u2192NPR-35 and FLP-6\u2192FRPR-8 signalling. Top, average (blue) and s.d. (shading) across trials and animals.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 397, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "94062043-fa0f-4a43-ae1f-cd1e3d301281": {"__data__": {"id_": "94062043-fa0f-4a43-ae1f-cd1e3d301281", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.7, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "05d7d2e0-b8d6-4dba-a8a2-5a9fda3db347", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.7, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "909d1533d8b50c11ec430b0dc51f6e42fcf7cca4807f6c8582597f5e54de0ce4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "of our signal propagation map to predict worms' spontaneous activity, and compared this to predictions from anatomy (Fig. 6). Spontaneous activity was measured in immobilized worms lacking optogenetic actuators under bright imaging conditions. A matrix of bare anatomical weights (synapse counts) was a poor predictor of the correlations of spontaneous activity (left bar, Fig. 6), consistent with previous reports^27,41. The connectome-constrained biophysical model from Fig. 3 better predicted spontaneous activity correlations (middle bars, Fig. 6; described in the Methods)\u2014as we would expect because it considers all anatomical paths through the network\u2014but it still performed fairly poorly. Predictions based on our functional measurements of signal propagation kernels (right bars, Fig. 6) performed best of all at predicting spontaneous activity correlations. To generate predictions of correlations either from the biophysical model or from our functional kernel measurements required the activity of a set of neurons to be driven in silico. For the biophysical model, driving all neurons was optimal, but for the kernel-based predictions, driving a specific set of six neurons ('top-n') markedly improved performance. We conclude that functionally derived predictions based on our measured signal propagation kernels better agree with spontaneous activity than do either a bare description of anatomical weights or an established model constrained by the connectome, and that some subsets of neurons make outsized contributions to driving spontaneous dynamics. The kernel-based simulation (interactive version at", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1622, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "93052589-29e0-40ab-b010-136e75668050": {"__data__": {"id_": "93052589-29e0-40ab-b010-136e75668050", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.7, para 5](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e89050a8-451d-4ae7-beeb-0a162280516f", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.7, para 5](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "55db0dcd45e2e9d5980b87f3c24b667192a0da98e3b207c1c13ff82f437a471e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ") outperforms other models of neural dynamics presumably for two reasons: first, it extracts all relevant parameters directly from", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 130, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7617d075-ebc1-4c07-8a8f-8ae1a6e2e2ad": {"__data__": {"id_": "7617d075-ebc1-4c07-8a8f-8ae1a6e2e2ad", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.8, para 0](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "83afd0de-252e-40d1-819c-7fd2af4bf33f", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.8, para 0](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "6bf0b72a53aba969e96e11ecf4fa86da74558589aee3db66ed4e3c00b4932894", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Fig. 6 | Measured signal propagation better predicts spontaneous activity than anatomy does.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 92, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "eb817032-8953-4e89-8f3c-99120e96603e": {"__data__": {"id_": "eb817032-8953-4e89-8f3c-99120e96603e", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.8, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "eef3d3eb-43b3-41e7-b86e-6fc869b21266", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.8, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "b3fcf64f0a18a6f507a04d4ccc219b23f1d1b2a9f55ade259451f4230f31fa33", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Agreement with spontaneous activity correlations (Pearson\u2019s corr. coeff.)|0.7All driven|0.7Top-n driven|0.7N/A||\n|-|-|-|-|-|\n|Anatomical weights|0.0|0.0|0.0||\n|Anatomy-derived correlations (biophysical model)|0.1|0.1|0.0||\n|Functionally derived correlations|0.2|0.6|0.6||", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 272, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e3503a24-4e6e-4d96-8797-b4183900ef9d": {"__data__": {"id_": "e3503a24-4e6e-4d96-8797-b4183900ef9d", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.8, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9196cf04-84d6-4361-845d-d4de3b15b93c", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.8, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "958470002ce163024a2a37ae69c581e2b1999429bdf2451bbd031b220d1efd78", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Agreement (as Pearson\u2019s correlation (corr.) coefficient (coeff.)) between the correlation matrix of spontaneous activity recorded from an immobilized animal and various predictions of those correlations, including: the bare anatomical weight matrix (synapse counts) (left); correlations predicted by the anatomy-derived biophysical model (middle); and correlations functionally derived from the measured signal propagation kernels (right). Anatomy-derived and functionally derived correlations are calculated by driving activity in silico in all neurons (dark blue) or only an optimal subset of top-n neurons (light blue). NA, not applicable.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 642, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9d6491a9-0981-469c-a941-a0e39a8b109d": {"__data__": {"id_": "9d6491a9-0981-469c-a941-a0e39a8b109d", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.8, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0fa8c61d-3588-40b0-8526-e298e6595e3b", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.8, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "cf98b2cdddb602d0743e2c02d577315a3d55d3fcf6df5081381f3f69d462da83", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "questions that motivate our work, such as how a stimulus in one part of the network drives activity in another. Direct connections are suited for questions of gene expression, development and anatomy, but less so for network function. For example, a direct connection between two neurons could be slow or weak, but might overlook a fast and strong effective connection via other paths through the network.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 405, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "adad9bca-aaf4-4dfa-af15-0c8b31b0d054": {"__data__": {"id_": "adad9bca-aaf4-4dfa-af15-0c8b31b0d054", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.8, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d0fc7338-e6b7-4f1c-91b5-f28763da1026", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.8, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "aebce563eb0003fb450254783f173026f16ab81f11302f1d57028bc208507154", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We used a connectome-constrained biophysical model to provide additional evidence to support our claim that measured signal propagation differs from expectations based on anatomy. The model relies on assumptions of timescales, nonlinearities and other parameters that, if incorrect, would contribute to the observed disagreement between anatomy and function. But even without any biophysical model, discrepancies between anatomy and function are apparent; for example, in pairs of neurons with synaptic connections that are functionally non-connected (Fig. 2g), and in strong functional connections between RID and other neurons that have only weak, variable and indirect synaptic connections (Fig. 4). The challenge of confidently constraining model parameters from anatomy highlights the need for functional measurements, like the ones performed here. These functional measurements fill in fundamental gaps in the translation from anatomical connectome to neural activity. An alternative approach for comparing structure and function would be to infer properties of direct connections from the measured effective connections^55, but this might require a higher signal-to-noise ratio than our current measurements.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1215, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ca9e7b36-cbe1-408c-b76f-403438a14152": {"__data__": {"id_": "ca9e7b36-cbe1-408c-b76f-403438a14152", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.8, para 5](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ab623138-6500-4948-838c-5804bed90cbb", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.8, para 5](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "6f6f6a41324837c27b815f871b7c61bf4d809b446d7140be7f897b5b6d33dd41", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The signal propagation atlas presented here informs structure\u2013function investigations at both the circuit and the network level, and enables more accurate brain-wide simulations of neural dynamics. The finding that extrasynaptic peptidergic signalling, which is invisible to anatomy, evokes neural dynamics in *C. elegans* will inform ongoing discussions about how to characterize other brains in more detail and on a larger scale.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 431, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f35065ad-5df2-4096-bdec-cc383193786c": {"__data__": {"id_": "f35065ad-5df2-4096-bdec-cc383193786c", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.8, para 6](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b763ca6c-2ee1-4276-bcfb-bc6d472f17c2", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.8, para 6](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "053181d7d6528c0fd7f385a1f8afcd443c9ed2c645018e9d013f8ca99b2d791b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "the measured kernels, thereby avoiding the need for many assumptions; and second, it captures extrasynaptic signalling not visible from anatomy.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 144, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b299b712-1ebf-4f43-917d-b94256c0703c": {"__data__": {"id_": "b299b712-1ebf-4f43-917d-b94256c0703c", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.8, para 7](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "45fa3f51-e7ac-4bee-9260-4056e674f990", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.8, para 7](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "2a980bcd5bb399047cd55696b91547d1511b9fbd894d103b38ca04e563431976", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Discussion", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 13, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "28407e59-c3bf-4204-a829-0922f47756b0": {"__data__": {"id_": "28407e59-c3bf-4204-a829-0922f47756b0", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.8, para 8](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "19f86b1f-4de6-4d7e-a3c6-62c965615e73", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.8, para 8](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "75d388f021f2cc0eccedc455ae425be2a763a938a3fb7eb867cd895f0428fd54", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Signal propagation in *C. elegans* measured by neural activation differs from model predictions based on anatomy, in part because anatomy does not account for wireless connections such as the extrasynaptic release of neuropeptides^49.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 234, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "452ae98e-4b25-41a0-b948-8cda515144ad": {"__data__": {"id_": "452ae98e-4b25-41a0-b948-8cda515144ad", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.8, para 9](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "59971d0b-54ed-47f2-a584-732dc44dac3f", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.8, para 9](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "c1f8e9d8a1f61f9d648e244e729ac5113968eab9fd5479a8458ac2406acd36ab", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "By directly evoking calcium activity on a timescale of seconds, extrasynaptic signalling serves a functional role similar to that of classical neurotransmitters and contributes to neural dynamics. This role is in addition to its better-characterized role in modulating neural excitability over longer timescales.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 312, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ee5758cf-af38-40af-8b92-fb1ec2ded8bd": {"__data__": {"id_": "ee5758cf-af38-40af-8b92-fb1ec2ded8bd", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.8, para 10](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "579f11de-4d59-42d5-bcb1-1c2cbee9216d", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.8, para 10](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "fcf80212e8decae5534f51571a6c1f6779f4f5e0315f51ea18b8c9db6df5c16b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Peptidergic extrasynaptic signalling relies on diffusion and therefore may be uniquely well suited to *C. elegans*' small size. Mammals also express neuropeptides and receptors, including in the cortex^50, but their larger brains might limit the speed, strength or spatial extent of peptidergic extrasynaptic signalling.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 320, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0cc1761a-7c7d-4ce8-8660-8d3fd2cbcd4d": {"__data__": {"id_": "0cc1761a-7c7d-4ce8-8660-8d3fd2cbcd4d", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.8, para 11](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "213ee305-bde0-499e-aba3-ca66d0e7b76b", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.8, para 11](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "a758fecff38875d988cadc3181ff46a33b3b448c0e47ec6ae370b62563280fd4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Plasticity, neuromodulation, neural-network state, experience dependence and other longer-timescale effects might contribute to variability in our measured responses or to discrepancies between anatomical and functional descriptions of the *C. elegans* network. A future direction will be to search for latent connections that might become functional only during certain internal states.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 387, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cfa3d27a-8121-4aa6-aee2-2e0d568a4c89": {"__data__": {"id_": "cfa3d27a-8121-4aa6-aee2-2e0d568a4c89", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.8, para 12](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "529dff07-87d3-497c-97ad-f29bd8de0fc4", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.8, para 12](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "33d33701dba6a5df4bc72593cd8f489e33d4725f84dfd70dc51f7b56940c28e4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Our signal propagation map provides a lower bound on the number of functional connections (Supplementary Information). Our measurements required a trade-off between the animal\u2019s health and its transgenic load. To express the necessary transgenes, we generated a strain that is not behaviourally wild type; its signal propagation might therefore also differ from the wild type. To probe nonlinearities and multi-neuron interactions in the network, future measurements are needed of the network\u2019s response to simultaneous stimulation of multiple neurons.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 552, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "dd8b6469-b0b6-4e65-b7af-475b9f6580a1": {"__data__": {"id_": "dd8b6469-b0b6-4e65-b7af-475b9f6580a1", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.8, para 13](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7a54481d-c79a-4b43-a417-0179ccf87459", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.8, para 13](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "aea0f1915fc49ae735bc80518a8036bc125646766fb127142411b16c7acf2f0f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Our signal propagation map reports effective connections, not direct connections. Effective connections are useful for the circuit-level", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 136, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e40f67fe-3db6-4c8d-a872-b31650812f76": {"__data__": {"id_": "e40f67fe-3db6-4c8d-a872-b31650812f76", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.8, para 14](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0f7fdb94-7b7a-45e2-92e4-450c76e10568", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.8, para 14](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "a4b7a18c325a0d1b30ee542a1b78389768885173e6e18a0eed142b317bfff827", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Online content", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 17, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2aa8a845-ff64-4152-b7ce-a502ab4d1d8f": {"__data__": {"id_": "2aa8a845-ff64-4152-b7ce-a502ab4d1d8f", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.8, para 15](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "276faf64-e278-4c2a-a981-044329d412b6", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.8, para 15](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "5f107a9965c0407cf6a702e3a5ab6a67adb309a74099028243afc41d06641cce", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Any methods, additional references, Nature Portfolio reporting summaries, source data, extended data, supplementary information, acknowledgements, peer review information; details of author contributions and competing interests; and statements of data and code availability are available at", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 290, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b1bf07ef-79ed-4cca-b285-4a1d76f28de1": {"__data__": {"id_": "b1bf07ef-79ed-4cca-b285-4a1d76f28de1", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.8, para 16](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c8daac09-6c91-46d3-9194-9474b210a6cb", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.8, para 16](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "0a81b5e781e16f76c591b0541669de43beb86642944159a339300c13c554802f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ".", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8d6c6af6-a897-418c-9c55-81794badad38": {"__data__": {"id_": "8d6c6af6-a897-418c-9c55-81794badad38", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.8, para 17](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9622473e-6291-4c19-8748-9e94fffe52e0", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.8, para 17](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "9b1655d57fa9cba47e1283530b0b3858b6ced7f51c41d020b103d8c357caf47c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "1. 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Lett.* **126**, 118102 (2021).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 6449, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0683354d-ea5d-4748-8a37-f155235a5c85": {"__data__": {"id_": "0683354d-ea5d-4748-8a37-f155235a5c85", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.9, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3e523791-799b-43cf-8d26-63fbb4d1fa69", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.9, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "3050cec6e0d6f63a6eb0dccd86891b7d33f50709bca02d56050d6f92b73d1363", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 135, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c224fd64-3214-4f94-b34a-6002f15d8e76": {"__data__": {"id_": "c224fd64-3214-4f94-b34a-6002f15d8e76", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.9, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c4bd5175-96f0-4bc9-b510-238fdbf74141", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.9, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "35e9f776cc1b2790f7996f05fba90f5b6073f3beebda702adf36143e40f2daec", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article\u2019s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article\u2019s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 805, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "109c2dba-b9db-4c24-902e-f7e5433d27a4": {"__data__": {"id_": "109c2dba-b9db-4c24-902e-f7e5433d27a4", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.9, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "29e8b12a-9710-408f-bce9-bfb4e166a837", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.9, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "962fefc37c8e4528821f5e79b6175069cedddebbededa25f31dce465db280e41", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ".", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "45847640-4f0c-4824-83a3-e78d04892e8d": {"__data__": {"id_": "45847640-4f0c-4824-83a3-e78d04892e8d", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.10, para 0](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8af7f095-6549-4d69-8363-d4e6179a7250", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.10, para 0](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "a60129cb7ac24ad410c6559b982fdaece7be0d9ea32b316cd777642fb35710a8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Methods", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 9, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c9076549-a804-49f0-a33f-361e1d6826f7": {"__data__": {"id_": "c9076549-a804-49f0-a33f-361e1d6826f7", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.10, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "35ca8575-1fad-4f01-864f-4d8b551ac1e3", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.10, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "ea94580c7a032e06915247928225a68662ac5ab10eaa3be026a211dcd54567cc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Worm maintenance", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 19, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0aad3b47-166b-4c51-a0ed-fb319611fe29": {"__data__": {"id_": "0aad3b47-166b-4c51-a0ed-fb319611fe29", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.10, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5d8be597-a0a0-422a-9e62-da96eda6f8d6", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.10, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "3006767fb893f556a9d2169da87bdb38a8c95e712d0e532d28d958244a04c9e9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "C. elegans were stored in the dark, and only minimal light was used when transferring worms or mounting worms for experiments. Strains generated in this study (Extended Data Fig. 1a) have been deposited in the Caenorhabditis Genetics Center (CGC), University of Minnesota, for public distribution. Hermaphrodites were used in this study.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 337, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "126359cd-d4f0-4945-8a81-03c97339ca56": {"__data__": {"id_": "126359cd-d4f0-4945-8a81-03c97339ca56", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.10, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "96b0a636-ec52-464a-84a2-8da367a018a1", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.10, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "ab869fae07aba6a49f0ed617c2254fc38375e520cfc257494ccecdde15a50237", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Transgenics", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 14, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "943d31ce-b314-4e3d-98c3-51122d722acc": {"__data__": {"id_": "943d31ce-b314-4e3d-98c3-51122d722acc", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.10, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e33dfb32-fc0d-4c00-8558-216f62e0c2df", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.10, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "eea8b8b129e9d9d36391903e07b8fc9d235c89fe85852693a5d38fb3fd0fd93e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We generated a transgenic worm for interrogating signal propagation, TWISP (AML462), which has been described in more detail previously^23. This strain expresses the calcium indicator GCaMP6s in the nucleus of each neuron; a purple-light-sensitive optogenetic protein system (GUR-3 and PRDX-2) in each neuron; and multiple fluorophores of various colours from the NeuroPAL^27 system, also in the nucleus of neurons. We also used a QF-hGR drug-inducible gene-expression strategy to turn on the gene expression of optogenetic actuators only later in development. To create this strain, we first generated an intermediate strain, AML456, by injecting a plasmid mix (75 ng \u03bcl^\u22121 pAS3-5xQUAS::\u0394 pes-10P::AI::gur-3G::unc-54 + 75 ng \u03bcl^\u22121 pAS3-5xQUAS::\u0394 pes-10P::AI::prdx-2G::unc-54 + 35 ng \u03bcl^\u22121 pAS-3-rab-3P::AI::QF+GR::unc-54 + 100 ng \u03bcl^\u22121 unc-122::GFP) into CZ20310 worms, followed by UV integration and six outcrosses^56,57. The intermediate strain, AML456, was then crossed into the pan-neuronal GCaMP6s calcium-imaging strain, with NeuroPAL, AML320 (refs. 23,27,58).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1067, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8da3ae6d-600e-4a61-baf4-c4bff7558238": {"__data__": {"id_": "8da3ae6d-600e-4a61-baf4-c4bff7558238", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.10, para 5](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8f46cccc-f41f-4bb7-88d4-9f274b1ae8b8", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.10, para 5](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "64036ca5abe6c8d716998a98666e371df6f602f182a3d4b260df9206472c7e08", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Animals exhibited decreased average locomotion compared to the WT (mean speeds of 0.03 mm s^\u22121 off drug and 0.02 mm s^\u22121 on drug compared to the mean of 0.15 mm s^\u22121 in WT animals^23), as expected for NeuroPAL GCaMP6s strains, which are also reported to be overall less active (around 0.09 mm s^\u22121 during only forward locomotion)^27.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 333, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4a24f758-4ffc-4216-9cb5-0b7a82faddc6": {"__data__": {"id_": "4a24f758-4ffc-4216-9cb5-0b7a82faddc6", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.10, para 6](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fff271f3-24e4-4c1a-b690-7090f0d2b095", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.10, para 6](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "e909ed0f75c102d7dfe2bc5c52ad3029f431a7fd08b56ca8bf7d4d464d5c152c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "An unc-31-mutant background with defects in the dense-core-vesicle-release pathway was used to diminish wireless signalling^53. We created an unc-31-knockout version of our functional connectivity strain by performing CRISPR\u2013Cas9-mediated genome editing on AML462 using a single-strand oligodeoxynucleotide (ssODN)-based homology-dependent repair strategy^59. This approach resulted in strain AML508 (unc-31 (wtf502) IV; otIs669 (NeuroPAL) V 14x; wtfIs145 (30 ng \u03bcl^\u22121 pBX + 30 ng \u03bcl^\u22121 rab-3::his-24::GCaMP6s::unc-54); wtfIs348 (75 ng \u03bcl^\u22121 pAS3-5xQUAS::\u0394 pes-10P::AI::gur-3G::unc-54 + 75 ng \u03bcl^\u22121 pAS3-5xQUAS::\u0394 pes-10P::AI::prdx-2G::unc-54 + 35 ng \u03bcl^\u22121 pAS-3-rab-3P::QF+GR::unc-54 + 100 ng \u03bcl^\u22121 unc-122::GFP)).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 715, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0af66ca4-0522-4c6f-b1bd-d52faf89b99f": {"__data__": {"id_": "0af66ca4-0522-4c6f-b1bd-d52faf89b99f", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.10, para 7](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a9b50938-8b56-42f5-b5f3-3ca93c8a960f", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.10, para 7](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "0754e64f383742c32b34b0d2ba73d919b522ad9dbd8cf848856177891ebaf342", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "CRISPR\u2013Cas-9 editing was carried out as follows. Protospacer adjacent motif (PAM) sites (denoted in upper case) were selected in the first intron (gagcuucgcaauguugacucCGG) and the last intron (augguacauuggguccguggCGG) of the unc-31 gene (ZK897.1a.1) to delete 12,476 out of 13,169 bp (including the 5\u2032 and 3\u2032 untranslated regions) and 18 out of 20 exons from the genomic locus, while adding 6 bp (GGTACC) for the Kpn-I restriction site (Extended Data Fig. 1b). Alt-R S.p. Cas9 Nuclease V3, Alt-R-single guide RNA (sgRNA) and Alt-R homology-directed repair (HDR)-ODN were used (IDT). We introduced the Kpn-I restriction site, denoted in upper case (gacccagcgaagcaaggatattgaaaacataagtacccttgttgttgtgtGGTACCccacggacccaatgtaccatattttacgagaaatttataatgttcagg) into our repair oligonucleotide to screen and confirm the deletion by PCR followed by restriction digestion. sgRNA and HDR ssODNs were also synthesized for the dpy-10 gene as a reporter, as described previously^59. An injection mix was prepared by sequentially adding Alt-R S.p. Cas9 Nuclease V3 (1 \u03bcl of 10 \u03bcg \u03bcl^\u22121), 0.25 \u03bcl of 1 M KCL, 0.375 \u03bcl of 200 mM HEPES (pH 7.4), sgRNAs for unc-31 (1 \u03bcl each for both sites) and 0.75 \u03bcl for dpy-10 from a stock of 100 \u03bcM, ssODNs (1 \u03bcl for unc-31 and 0.5 \u03bcl for dpy-10 from a stock of 25 \u03bcM) and nuclease-free water to a final volume of 10 \u03bcl in a PCR tube, kept on ice. The injection mix was then incubated at 37 \u00b0C for 15 min before it was injected into the germline of AML462 worms. Progenies from plates showing roller or dumpy phenotypes in the F1 generation after injection were individually propagated and screened by PCR and Kpn-I digestion to confirm deletion. Single-worm PCR was carried out using GXL-PRIME STAR taq-Polymerase (Takara Bio) and the Kpn-1-HF restriction enzyme (NEB). Worms without a roller or dumpy phenotype and homozygous for deletion were confirmed by Sanger sequencing fragment analysis.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1915, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f515f9c6-b954-4782-a2bc-4d3ad197b3e0": {"__data__": {"id_": "f515f9c6-b954-4782-a2bc-4d3ad197b3e0", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.10, para 8](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cc60b3ab-09f8-4892-ab9e-05d41201b554", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.10, para 8](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "a59208313bb96e9772e9c1d8d5fefc349a2bf71af89acf66e5c872738bc0cae1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "To cross-validate GUR-3/PRDX-2-evoked behaviour responses, we generated the transgenic strain AML546 by injecting a plasmid mix (40 ng \u03bcl^\u22121 pAS3-rig-3P::AI::gur-3G::SL2::tagRFP::unc-54 + 40 ng \u03bcl^\u22121 pAS3-rig-3P::AI::prdx-2G::SL2::tagBFP::unc-54) into N2 worms to generate a transient transgenic line expressing GUR-3/PRDX-2 in AVA neurons.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 340, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4e1c679d-725b-442a-9767-c212b8c715a1": {"__data__": {"id_": "4e1c679d-725b-442a-9767-c212b8c715a1", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.10, para 9](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "11d2148c-0558-4d13-bceb-893d0415146e", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.10, para 9](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "77ea54c03cf01501dd34a11dfcc0c46b016de2e5a790579c807dc9f5f14beb08", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Cross-validation of GUR-3/PRDX-2-evoked behaviour", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 52, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a246c449-613c-4128-a25b-1a82555c991e": {"__data__": {"id_": "a246c449-613c-4128-a25b-1a82555c991e", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.10, para 10](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ab09699d-36bd-4f08-a753-6e0faa56cceb", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.10, para 10](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "a61ad19fd665b1bcd4aafcf5bc49b99923bf6d194b87682137858e5e51412f6c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Optogenetic activation of AVA neurons using traditional channelrhodopsins (for example, Chrimson) leads to reversals^45,60. We used worms expressing GUR-3/PRDX-2 in AVA neurons (AML564) to show that GUR-3/PRDX-2 elicits a similar behavioural response. We illuminated freely moving worms with blue light from an LED (peaked at 480 nm, 2.3 mW mm^\u22122) for 45 s. We compared the number of onsets of reversals in that period of time with a control in which only dim white light was present, as well as with the results of the same assay performed on N2 worms. Animals with GUR-3/PRDX-2 in AVA (n = 11 animals) exhibited more blue-light-evoked reversals per minute than did WT animals (n = 8 animals) (Extended Data Fig. 2h).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 718, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8a732839-abdd-4e72-a010-8229b823c142": {"__data__": {"id_": "8a732839-abdd-4e72-a010-8229b823c142", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.10, para 11](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "da15e696-8025-438c-b42c-01697aff4161", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.10, para 11](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "959d605814ae5579e0212ece206872a5103d342d055ba246ae216a1865cea73f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Dexamethasone treatment", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 26, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d3523e92-a424-412c-97c8-d85a53ef1a31": {"__data__": {"id_": "d3523e92-a424-412c-97c8-d85a53ef1a31", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.10, para 12](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4064fdb3-c414-4bca-af0d-e55feb325241", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.10, para 12](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "1a2b1dcac721bba96de2c7ba47d5344a78c5103808fb49b429e928ad37e3863e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "To increase the expression of optogenetic proteins while avoiding arrested development, longer generation time and lethality, a drug-inducible gene-expression strategy was used. Dexamethasone (dex) activates QF-hGR to temporally control the expression of downstream targets^61, in this case the optogenetic proteins in the functional connectivity imaging strains AML462 and AML508. Dex-NGM plates were prepared by adding 200 \u03bcM of dex in dimethyl sulfoxide (DMSO) just before pouring the plate. For dex treatment, L2/L3 worms were transferred to overnight-seeded dex-NGM plates and further grown until worms were ready for imaging. More details of the dex treatment are provided below.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 685, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9b8763c8-ddc9-4e84-9fd7-6a30e4332326": {"__data__": {"id_": "9b8763c8-ddc9-4e84-9fd7-6a30e4332326", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.10, para 13](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d5c56a28-841a-4ed3-b94e-a3f4f1b297a2", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.10, para 13](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "0c38e09e67417cd711bf0fc433bafb4998ce945198d9b4c191ee000b0cf17b1b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We prepared stock solution of 100 mM dex by dissolving 1 g dexamethasone (D1756, Sigma-Aldrich) in 25.5 ml DMSO (D8418, Sigma-Aldrich). Stocks were then filter-sterilized, aliquoted, wrapped in foil to prevent light and stored at \u221280 \u00b0C until needed. The 200-\u03bcM dex-NGM plates were made by adding 2 ml of 100 mM dex stock in 1 l NGM-agar medium, while stirring, 5 min before pouring the plate. Dex plates were stored at 4 \u00b0C for up to a month until needed.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 456, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "134e3335-168b-43f3-aaff-d5b174939530": {"__data__": {"id_": "134e3335-168b-43f3-aaff-d5b174939530", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.10, para 14](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "69c69929-fab2-4116-b6e6-4fe3102b648f", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.10, para 14](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "69ccb1dbb799d5ab0ad58337c042c52288f78937a8aad5079ffe1ad9e72cd461", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Preparation of worms for imaging", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 35, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4f783d36-b9ad-4567-9a2a-7091d7ab7333": {"__data__": {"id_": "4f783d36-b9ad-4567-9a2a-7091d7ab7333", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.10, para 15](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "78126860-36f8-431b-a573-bc38c6b0a052", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.10, para 15](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "eed58c786854fc3dc002c68756db0cead327fa114e1b1450c68164e38ea08bab", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Worms were individually mounted on 10% agarose pads prepared with M9 buffer and immobilized using 2 \u03bcl of 100-nm polystyrene beads solution and 2 \u03bcl of levamisole (500 \u03bcM stock). This concentration of levamisole, after dilution in the polystyrene bead solution and the agarose pad water, largely immobilized the worm while still allowing it to slightly move, especially before placing the coverslip. Pharyngeal pumping was observed during imaging.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 447, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e70807a5-d10f-466e-b7e7-f6ce9a04a84a": {"__data__": {"id_": "e70807a5-d10f-466e-b7e7-f6ce9a04a84a", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.10, para 16](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "054c945e-6790-4a41-9c35-193c3fd6c135", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.10, para 16](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "a54b05778c3eb6b0393524c4d108605db7d22f15681d5f2958897178f84ef29d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Overview of the imaging strategy", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 35, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "689aebaa-d081-4323-8e78-6d742dfb3875": {"__data__": {"id_": "689aebaa-d081-4323-8e78-6d742dfb3875", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.10, para 17](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "be9902d8-c839-4b30-b354-a9bd49365bf9", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.10, para 17](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "4fcd6e3e1954dacad926d76ab2c16d02fdec70b916d778fb170700d1daa791ff", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We combined whole-brain calcium imaging through spinning disk single-photon confocal microscopy^62,63 with two-photon^64 targeted optogenetic stimulation^65, each with their own remote focusing system, to measure and manipulate neural activity in an immobilized animal (Fig. 1a). We performed calcium imaging, with excitation light at a wavelength and intensity that does not elicit photoactivation of GUR-3/PRDX-2 (ref. 66) (Extended Data Fig. 2b). We also used genetically encoded fluorophores from NeuroPAL expressed in each neuron^27 to identify neurons consistently across animals (Fig. 1c).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 596, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4f090a7c-0a02-4b38-b187-73cec69f2122": {"__data__": {"id_": "4f090a7c-0a02-4b38-b187-73cec69f2122", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.11, para 0](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7320fd42-3731-40e5-83e9-d29d10232098", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.11, para 0](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "9cab83c7176f254e102950025fea098af2c8701ecc86fab1244abc6817caa723", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Article", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 9, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ad1fe408-4253-420f-a9bc-e7f1e03baf5b": {"__data__": {"id_": "ad1fe408-4253-420f-a9bc-e7f1e03baf5b", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.11, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c29b904a-5075-41ac-bbc1-deb8109e2c94", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.11, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "1d5d77ad27d755365d2ffff5f236a44aad2e29c86590781b294cfbdceee415e7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Multi-channel imaging and neural identification", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 50, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f657a0d7-8061-46a6-ae91-f159f108f6f4": {"__data__": {"id_": "f657a0d7-8061-46a6-ae91-f159f108f6f4", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.11, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2a11ef67-3b8d-492e-8da7-1201c3297433", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.11, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "b879590b6dfda7d4e2483b03b609c0caa55de24e1b2ae962ecd8b88f91c52553", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Volumetric, multi-channel imaging was performed to capture images of the following fluorophores in the NeuroPAL transgene: mtagBFP2, CyOFP1.5, tagRFP-T and mNeptune2.5 (ref. 27). Light downstream of the same spinning disk unit used for calcium imaging travelled on an alternative light path through channel-specific filters mounted on a mechanical filter wheel, while mechanical shutters alternated illumination with the respective lasers, similar to a previously described method^58. Channels were as follows: mtagBFP2 was imaged using a 405-nm laser and a Semrock FF01-440/40 emission filter; CyOFP1.5 was imaged using a 505-nm laser and a Semrock 609/54 emission filter; tagRFP-T was imaged using a 561-nm laser and a Semrock 609/54-nm emission filter; and mNeptune2.5 was imaged using a 561-nm laser and a Semrock 732/68-nm emission filter.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 844, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c2c27009-aa94-46b6-a8ab-0d7d62de19e9": {"__data__": {"id_": "c2c27009-aa94-46b6-a8ab-0d7d62de19e9", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.11, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b8129993-1a79-40bd-88ca-97b520bf2b72", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.11, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "e1da765eba6d739e7535bb24bce4cd6ea9764be0e38b4f3b71c9663cc5c9a3c9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "After the functional connectivity recording was complete, neuron identities were manually assigned by comparing each neuron\u2019s colour, position and size to a known atlas. Some neurons are particularly hard to identify in NeuroPAL and are therefore absent or less frequently identified in our recordings. Some neurons have dim tagRFP-T expression, which makes it difficult for the neuron segmentation algorithm to find them and, therefore, to extract their calcium activity. These neurons include, for example, AVB, ADF and RID. RID\u2019s distinctive position and its expression of CyOFP allowed us nevertheless to manually target it optogenetically. Neurons in the ventral ganglion are hard to identify because it appears as very crowded when viewed in the most common orientation that worms assume when mounted on a microscope slide. Neurons in the ventral ganglion are therefore sometimes difficult to distinguish from one another, especially for dimmer neurons such as the SIA, SIB and RMF neurons. In our strain, the neurons AWCon and AWCoff were difficult to tell apart on the basis of colour information.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1105, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "55f8a123-1d7c-4edf-879d-b90c3b7f092d": {"__data__": {"id_": "55f8a123-1d7c-4edf-879d-b90c3b7f092d", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.11, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "91bbac87-158d-4e3c-9099-be418dfa868c", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.11, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "fd295a501ccd2b4008534c0d88487fc4f9fe57c29667b4b295f3738cb99882d1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Volumetric image acquisition", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 31, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "302ac24a-40fb-4e69-a5bd-a2152f3f89fc": {"__data__": {"id_": "302ac24a-40fb-4e69-a5bd-a2152f3f89fc", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.11, para 5](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "219abecc-9fc0-4dfd-8027-086288a9f1e8", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.11, para 5](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "63265adfcc51ac59a35d1e62b8a98cf5091ac24211935b3663528da4b5d798ef", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Neural activity was recorded at whole-brain scale and cellular resolution through continuous acquisition of volumetric images in the red and green channels with a spinning disk confocal unit and using LabView software (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 219, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7014e566-2307-4f2a-ae89-814542f3ec00": {"__data__": {"id_": "7014e566-2307-4f2a-ae89-814542f3ec00", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.11, para 6](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "202fb7a8-8ae7-41be-b4fb-9d3167d7b267", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.11, para 6](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "4095645ae55f9f4278eca05cf135adaf51db381adb76fec033301c45fcc3e09f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "), similarly to a previous study^67, with a few upgrades. The imaging focal plane was scanned through the brain of the worm remotely using an electrically tunable lens (Optotune EL-16-40-TC) instead of moving the objective. The use of remote focusing allowed us to decouple the z-position of the imaging focal plane and that of the optogenetics two-photon spot (described below).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 379, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5dde8904-8186-4fd9-937d-cdc95d2a3957": {"__data__": {"id_": "5dde8904-8186-4fd9-937d-cdc95d2a3957", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.11, para 7](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "24de8744-1bb2-41a2-93cc-af4bb8493511", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.11, para 7](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "c19ec8097cdb845ff29701f4e9ec211080e4205be57257111efd9e9d14570ae6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Images were acquired by an sCMOS camera, and each acquired image frame was associated to the focal length of the tunable lens (z-position in the sample) at which it was acquired. To ensure the correct association between frames and z-position, we recorded the analogue signal describing the focal length of the tunable lens at time points synchronous with a trigger pulse output by the camera. By counting the camera triggers from the start of the recording, the z-positions could be associated to the correct frame, bypassing unknown operating-system-mediated latencies between the image stream from the camera and the acquisition of analogue signals.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 652, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cdced5d2-cd59-4aa1-a632-c6e881b12c33": {"__data__": {"id_": "cdced5d2-cd59-4aa1-a632-c6e881b12c33", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.11, para 8](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f11cc97a-3008-4a37-8cbd-d6e956ad5879", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.11, para 8](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "e9f332dddb19c30b9fcdebe4cda9d2126273f7085c048c2d4dce80fe378d6ae4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In addition, real-time \u2018pseudo\u2019-segmentation of the neurons (described below) required the ability to separate frames into corresponding volumetric images in real time. Because the z-position was acquired at a low sample rate, splitting of volumes on the basis of finite differences between successive z-positions could lead to errors in assignment at the edge of the z-scan. An analogue OP-AMP-based differentiator was used to independently detect the direction of the z-scan in hardware.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 489, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "bfaf96d2-d71e-459a-8f6e-d2f1a3817911": {"__data__": {"id_": "bfaf96d2-d71e-459a-8f6e-d2f1a3817911", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.11, para 9](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "38780606-9ba3-4675-9f26-41c75de0fa93", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.11, para 9](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "600320332cd8dcdf681eb0956c9520a965f727bd30dd9de5dbd529c4c4820d07", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Calcium imaging", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 18, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0d047c8c-9756-429c-97b7-3a530e5765e9": {"__data__": {"id_": "0d047c8c-9756-429c-97b7-3a530e5765e9", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.11, para 10](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6cb5ad16-ffdb-4779-900c-1bd9b11e3a0e", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.11, para 10](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "ff55af525a9cd449d0278d6a278f2083faf3b9e2ac90223eb9c74a2ee1ba1089", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Calcium imaging was performed in a single-photon regime with a 505-nm excitation laser through spinning disk confocal microscopy, at 2 vol s^\u22121. For functional connectivity experiments, an intensity of 1.4 mW mm^\u22122 at the sample plane was used to image GCaMP6s, well below the threshold needed to excite the GUR-3/PRDX-2 optogenetic system^24. We note that at this wavelength and intensity, animals exhibited very little spontaneous calcium activity.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 450, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ad642650-80da-4eec-8f35-7147d3ab8c9d": {"__data__": {"id_": "ad642650-80da-4eec-8f35-7147d3ab8c9d", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.11, para 11](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1921a4da-d097-46e1-8832-ce1799435f8c", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.11, para 11](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "3abc22b6deb2d0d892fe9279a50d3bb423a1fc234af4fc5e5cb4f0dd9779a112", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "For certain analyses (Fig. 6), recordings with ample spontaneous activity were desired. In those cases, we increased the 505-nm intensity sevenfold, to approximately 10 mW mm^\u22122, and recorded from AML320 strains that lacked exogenous GUR-3/PRDX-2 to avoid potential widespread neural activation. Under these imaging conditions, we observed population-wide slow stereotyped spontaneous oscillatory calcium dynamics, as previously reported^35,68.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 444, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ea3d18c6-4d86-42be-aa6a-50d12e08bcf2": {"__data__": {"id_": "ea3d18c6-4d86-42be-aa6a-50d12e08bcf2", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.11, para 12](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "27976bac-3aba-4f26-8acc-b3658fca4d2d", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.11, para 12](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "57681ff5300b78d46f2f79bd1a01a48be91abd8518cd96881405e6776b4cc555", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Extraction of calcium activity from the images", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 49, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "758395dd-6f7a-4a20-b67c-b632b4a89e69": {"__data__": {"id_": "758395dd-6f7a-4a20-b67c-b632b4a89e69", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.11, para 13](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c8b14fda-fa2a-4145-86eb-35d5e3073a94", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.11, para 13](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "c297fd495012c94da168e9c6f25f57c9140b6876a30380ac98c9eddde84c17a5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Calcium activity was extracted from the raw images by using Python libraries implementing optimized versions of a previously described algorithm^69, available at", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 161, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d9ca9905-5cf0-43b2-9ffe-1598eb3782e3": {"__data__": {"id_": "d9ca9905-5cf0-43b2-9ffe-1598eb3782e3", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.11, para 14](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f44d6929-18ee-42f8-bc39-3e5a3f726d66", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.11, para 14](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "30ae3e76f8ebace5cb30f9ce27e977620fef185607e6173e43bf0252571b8094", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ",", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "633abfe7-d05d-4169-aae8-c50435dec4c5": {"__data__": {"id_": "633abfe7-d05d-4169-aae8-c50435dec4c5", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.11, para 15](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "101902cb-84ae-4b7c-bd1a-93e4b3077c93", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.11, para 15](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "f88868bbe0697717fb6446778fd35a35690d412bda4a2355188f19b552d9f453", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ",", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "151796a4-f967-4759-9fc3-78aacd8ebaa5": {"__data__": {"id_": "151796a4-f967-4759-9fc3-78aacd8ebaa5", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.11, para 17](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d6616992-247c-4057-b692-e49293200fa4", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.11, para 17](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "f4e003fe9d4fd13dd9b827b84b982f11664081ae48a87238fe747a615c18a9e0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ".", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "55bb1da1-69ce-457f-a001-da086d92ccd7": {"__data__": {"id_": "55bb1da1-69ce-457f-a001-da086d92ccd7", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.11, para 18](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "54c5c9b3-0e8c-41bd-8414-619805d7e764", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.11, para 18](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "fd10d0626035bdbf6bb5de4fea0e1b78dc0f01e2f6df79204b6cbd5742c45fc3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The positions of neurons in each acquired volume were determined by computer vision software implemented in C++. This software was greatly optimized to identify neurons in real time, to also enable closed-loop targeting and stimulus delivery (as described in \u2018Stimulus delivery and pulsed laser\u2019). Two design choices made this algorithm considerably faster than previous approaches. First, a local maxima search was used instead of a slower watershed-type segmentation. The nuclei of *C. elegans* neurons are approximately spheres and so they can be identified and separated by a simple local maxima search. Second, we factorized the three-dimensional (3D) local maxima search into multiple two-dimensional (2D) local maxima searches. In fact, any local maximum in a 3D image is also a local maximum in the 2D image in which it is located. Local maxima were therefore first found in each 2D image separately, and then candidate local maxima were discarded or retained by comparing them to their immediate surroundings in the other planes. This makes the algorithm less computationally intensive and fast enough to also be used in real time. We refer to this type of algorithm as \u2018pseudo\u2019-segmentation because it finds the centre of neurons without fully describing the extent and boundaries of each neuron.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1306, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "43c9dcf4-0c87-4d84-b7da-2fff74f3899d": {"__data__": {"id_": "43c9dcf4-0c87-4d84-b7da-2fff74f3899d", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.11, para 19](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9b417ae4-9063-48ed-82ec-628655b06856", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.11, para 19](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "feb71019bd3d81222a1a1b25bc0e72be673eccfcdb410977bfd55cb6bf038368", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "After neural locations were found in each of the volumetric images, a nonrigid point-set registration algorithm was used to track their locations across time, matching neurons identified in a given 3D image to the neurons identified in a 3D image chosen as reference. Even worms that are mechanically immobilized still move slightly and contract their pharynx, thereby deforming their brain and requiring the tracking of neurons. We implemented in C++ a fast and optimized version of the Dirichelet\u2013Student\u2019s-t mixture model (DSMM)^70.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 535, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9507f8ac-b04e-4eff-abc7-e8c3da12ceec": {"__data__": {"id_": "9507f8ac-b04e-4eff-abc7-e8c3da12ceec", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.11, para 20](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f23ccd65-ea75-4cee-bd7b-d4aae4f638d0", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.11, para 20](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "58cd2c7173328412b8e6c0a39c0c5e5357a663f5f82944b834f26ae2441e149d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Calcium pre-processing", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 25, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "aa7778f0-7786-4c6f-be19-104fb322784e": {"__data__": {"id_": "aa7778f0-7786-4c6f-be19-104fb322784e", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.11, para 21](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8aee67bc-485b-4458-8c88-b5e2116fe7ba", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.11, para 21](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "b3c9c8cddd5ad6b16a8a82c33e6e2a0160389207c91acb4e1a9a006d58f610a7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The GCaMP6s intensity extracted from the images undergoes the following pre-processing steps. (1) Missing values are interpolated on the basis of neighbouring time points. Missing values can occur when a neuron cannot be identified in a given volumetric image. (2) Photobleaching is removed by fitting a double exponential to the baseline signal. (3) Outliers more than 5 standard deviations away from the average are removed from each trace. (4) Traces are smoothed using a causal polynomial filtering with a window size of 6.5 s and polynomial order of 1 (Savitzky\u2013Golay filters with windows completely \u2018in the past\u2019; for example, obtained with scipy.signal.savgol\\_coeffs(window\\_length=13, polyorder=1, pos=12)). This type of filter with the chosen parameters is able to remove noise without smearing the traces in time. Note that when fits are performed (for example, to calculate kernels), they are always performed on the original, non-smoothed traces.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 959, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c3aa1740-d0ef-4512-be97-f9e22edce2d4": {"__data__": {"id_": "c3aa1740-d0ef-4512-be97-f9e22edce2d4", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.12, para 0](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "48ed15d5-2a8f-459f-a5f2-8de31c94780d", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.12, para 0](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "f668509c65218ca27bff89d9f05e218676d82e0608bdf812da32b1cb797a0d06", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "(5) Where \\Delta F/F\\_0 of responses is used, F\\_0 is defined as the value of F in a 30-s interval before the stimulation time and \\Delta F \\equiv F - F\\_0. In Fig. 2a, for example, \\_t refers to the mean over a 30-s post-stimulus window.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 238, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f3e782f0-c6bc-48fe-afde-d177f2ffc957": {"__data__": {"id_": "f3e782f0-c6bc-48fe-afde-d177f2ffc957", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.12, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "24fb2399-7f9f-4f2c-b47f-7f925c9cad83", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.12, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "7d620a17505cc0fafed6957e6b17656e7144b410f840bbff437e5ed704a1b7c5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Stimulus delivery and pulsed laser", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 37, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "114f4099-b7bb-4599-8063-88d2ecce9d4c": {"__data__": {"id_": "114f4099-b7bb-4599-8063-88d2ecce9d4c", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.12, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "15a9695f-280d-455d-a3d9-261950f6c129", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.12, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "eac56ad32d7dfb20095b2bb9633aa794d81c2aa43abff81075319d31ba9ec76a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "For two-photon optogenetic targeting, we used an optical parametric amplifier (OPA; Light Conversion ORPHEUS) pumped by a femtosecond amplified laser (Light Conversion PHAROS). The output of the OPA was tuned to a wavelength of 850 nm, at a 500 kHz repetition rate. We used temporal focusing to spatially restrict the size of the two-photon excitation spot along the microscope axis. A motorized iris was used to set its lateral size. For temporal focusing, the first-order diffraction from a reflective grating, oriented orthogonally to the microscope axis, was collected (as described previously^71) and travelled through the motorized iris, placed on a plane conjugate to the grating. To arbitrarily position the two-photon excitation spot in the sample volume, the beam then travelled through an electrically tunable lens (Optotune EL-16-40-TC, on a plane conjugate to the objective), to set its position along the microscope axis, and finally was reflected by two galvo-mirrors to set its lateral position. The pulsed beam was then combined with the imaging light path by a dichroic mirror immediately before entering the back of the objective.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1149, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "66dcef40-c79f-4252-a316-eac39fe5895b": {"__data__": {"id_": "66dcef40-c79f-4252-a316-eac39fe5895b", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.12, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bcbefbbf-61ea-4d0c-ba55-2b449a48476a", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.12, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "6cb97e41cb1c56ff20e6db367e5e1d91b9cdb2268089bd4752a9406c356bf11d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Most of the stimuli were delivered automatically by computer control. Real-time computer vision software found the position of the neurons for each volumetric image acquired, using only the tagRFP-T channel. To find neural positions, we used the same pseudo-segmentation algorithm described above. The algorithm found neurons in each 2D frame in around 500 \\mus as the frames arrived from the camera. In this way, locations for all neurons in a volume were found within a few milliseconds of acquiring the last frame of that volume.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 532, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e67802f9-3d7d-45e4-a31b-e05d512c72f0": {"__data__": {"id_": "e67802f9-3d7d-45e4-a31b-e05d512c72f0", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.12, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0d99e0e5-46f2-4513-b815-cc39a30f4485", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.12, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "c7eebaa07b34a37d2488eaad6fa5bbbab1c8f5ef0be2e17ebd25327ccb4eca7d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Every 30 s, a random neuron was selected among the neurons found in the current volumetric image, on the basis of only its tagRFP-T signal. After galvo-mirrors and the tunable lens set the position of the two-photon spot on that neuron, a 500-ms (300-ms for the unc-31-mutant strain) train of light pulses was used to optogenetically stimulate that neuron. The duration of stimulus illumination for the unc-31-mutant strain was selected to elicit calcium transients in stimulated neurons with a distribution of amplitudes such that the maximum amplitude was similar to those in WT-background animals, (Extended Data Fig. 2f). The output of the laser was controlled through the external interface to its built-in pulse picker, and the power of the laser at the sample was 1.2 mW at 500 kHz. Neuron identities were assigned to stimulated neurons after the completion of experiments using NeuroPAL^27.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 898, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "795cc04b-3a16-4a00-9a81-c87628f8cf75": {"__data__": {"id_": "795cc04b-3a16-4a00-9a81-c87628f8cf75", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.12, para 5](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0713fd6b-5e04-4d2b-86bc-f9c1b6a423d2", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.12, para 5](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "e21e4145a6000f934b0a2a5a3c814fb471fb404a6a270ba69282e1a457a972df", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "To probe the AFD\u2192AIY neural connection, a small set of stimuli used variable pulse durations from 100 ms to 500 ms in steps of 50 ms selected randomly to vary the amount of optogenetic activation of AFD. In some cases, neurons of interest were too dim to be detected by the real-time software. For those neurons of interest, additional recordings were performed in which the neuron to be stimulated was manually selected on the basis of its colour, size and position. This was the case for certain stimulations of neurons RID and AFD.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 534, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8bcc11e6-ecd7-4ac9-86cf-3c90db321089": {"__data__": {"id_": "8bcc11e6-ecd7-4ac9-86cf-3c90db321089", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.12, para 6](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "99b9281e-b457-42a4-817f-b9daf2ae65fb", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.12, para 6](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "58ee6323ab5251d09e7e07f76da3cc3dd41b86582f080e7bf8bdfaae71703275", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Characterization of the size of the two-photon excitation spot", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 65, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "80c7b4fd-8914-40fb-a2aa-bc1cb1e9d273": {"__data__": {"id_": "80c7b4fd-8914-40fb-a2aa-bc1cb1e9d273", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.12, para 7](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6f49fc24-0bf9-4273-962c-f850aabebbf0", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.12, para 7](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "9daefd71ae365015ddd53c20b94e384442046a64bb162912e7f07d81cefb6c8b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The lateral (xy) size of the two-photon excitation spot was measured with a fluorescent microscope slide, and the axial (z) size was measured using 0.2-nm fluorescent beads (Suncoast Yellow, Bangs Laboratories), by scanning the z-position of the optogenetic spot while maintaining the imaging focal plane fixed (Extended Data Fig. 2a).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 335, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1e0880a3-db7b-48cf-a9fc-c0a17b412e80": {"__data__": {"id_": "1e0880a3-db7b-48cf-a9fc-c0a17b412e80", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.12, para 8](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "17dc4f65-e93b-481b-a8cc-0496c68e1aef", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.12, para 8](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "ea63dc1ccd00cca0604773a41048572e1600b2ea5327e8e8ef7a2d9e11d68351", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We further tested our targeted stimulation in two ways: selective photobleaching and neuronal activation. First, we targeted individual neurons at various depths in the worm\u2019s brain, and we illuminated them with the pulsed laser to induce selective photobleaching of tagRFP-T. Extended Data Fig. 2c,d shows how our two-photon excitation spot selectively targets individual neurons, because it photobleaches tagRFP-T only in the neuron that we decide to target, and not in nearby neurons. To faithfully characterize the spot size, we set the laser power such that the two-photon interaction probability profile of the excitation spot would not saturate the two-photon absorption probability of tagRFP-T. Second, we showed that our excitation spot is restricted along the z-axis by targeting a neuron and observing its calcium activity. When the excitation was directed at the neuron but shifted by 4 \\mum along z, the neuron showed no activation. By contrast, the neuron showed activation when the spot was correctly positioned on the neuron (Extended Data Fig. 2e). To further show that our stimulation is spatially restricted to an individual neuron more broadly throughout our measurements, we show that stimulations do not elicit responses in most of the close neighbours of the targeted neurons (Extended Data Fig. 2i and Supplementary Information).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1353, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "148d6097-e369-47cb-80ed-8f4324c4754d": {"__data__": {"id_": "148d6097-e369-47cb-80ed-8f4324c4754d", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.12, para 9](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f9851154-2c60-4f5c-9871-2c649f91b3d5", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.12, para 9](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "f6e3ccffc8910f170cf049c72b0bfbfcda60ddfb18d166226969b72e2258f767", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Inclusion criteria", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 21, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "35739bd1-7537-49d4-a73f-473cc0f66c98": {"__data__": {"id_": "35739bd1-7537-49d4-a73f-473cc0f66c98", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.12, para 10](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7615c084-aa7a-423f-93ce-4fc9ad5af5f1", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.12, para 10](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "8079147f19bb7f3510e6b190081a76d46b6913f2c8c0c0196f2ce446db8e63fb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Stimulation events were included for further analysis if they evoked a detectable calcium response in the stimulated neuron (autoresponse). A classifier determined whether the response was detected by inspecting whether the amplitude of both the \\Delta F/F\\_0 transient and its second derivative exceeded a pair of thresholds. The same threshold values were applied to every animal, strain, neuron and stimulation event, and were originally set to match the human perception of a response above noise. Stimulation events that did not meet both thresholds for a contiguous 4 s were excluded. The RID responses shown in Fig. 4 and Extended Data Fig. 7c are an exception to this policy. RID is visible on the basis of its CyOFP expression, but its tagRFP-T expression is too dim to consistently extract calcium signals. Therefore, in Fig. 4 and Extended Data Fig. 7c (but not in other figures, such as Fig. 2), downstream neurons\u2019 responses to RID stimulation were included even in cases in which it was not possible to extract a calcium-activity trace in RID.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1057, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0b953fc9-1fab-40ac-a686-015df06dc531": {"__data__": {"id_": "0b953fc9-1fab-40ac-a686-015df06dc531", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.12, para 11](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "95c0c892-31f5-45fb-b910-992277afa508", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.12, para 11](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "c7c0b36c6707dc3c4a8443b758b3141b0e4ea6f0cb4eebbe276a22cebe3a5078", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Neuron traces were excluded from analysis if a human was unable to assign an identity or if the imaging time points were absent in a contiguous segment longer than 5% of the response window owing to imaging artefacts or tracking errors. A different policy applies to dim neurons of interest that are not automatically detected by the pseudo-segmentation algorithm in the 3D image used as reference for the point-set registration algorithm. In those cases, we manually added the position of those neurons to the reference 3D image. If these \u2018added\u2019 neurons are automatically detected in most of the other 3D images, then a calcium activity trace can be successfully produced by the DSMM nonrigid registration algorithm, and is treated as any other trace. However, if the \u2018added\u2019 neurons are too dim to be detected also in the other 3D images and the calcium activity trace cannot be formed for more than 50% of the total time points, the activity trace for those neurons is extracted from the neuron\u2019s position as determined from the position of neighbouring neurons. In the analysis code, we refer to these as \u2018matchless\u2019 traces, because the reference neuron is not matched to any detected neuron in the specific 3D image, but its position is just transformed according to the DSMM nonrigid deformation field. In this way, we are able to recover the calcium activity of some neurons whose tagRFP-T expression is otherwise too dim to be reliably detected by the pseudo-segmentation algorithm. Responses to RID stimulation shown in Fig. 4 and Extended Data Fig. 7c are an exception to this policy. In these cases, the activity of any neuron for which there is not a trace for more than 50% of the time points is substituted with the corresponding \u2018matchless\u2019 trace, and not just for the manually added neurons. This is important to be able to show responses of neurons such as ADL, which have dim tagRFP-T expression. In the RID-specific case, to exclude responses that become very large solely because of numerical issues in the division by the baseline activity owing to the dim tagRFP-T, we also introduce a threshold excluding \\Delta F/F > 2.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2144, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "df89e394-ead8-477f-8f62-134ffcf5808a": {"__data__": {"id_": "df89e394-ead8-477f-8f62-134ffcf5808a", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.13, para 0](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "167fa6b5-89d3-419a-8a9b-113af81d40a4", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.13, para 0](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "223f129877157bd87e7ed23ce63d77921a7ecec5132adb46509f4881e932499a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Article", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 9, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e98c54e0-4db9-4526-a50f-2d207c78190e": {"__data__": {"id_": "e98c54e0-4db9-4526-a50f-2d207c78190e", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.13, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2bd708b1-adce-4d19-8437-d87e7b089263", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.13, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "d6b9b5dac2cae7a43dfa0cb8d67414cdf3ee017b6646baf11dad682afeeb6f44", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Kernels were computed only for stimulation-response events for which the automatic classifier detected responses in both the stimulated and the downstream neurons. If the downstream neuron did not show a response, we considered the downstream response to be below the noise level and the kernel to be zero.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 306, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d12f0680-20cf-4f79-8b9d-ebb0976df2e5": {"__data__": {"id_": "d12f0680-20cf-4f79-8b9d-ebb0976df2e5", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.13, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "659b7c50-e06a-48a5-a5c5-1368ee525f2c", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.13, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "0e13b3440db799956803fd6be1768d76e7bfeeccc43ae34c6ae9b449510dca95", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Statistical analysis", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 23, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "acf6d841-7dfd-43f2-a14e-94659fe7467b": {"__data__": {"id_": "acf6d841-7dfd-43f2-a14e-94659fe7467b", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.13, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e311df90-c260-4a70-af0a-beb75c5f8aff", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.13, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "e56f9c769c336f4ea7a22ef52f955b7e71c0d1f8fce7f097358e2cd47d55e760", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We used two statistical tests to identify neuron pairs that under our stimulation and imaging conditions can be deemed \u2018functionally connected\u2019, \u2018functionally non-connected\u2019 or for which we lack the confidence to make either determination. Both tests compare observed calcium transients in each downstream neuron to a null distribution of transients recorded in experiments lacking stimulation.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 394, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "96889f20-ebac-4fa3-b534-af53769964ef": {"__data__": {"id_": "96889f20-ebac-4fa3-b534-af53769964ef", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.13, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "24b880ed-d191-4ccb-8d3e-d67a30cb232c", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.13, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "64db1c8bec5d20909e00c74e58a9482bd609136f60463ebdcbca60a21c5af81c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "To determine whether a pair of neurons can be deemed functionally connected, we calculated the probability of observing the measured calcium response in the downstream neuron given no neural stimulation. We used a two-sided Kolmogorov\u2013Smirnov test to compare the distributions of the downstream neuron\u2019s \\Delta F/F\\_0 amplitude and its temporal second derivative from all observations of that neuron pair under stimulation to the empirical null distributions taken from control recordings lacking stimulation. P values were calculated separately for \\Delta F/F\\_0 and its temporal second derivative, and then combined using Fischer\u2019s method to report a single fused P value for each neuron pair. Finally, to account for the large number of hypotheses tested, a false discovery rate was estimated. From the list of P values, each neuron was assigned a q value using the Storey\u2013Tibshirani method^40. q values are interpreted as follows: when considering an ensemble of putative functional connections of q values all less than or equal to q\\_c, an approximately q\\_c fraction of those connections would have appeared in a recording that lacked any stimulation.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1158, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7f6ae023-22e2-47bf-bdb2-25b686a440da": {"__data__": {"id_": "7f6ae023-22e2-47bf-bdb2-25b686a440da", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.13, para 5](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f3241846-9b79-4e12-ab65-eff94bf5d324", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.13, para 5](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "18dcdde04576ab317d355a0b0f787628811ed6732ca84a1ad5977d09dcc33ba2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "To explicitly test whether a pair of neurons are functionally not connected, taking into account the amplitude of the response, their reliability, the number of observations and multiple hypotheses, we also computed equivalence P\\_eq and q\\_eq values. This assesses the confidence of a pair not being connected. We test whether our response is equivalent to what we would expect from our control distribution using the two one-sided t-test (TOST)^72. We computed P\\_eq values for \\Delta F/F\\_0 and its temporal second derivative for a given pair being equivalent to the control distributions within an \\epsilon = 1.2\\sigma\\_\\Delta F/F\\_0, \\partial\\_t^2. Here, \\sigma\\_\\Delta F/F\\_0, \\partial\\_t^2 is the standard deviation of the corresponding control distribution. We then combined the two P\\_eq values into a single one with the Fisher method and computed q\\_eq values using the Storey\u2013Tibshirani method^40. Note that, different from the regular P values described above, the equivalence test relies on the arbitrary choice of \\epsilon, which defines when we call two distributions equivalent. We chose a conservative value of \\epsilon = 1.2\\sigma.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1150, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0ee04169-9e5b-4736-834b-c15ac97bc0d5": {"__data__": {"id_": "0ee04169-9e5b-4736-834b-c15ac97bc0d5", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.13, para 6](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1df0a608-3aee-40ca-88ac-6fa8c2723fb1", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.13, para 6](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "4366eccd5a1ee4949d9aefead01b6952347cf62537ebd468d9731ffa3b11da18", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We note that the statistical framework is stringent and a large fraction of measured neuron pairs fail to pass either statistical test.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 135, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b921a50c-6508-411d-aa01-fea7b1c54f5c": {"__data__": {"id_": "b921a50c-6508-411d-aa01-fea7b1c54f5c", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.13, para 7](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b2623878-c8c4-45ab-a5c2-1998291bf6d3", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.13, para 7](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "97da79a98a5b6e4c9417d61e359fabda34abec0ae9af8d46c3a9b913b63ebd49", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Measuring path length through the synaptic network", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 53, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6eebd81e-39c6-4d0d-b7f0-92d8d61f8325": {"__data__": {"id_": "6eebd81e-39c6-4d0d-b7f0-92d8d61f8325", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.13, para 8](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e80f72ba-ae2c-437b-99ec-160eaa318695", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.13, para 8](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "e6233f2b88eb04667a9ce34e5e8e3831bdfb01b6a6b8af6eba89427774db2b8f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "To find the minimum path length between neurons in the anatomical network topology, we proceeded iteratively. We started from the original binary connectome and computed the map of strictly two-hop connections by looking for pairs of neurons that are not connected in the starting connectome (the actual anatomical connectome at the first step) but that are connected through a single intermediate neuron. To generate the strictly three-hop connectome, we repeated this procedure using the binary connectome including direct and two-hop connections, as the starting connectome. This process continued iteratively to generate the strictly n-hop connectome.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 655, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1dca2a62-99ea-40e7-85c2-599b6e15abf6": {"__data__": {"id_": "1dca2a62-99ea-40e7-85c2-599b6e15abf6", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.13, para 9](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c381969a-dcab-4dc8-b17d-c02954184083", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.13, para 9](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "70604c638aa2a06638450d6077179fb43585709463fc1875bdda47472e8d46fc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In the anatomical connectome (the starting connectome for the first step in the procedure above), a neuron was considered to be directly anatomically connected if the connectomes of any of the four L4 or adult individuals in refs. 1 and 6 contained at least one synaptic contact between them. Note that this is a permissive description of anatomical connections, as it considers even neurons with only a single synaptic contact in only one individual to be connected.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 467, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "99441386-cd13-45d4-a772-b24fc7019188": {"__data__": {"id_": "99441386-cd13-45d4-a772-b24fc7019188", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.13, para 10](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5e0961c2-b05a-4413-8981-612290f802c9", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.13, para 10](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "7822e528829fceb44a52b38d552d9b559b77d2033c4985389c3595479848c3bc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Fitting kernels", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 18, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "01b80eac-3e24-4588-acef-244fdb2cbfe6": {"__data__": {"id_": "01b80eac-3e24-4588-acef-244fdb2cbfe6", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.13, para 11](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ea102bf7-9161-43b9-b5ae-ed7d1492cf03", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.13, para 11](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "faa6f9bb18743d199ff95919248399db02adc7c7eb7d7c5662b35216a302af73", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Kernels k\\_ij(t) were defined as the functions to be convolved with the activity \\Delta F\\_j of the stimulated neuron to obtain the activity \\Delta F\\_i of a responding neuron i, such that \\Delta F\\_i(t) = (k\\_ij \\* \\Delta F\\_j)(t). To fit kernels, each kernel k(t) was parametrized as a sum of convolutions of decaying exponentials", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 332, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "931c3c5b-92b6-4f0d-8ac0-db2ec4f7313c": {"__data__": {"id_": "931c3c5b-92b6-4f0d-8ac0-db2ec4f7313c", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.13, para 12](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "64ea2107-4fd7-4ba9-9319-c529d70ffaed", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.13, para 12](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "3cc569f84c7ba4f25fe10a3ab109417caf21b31003e51399423404e2adbfe980", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "k(t) = \\sum\\_m c\\_m (\\theta(t)e^-\\gamma\\_m,0t) \\* (\\theta(t)e^-\\gamma\\_m,1t) \\* \\ldots,\n\\quad (1)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 97, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0afc8edc-c5b3-44a5-8776-e95f2fc263ea": {"__data__": {"id_": "0afc8edc-c5b3-44a5-8776-e95f2fc263ea", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.13, para 13](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0d46aa09-6277-42eb-94f0-8a44e19e787e", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.13, para 13](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "a5b63483bac060ceba6018887eed57fd9a8c4842d0938e646956b01b89af5d18", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "where the indices i,j are omitted for clarity and \\theta is the Heaviside function. This parametrization is exact for linear systems, and works as a description of causal signal transmission also in nonlinear systems. Note that increasing the number of terms in the successive convolutions does not lead to overfitting, as would occur by increasing the degree of a polynomial. Overfitting could occur by increasing the number of terms in the sum, which in our fitting is constrained to be a maximum of 2. The presence of two terms in the sum allows the kernels to represent signal transmission with saturation (with c\\_0 and c\\_1 of opposite signs) and assume a fractional-derivative-like shape.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 695, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cbcc3872-e9bf-4dc5-b8ae-154d5b627193": {"__data__": {"id_": "cbcc3872-e9bf-4dc5-b8ae-154d5b627193", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.13, para 14](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8feaf642-2fc5-48b5-8f8c-83454c064d15", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.13, para 14](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "19ae932cc2024c31d390342ff1f0efb182edce4825dc51d93392a606ef668332", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The convolutions are performed symbolically. The construction of kernels as in equation (1) starts from a symbolically stored, normalized decaying exponential kernel with a factor A, A\\gamma\\_0\\theta(t)e^-\\gamma\\_0t. Convolutions with normalized exponentials \\gamma\\_n\\theta(t)e^-\\gamma\\_nt are performed sequentially and symbolically, taking advantage of the fact that successive convolutions of exponentials always produce a sum of functions in the form \\propto \\theta(t)t^ne^-\\gamma t. Once rules are found to convolve an additional exponential with a function in that form, any number of successive convolution can be performed. These rules are as follows:", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 660, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "826ec851-3293-415a-b9f4-9b3b5176e243": {"__data__": {"id_": "826ec851-3293-415a-b9f4-9b3b5176e243", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.13, para 15](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "66da8778-18f6-42aa-baf3-b83632d94474", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.13, para 15](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "d7f46f5a9e6a4e505d67e61c0b46ba04939394c516efed5ab271e70707369aae", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "1. If the initial term is a simple exponential with a given factor (not necessarily just the normalization \\gamma) c\\_i\\theta(t)e^-\\gamma\\_it and \\gamma\\_i \\neq \\gamma\\_n, then the convolution is", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 195, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fc868917-bd94-4793-9f73-cb173e7daf32": {"__data__": {"id_": "fc868917-bd94-4793-9f73-cb173e7daf32", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.13, para 16](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ed4e063b-0e8b-4e36-9c58-77839929d907", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.13, para 16](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "0341e07a55ac42c8debe40592e2dd98838cbeb2cea550f0361ab397914357237", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "c\\_i\\theta(t)e^-\\gamma\\_it \\* \\gamma\\_n\\theta(t)e^-\\gamma\\_nt = c\\_\\mu\\theta(t)e^-\\gamma\\_\\mu t + c\\_\\nu\\theta(t)e^-\\gamma\\_\\nu t,\n\\quad (2)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 140, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2e7c67ab-6ba8-41db-8b1e-4fc0f293e75e": {"__data__": {"id_": "2e7c67ab-6ba8-41db-8b1e-4fc0f293e75e", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.13, para 17](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5e47118a-6c43-4f21-8d8e-d9d010ea619b", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.13, para 17](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "2a67b83ab4e2f863cf385c48b4e8f6a4ed9db8a33f66b75802a72a6e0d911a90", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "with c\\_\\mu = \\frac{c\\_i\\gamma\\_n}{\\gamma\\_n - \\gamma\\_i}, c\\_\\nu = -\\frac{c\\_i\\gamma\\_n}{\\gamma\\_n - \\gamma\\_i} and \\gamma\\_\\mu = \\gamma\\_i, \\gamma\\_\\nu = \\gamma\\_n.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 166, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "62d5ff05-8b38-4c94-afd7-f6034a6c5351": {"__data__": {"id_": "62d5ff05-8b38-4c94-afd7-f6034a6c5351", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.13, para 18](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d7b9cbd8-3da6-48dd-b9bc-edd557925a46", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.13, para 18](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "b43381d98da7314bcbc42c17ab3b2d6184d1f02e452c7c7036081a1241ab9705", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "2. If the initial term is a simple exponential and \\gamma\\_i = \\gamma\\_n, then", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 78, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1adf6c82-4d65-44f7-9181-a090b5760097": {"__data__": {"id_": "1adf6c82-4d65-44f7-9181-a090b5760097", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.13, para 19](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "09d42bd8-49c4-41b6-b37a-85455ff618eb", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.13, para 19](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "67e61c5d42a372f923d744e083025ea0807257897372ea97112fa0b5dae8407f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "c\\_i\\theta(t)e^-\\gamma\\_it \\* \\gamma\\_n\\theta(t)e^-\\gamma\\_nt = c\\_\\mu\\theta(t)te^-\\gamma\\_\\mu t,\n\\quad (3)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 107, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b21ff568-14d0-4914-894b-9ad0a2d9deed": {"__data__": {"id_": "b21ff568-14d0-4914-894b-9ad0a2d9deed", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.13, para 20](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "846dc1e3-87ae-4adb-af81-9bb411ed7ecf", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.13, para 20](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "f552d9bf695ee782ae4c8d591c00609ef67c94a1594946b583d1abeeebb70a85", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "with c\\_\\mu = c\\_i\\gamma\\_i and \\gamma\\_\\mu = \\gamma\\_i.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 56, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "599599df-0ab7-4c4b-8222-3afef8895dfb": {"__data__": {"id_": "599599df-0ab7-4c4b-8222-3afef8895dfb", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.13, para 21](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "96baac23-c698-4845-9f53-d71f2e6a3d46", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.13, para 21](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "733301c30667613a81a2edef33137f01771c7253805688822977c9331a07b28d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "3. If the initial term is a c\\_i\\theta(t)t^ne^-\\gamma\\_it term and \\gamma\\_i = \\gamma\\_\\mu, then", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 96, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "be5e8ce0-6cf6-4215-80fe-eb62d7de47d0": {"__data__": {"id_": "be5e8ce0-6cf6-4215-80fe-eb62d7de47d0", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.13, para 22](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "406089fb-b327-4ad3-9432-c97fb7dc6b25", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.13, para 22](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "abc70612750ad9ee367cac1feb5254a98c682715b659c7c8c43ce3b20d2ff8b3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "c\\_i\\theta(t)t^ne^-\\gamma\\_it \\* \\gamma\\_n\\theta(t)e^-\\gamma\\_nt = c\\_\\mu\\theta(t)t^n+1e^-\\gamma\\_\\mu t,\n\\quad (4)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 114, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5131eb3c-76d4-43c0-a980-8644219013ff": {"__data__": {"id_": "5131eb3c-76d4-43c0-a980-8644219013ff", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.13, para 23](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a3e9253f-a1c6-437f-9b71-2bc19c286c06", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.13, para 23](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "49da562ecc7cc6d0e10d2f550f77962a012e7e13da1ab6ef7772e9593fcf8add", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "with c\\_\\mu = \\frac{c\\_i\\gamma\\_i}{n+1} and \\gamma\\_\\mu = \\gamma\\_i.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 68, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "be9d1dac-6e43-403e-bea6-c75f71be8c44": {"__data__": {"id_": "be9d1dac-6e43-403e-bea6-c75f71be8c44", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.13, para 24](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "75f59e9c-895c-4a03-a218-9dce488bb4d7", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.13, para 24](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "a53f0174b008aa3c74c216b2e4c8ae77bf721b35129e5a16cadfbb5f5e09beca", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "4. If the initial term is a c\\_i\\theta(t)t^ne^-\\gamma\\_it term and \\gamma\\_i \\neq \\gamma\\_\\mu, then", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 99, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6281fcf3-a8c9-4686-8320-b5c1f2d3a5ad": {"__data__": {"id_": "6281fcf3-a8c9-4686-8320-b5c1f2d3a5ad", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.13, para 25](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bf9d03e9-edc3-4e2c-92d7-9c0040d9f9c6", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.13, para 25](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "c66126847e5e77953cff2c17c57013b5ef722eb7cf83217ddca8cd1b71966c0f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "c\\_i\\theta(t)t^ne^-\\gamma\\_it \\* \\gamma\\_n\\theta(t)e^-\\gamma\\_nt = c\\_\\mu\\theta(t)t^ne^-\\gamma\\_\\mu t + c\\_\\nu(\\theta(t)t^n-1e^-\\gamma\\_it \\* \\theta(t)e^-\\gamma\\_nt),\n\\quad (5)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 176, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7461cad4-0314-4fba-9797-f2aac0cc311c": {"__data__": {"id_": "7461cad4-0314-4fba-9797-f2aac0cc311c", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.13, para 26](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "52f2a96c-107b-4195-8b60-af399e4f3506", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.13, para 26](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "8868f5282a64ad88e0ac081606b0f47ba5704d969743e7e6c1bc8bf6e6b051d1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "where c\\_\\mu = \\frac{c\\_i\\gamma\\_n}{\\gamma\\_n - \\gamma\\_i}, \\gamma\\_\\mu = \\gamma\\_i, and c\\_\\nu = -n\\frac{c\\_i\\gamma\\_n}{\\gamma\\_n - \\gamma\\_i}.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 144, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8e6c7403-57ea-4e77-8266-a69ff4426496": {"__data__": {"id_": "8e6c7403-57ea-4e77-8266-a69ff4426496", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.13, para 27](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e13b278e-c728-4964-b6ed-4bc0f40120b7", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.13, para 27](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "58e14ff2346bf10dd3cd873e1b48235d5c908dbcba03e1f113234ffc4e655da7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Additional terms in the sum in equation (1) can be introduced by keeping track of the index m of the summation for every term and selectively convolving new exponentials only with the corresponding terms.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 204, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f7623bd5-ceac-4623-b871-f84bb3d60aeb": {"__data__": {"id_": "f7623bd5-ceac-4623-b871-f84bb3d60aeb", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.13, para 28](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a1a95b2b-c833-4d5a-a009-956163019cdb", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.13, para 28](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "1bbaf30bff5f37f8ae34d1f4b48a93c840952695424fcc7a6749f54be590037d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Kernel-based simulations of activity", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 39, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9dc87e27-7e37-44fe-aa48-cdaacb9b69c5": {"__data__": {"id_": "9dc87e27-7e37-44fe-aa48-cdaacb9b69c5", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.13, para 29](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "af332d9b-743c-4bab-8312-ca9d5a8ab1e5", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.13, para 29](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "9cb68484a8fabfbfdde746090497f8ba48d644a1c49030e0f4210f4909e08c82", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Using the kernels fitted from our functional data, we can simulate neural activity without making any further assumptions about the dynamical equations of the network of neurons. To compute the response of a neuron i to the stimulation of a neuron j, we simply convolve the kernel", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 280, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "18c17b0f-54d2-4683-8a64-99247a4075aa": {"__data__": {"id_": "18c17b0f-54d2-4683-8a64-99247a4075aa", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.14, para 0](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3bc1d30f-6a93-4eed-81ce-46f73ac37336", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.14, para 0](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "699811f721afe4fc8e48d391f48c43bc610cf427d2ca0bb7094c9bc132d39409", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# ki,j (t) with the activity \u0394Fj(t) induced by the stimulation in neuron j.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 75, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "407f6dcc-835f-4ee4-9e21-80476ee71f65": {"__data__": {"id_": "407f6dcc-835f-4ee4-9e21-80476ee71f65", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.14, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "55d13431-2bd3-4d8c-b54d-9d0129043989", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.14, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "3ea850c8322449e59ad940eb649a9b86dab0bfb91fa8b4f3f771cafd978ea51c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The positive or negative). The rise time was zero if the peak of the kernel was at time t\u2009=\u20090. However, saturation of the signal transmission can make kernels appear slower than the connection actually is. For example, the simplest instantaneous connection would be represented by a single decaying exponential in equation (1), which would have its peak at time t\u2009=\u20090. However, if that connection is saturating, a second, opposite-sign term in the sum is needed to fit the kernel. This second term would make the kernel have a later peak, thereby masking the instantaneous nature of the connection. To account for this effect of saturation, we removed terms representing saturation from the kernels and found the rise time of these \u2018non-saturating\u2019 kernels.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 757, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fc245c89-16a0-4342-a6dc-cf469121f070": {"__data__": {"id_": "fc245c89-16a0-4342-a6dc-cf469121f070", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.14, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3c49b67c-42ec-4723-a14b-871a73004ed8", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.14, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "9bd96f8627de971db1e8b2418c3fcfd97a944831cf9a1e7458a234c6539eaecb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# To compute kernel-derived neural activity correlations (Fig. 6), we completed the following steps.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 100, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "449c9d54-62b6-406e-9d8c-3f509da1534e": {"__data__": {"id_": "449c9d54-62b6-406e-9d8c-3f509da1534e", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.14, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "240f09b9-6d3f-4fc8-8205-3ca2c6382997", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.14, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "edc701dd39ad60a1acb314a2c423f34089f0d0340a71128fbc269e9bc3821bef", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "1. We computed the responses of all the neurons i to the stimulation of a neuron j chosen to drive activity in the network. To compute the responses, for each pair i, j, we used the kernel ki j (t)trials averaged over multiple trials. For kernel-based analysis, pairs with connections of q\u2009>\u20090.05 were considered not connected. We set the activity \u0394Fj(t) in the driving neuron to mimic an empirically observed representative activity transient.\n2. We computed the correlation coefficient of the resulting activities.\n3. We repeated steps 1 and 2 for a set of driving neurons (all or top-n neurons, as in Fig. 6).\n4. For each pair k, l, we took the average of the correlations obtained by driving the set of neurons j in step 3.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 727, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ec657f7f-0c0c-4778-a90a-754f9bdd307a": {"__data__": {"id_": "ec657f7f-0c0c-4778-a90a-754f9bdd307a", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.14, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ed103a00-f023-4d92-8576-aa6d79b1698d", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.14, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "083de0ae858bd5140ec099399389a30126f32ded80e2b2e888fd94565f913290", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Screen for purely extrasynaptic-dependent connections", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 55, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2be81d27-316f-4209-8c07-6b65281e78b2": {"__data__": {"id_": "2be81d27-316f-4209-8c07-6b65281e78b2", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.14, para 5](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "16ed9782-217f-413a-8bfd-20ced576394c", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.14, para 5](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "4c7f8fc3de640370e9b8a7617c6679112a4ef509f4fcf41221c15993ca168c95", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "To find candidate purely extrasynaptic-dependent connections, we considered the pairs of neurons that are connected in WT animals (qWT\u2009\u20090.05 to exclude very small responses that are nonetheless significantly different from the control distribution). We list these connections and provide additional examples in Extended Data Fig. 9.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 332, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "502bfe17-0fb6-47f7-8bb2-8b3fd1bffb46": {"__data__": {"id_": "502bfe17-0fb6-47f7-8bb2-8b3fd1bffb46", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.14, para 6](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d5a18d0d-3726-4e02-af9f-1affee0ac836", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.14, para 6](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "ee1fc821f8492c3a582f184e72aed68a7916ad681af33beb29cacec6dafdfe41", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Anatomy-derived simulations of activity", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 41, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3cc06f9a-1f7e-42f0-8ab2-da0e55819fae": {"__data__": {"id_": "3cc06f9a-1f7e-42f0-8ab2-da0e55819fae", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.14, para 7](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a8cf5ed5-dc1f-485b-9b31-96fbc6480b64", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.14, para 7](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "937869b00c9e8697a0b8e03d94befe422c369d2b32bf81c0fa510c023726080b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Anatomy-derived simulations were performed as described previously47. In brief, this simulation approach uses differential equations to model signal transmission through electrical and chemical synapses and includes a nonlinear equation for synaptic activation variables. We injected current in silico into individual neurons and simulated the responses of all the other neurons. Anatomy-derived responses (Fig. 3) of the connection from neuron j to neuron i were computed as the peak of the response of neuron i to the stimulation of j. Anatomy-based predictions of spontaneous correlations in Fig. 6 were calculated analogously to kernel-based predictions.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 658, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f97dcb05-615f-425f-96b4-98ad36e4ca17": {"__data__": {"id_": "f97dcb05-615f-425f-96b4-98ad36e4ca17", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.14, para 8](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "23f149f8-b0e5-49b9-9408-f4086bd35638", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.14, para 8](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "f8d9384685dc1910e52dfbb4ccc5396a3f556e355d972098ba0e1e44a7dfe03a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In one analysis in Fig. 3d, the synapse weights and polarities were allowed to float and were fitted from the functional measurements. In all other cases, synapse weights were taken as the scaled average of three adult connectomes1,6 and an L4 connectome6, and polarities were assigned on the basis of a gene-expression analysis of ligand-gated ionotropic synaptic connections that considered glutamate, acetylcholine and GABA neurotransmitter and receptor expression, as performed in a previous study37 and taken from CeNGEN38 and other sources. Specifically, we used a previously published dataset (S1 data in ref. 37) and aggregated polarities across all members of a cellular subtype (for example, polarities from source AVAL and AVAR were combined). In cases of ambiguous polarities, connections were assumed to be excitatory, as in the previous study37. For other biophysical parameters we chose values commonly used in C. elegans modelling efforts9,30,47,73.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 965, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e2d194c5-1cb4-4cb7-8432-bd084ed9f8a3": {"__data__": {"id_": "e2d194c5-1cb4-4cb7-8432-bd084ed9f8a3", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.14, para 9](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e16e5666-6eca-4c08-9f93-ac1de70f0d85", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.14, para 9](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "5a6dc660d586923e155b0121ef0bae21f51a9703d32776f836af316be44cb49b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Characterizing stereotypy of functional connections", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 53, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "92e9c8de-54e1-4d60-809e-0eb595a36082": {"__data__": {"id_": "92e9c8de-54e1-4d60-809e-0eb595a36082", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.14, para 10](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "967b3243-0f1a-4a38-9aad-61ac85a632b9", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.14, para 10](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "aad62729f6570d1f2725f6e2812f732aee763a71ddc661464ba09ba297a12b89", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "To characterize the stereotypy of a neuron pair\u2019s functional connection, its kernels were inspected. A kernel was calculated for every stimulus-response event in which both the upstream and downstream neuron exhibited activity that exceeded a threshold. At least two stimulus-response events that exceeded this threshold were required to calculate their stereotypy. The general strategy for calculating stereotypy was to convolve different kernels with the same stimulus inputs and compare the resulting outputs. The similarity of two outputs is reported as a Pearson\u2019s correlation coefficient. Kernels corresponding to different stimulus-response events of the same pair of neurons were compared with one another round-robin style, one round-robin each for a given input stimulus. For inputs we chose the set of all stimuli delivered to the upstream neuron. The neuron-pairs stereotypy is reported as the average Pearson\u2019s correlation coefficient across all round-robin kernel pairings and across all stimuli.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1010, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b447dae1-c4d0-4949-a6a4-132ed2d66249": {"__data__": {"id_": "b447dae1-c4d0-4949-a6a4-132ed2d66249", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.14, para 11](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8c9f0fbe-07f4-4e27-af2b-31fe8bb63d14", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.14, para 11](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "6e6a6073d8c83a4c273024601df87a0aa354ff5f9f5b929a046b26f105bf6159", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Rise time of kernels", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 22, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4a887e0d-3bb9-4d4c-be58-1a3036e915b0": {"__data__": {"id_": "4a887e0d-3bb9-4d4c-be58-1a3036e915b0", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.14, para 12](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0a0d49cf-6fec-4e34-9056-e174ff8cc5a7", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.14, para 12](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "a5f9f296bc2cdd721d4b230bfe10d32b8a0e8068cab15c01b3d3ee972e1bd066", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The rise time of kernels, shown in Fig. 5c and Extended Data Fig. 6d, was defined as the interval between the earliest time at which the value of the kernel was 1/e its peak value and the time of its peak (whether positive or negative).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 236, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5bc4806b-1469-441b-b322-2e01cca324b2": {"__data__": {"id_": "5bc4806b-1469-441b-b322-2e01cca324b2", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.14, para 13](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "adeeead2-8392-42eb-a051-a75a06e898e5", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.14, para 13](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "c13a90dbcc08af0daf1d69f64c371e7352cf389ff51bcb73a7ec36807996fa62", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Data availability", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 19, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "22f908cf-8730-4ff7-bbc5-1997da5c1d7b": {"__data__": {"id_": "22f908cf-8730-4ff7-bbc5-1997da5c1d7b", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.14, para 14](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b77ca4bd-b0a4-403c-9092-f4e34e8405ce", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.14, para 14](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "7573968eebd89973c4afbdda4ba35bd2cdcda628d6ba4b499fd5466688b601fd", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Machine-readable datasets containing the measurements from this work are publicly accessible through Open Science Foundation repository at", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 138, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "478b9b92-f795-4892-a216-a2cb9e5da24b": {"__data__": {"id_": "478b9b92-f795-4892-a216-a2cb9e5da24b", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.14, para 15](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6d0f201c-f68f-46a8-b800-8ba2760b42ec", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.14, para 15](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "0ad6594b1c0b2889312efbac3b2be6132c00211a12f213f4cdc8da0bec317d9c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ". Interactive browsable versions of the same data are available online at", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 73, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f5bfef8e-059d-491c-b775-7f23d4498030": {"__data__": {"id_": "f5bfef8e-059d-491c-b775-7f23d4498030", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.14, para 18](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8cd5d5f3-6eb3-4023-b59e-95acd7663660", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.14, para 18](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "4743dc735adc232634235c9f13b8649a3fab4d42baa3ba97389013b953597be0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ". Source data are provided with this paper.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 43, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "815c73bc-ccef-440c-8c1f-610437ab4aa2": {"__data__": {"id_": "815c73bc-ccef-440c-8c1f-610437ab4aa2", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.14, para 19](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ca85ed7e-4477-462d-b6ad-77b82a998bf9", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.14, para 19](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "e4ca9126fd0c45475be38e071c0cfde07d5cc61fafd489c4b7a67a09a562667a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Code availability", "mimetype": "text/plain", "start_char_idx": 0, 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Endocrinol.* **3**, 167 (2012).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2879, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d6e2f38c-6f01-4969-88d2-a7259ecc4563": {"__data__": {"id_": "d6e2f38c-6f01-4969-88d2-a7259ecc4563", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.15, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "063c7452-62bf-4a39-9d16-476142ece91c", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.15, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "6ba7c810015aa76c425b3dc1b7b1ceb42cbaaca793cf856501675bbbff67cef4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Acknowledgements** We thank J. Bien, A. Falkner, F. Graf Leifer, M. Murthy, E. Naumann, H. S. Seung and J. Shaevitz for comments on the manuscript. Online visualization software and hosting was created by research computing staff in the Lewis-Sigler Institute for Integrative Genomics and the Princeton Neuroscience Institute, with particular thanks to F. Kang, R. Leach, B. Singer, S. Heinicke and L. Parsons. Research reported in this work was supported by the National Institutes of Health National Institute of Neurological Disorders and Stroke under New Innovator award number DP2-NS116768 to A.M.L.; the Simons Foundation under award SCGB 543003 to A.M.L.; the Swartz Foundation through the Swartz Fellowship for Theoretical Neuroscience to F.R.; the National Science Foundation through the Center for the Physics of Biological Function (PHY-1734030); and the Boehringer Ingelheim Fonds to S.D. Strains from this work are being distributed by the CGC, which is funded by the NIH Office of Research Infrastructure Programs (P40 OD010440).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1045, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1d424128-0431-41b9-b77f-14959ca5503a": {"__data__": {"id_": "1d424128-0431-41b9-b77f-14959ca5503a", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.15, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b35ba401-2f7f-41d1-93c1-0be0f9a5a89a", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.15, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "e05b1d686f765e6004038be4a12022ce326eeba095a88ef308d8e794c79bed69", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Author contributions** A.M.L. and F.R. conceived the investigation. F.R., S.D. and A.M.L. contributed to the design of the experiments and the analytical approach. F.R. and S.D. conducted the experiments. A.K.S. designed and performed all transgenics. F.R. designed and built the instrument and the analysis framework and pipeline. F.R. and S.D. performed the bulk of the analysis with additional contributions from A.M.L. and A.K.S. All authors wrote and reviewed the manuscript. F.R. is currently at Regeneron Pharmaceuticals. 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Leifer.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 86, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b2514aa7-115a-4031-a352-b2667d9dd5c0": {"__data__": {"id_": "b2514aa7-115a-4031-a352-b2667d9dd5c0", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.15, para 9](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f7f51a01-6a63-41e2-9c43-3077c2309f3b", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.15, para 9](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "0cf1c3befc1d9b2ffacb38f18c3727220694358dc19cfe6919e7195ec4de9558", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Peer review information** Nature thanks Mei Zhen and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 144, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d6b62671-8d13-41f6-b296-5f6f378ffcec": {"__data__": {"id_": "d6b62671-8d13-41f6-b296-5f6f378ffcec", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.15, para 11](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "58d9fbdc-bd43-40d2-afef-7b5e186a6e2a", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.15, para 11](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "a632f7eb5111a04fb8d37e1906d59802324c7e6271cdc95ba608af542bf05c18", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ".", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9d67ceb6-9cd8-41de-833c-f5b6668287da": {"__data__": {"id_": "9d67ceb6-9cd8-41de-833c-f5b6668287da", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.16, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d82ce2d1-fc7a-4c82-9f37-de55929b647c", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.16, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "90f360cb7efb0cf7d69e7f49b03283fbd425ec4787ae8cb8e96917ee08be3c3a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Strain|Genotype|Expression|Role|Reference|\n|-|-|-|-|-|\n|AML320|\\*otIs669\\[NeuroPAL] V 14x; wtfIs145\\[pBX + rab-3::his-24::GCaMP6s::unc-54]\\*|NeuroPAL (Yemini et al., 2021); GCaMP6s in all neurons|Calcium imaging only, no activation.|(Yu et al., 2021)|\n|AML456|\\*wtfIs348 \\[pAS3-5xQUAS::\u0394pes-10P::AI::gur-3G::unc-54 75 ng/ul + pAS3-5xQUAS::\u0394pes-10P::AI::prdx-2G::unc-54 75 ng/ul + pAS-3-rab-3P::AI::QF+GR::unc-54 35 ng/ul + unc-122::GFP 100 ng/ul]\\*|GUR-3 + PRDX-2 in all neurons; GFP in coelomocytes|Optogenetic activator strain, used in creating AML462.|(Sharma et al., 2023) & this work|\n|AML462|\\*otIs669\\[NeuroPAL] V 14x; wtfIs145\\[pBX + rab-3::his-24::GCaMP6s::unc-54]; wtfIs348 \\[pAS3-5xQUAS:: \u0394pes-10P::AI::gur-3G::unc-54 75 ng/ul + pAS3-5xQUAS::\u0394pes-10P::AI::prdx-2G::unc-54 75 ng/ul + pAS-3-rab-3P::AI::QF+GR::unc-54 35 ng/ul + unc-122::GFP 100ng/ul]\\*|NeuroPAL (Yemini et al., 2021); GCaMP6s in all neurons; GUR-3 + PRDX-2 in all neurons; GFP in coelomocytes|Primary strain used for measuring signal propagatin.|(Sharma et al., 2023) & this work|\n|AML508|\\*unc-31(wtf502) IV; otIs669\\[NeuroPAL] V 14x; wtfIs145 \\[pBX + rab-3::his-24::GCaMP6s::unc-54]; wtfIs348 \\[pAS3-5xQUAS:: \u0394pes-10P::AI::gur-3G::unc-54 75 ng/ul + pAS3-5xQUAS:: \u0394pes-10P::AI::prdx-2G::unc-54 75 ng/ul + pAS-3-rab-3P::AI::QF+GR::unc-54 35 ng/ul + unc-122::GFP 100ng/ul]\\*|\\*unc-31\\* mutant background; NeuroPAL (Yemini et al., 2021); GCaMP6s in all neurons; GUR-3 + PRDX-2 in all neurons; GFP in coelomocytes|Used for measuring signal propagation of \\*unc-31\\* mutant background.|This work|\n|AML546|\\*wtfEx496 \\[pAS3-rig-3P::AI::gur-3G::SL2::tagRFP::unc-54 40ng/ul + pAS3-rig-3P::AI::prdx-2G::SL2::tagBFP::unc-54 40ng/ul]\\*|GUR-3 + PRDX-2, tagBPF and tagRFP expressed in AVA and some pharyngeal neurons (likely I1, I4, M4 and NSM)|Used to activate AVA and observe behavior|This work|", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1862, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1c2fea7a-31f8-4c72-a5cf-52ba0251d57e": {"__data__": {"id_": "1c2fea7a-31f8-4c72-a5cf-52ba0251d57e", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.16, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2a764aac-171b-4d9d-b637-01ef6cf37d3c", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.16, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "92e89060cd3e7eb6f377cdda335829eb5a31742ddb7907db1969db67726dfbd6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Extended Data Fig. 1 | Strains. a, Table of strains used in this work. b, Schematic of CRISPR knockout of *unc-31*.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 115, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5466e323-f610-480a-8e4c-b2fb69d2d2ae": {"__data__": {"id_": "5466e323-f610-480a-8e4c-b2fb69d2d2ae", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.17, para 0](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9ce7f8e9-c6fa-4bfe-9f78-a2fa715355ea", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.17, para 0](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "6ffcdd38e3378f7516c703dbcae84556127982063f356dd86c8e774ba0901ec5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Article", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 9, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "85dfc256-054f-4268-acc5-ecd4ab61ecb7": {"__data__": {"id_": "85dfc256-054f-4268-acc5-ecd4ab61ecb7", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.17, para 11](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c6405b8a-99d0-4a31-94e9-167594821582", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.17, para 11](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "0a6fba33dc727c53f171fdce47cd41574e07a7a15efa3e719d08b506dc7eb5ab", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Extended Data Fig. 2 | Characterization of two-photon optogenetic stimulation and evoked response. a, Two-photon (2p) stimulation spot size (point-spread function). b, Imaging excitation wavelength and intensity were chosen to avoid GUR-3/PRDX-2 activation. GCaMP response to 500 nm activation of GUR-3/PRDX-2 expressing neuron as reported in^24. Vertical grey line indicates light intensity typically used for calcium imaging in present work. Inset: GCaMP6 excitation spectra from^26. Vertical cyan line indicates 505-nm imaging excitation wavelength used in present work. c, d, A neuron near (c) and a neuron far (d) from the objective are photobleached to demonstrate targeted illumination. tagRFP-T is photobleached by 2p stim (20 s illumination, 200 \u00b5W, 500 kHz repetition rate, 3.1 \u00b5m diameter FWHM spot). Difference image shows tagRFP-T fluorescence merged with a false-colour blue-green image to reveal change in intensity after targeted illumination. Only targeted neuron and not nearby neurons appear photobleached. Insets shows zoomed-in image of the targeted neuron's original tagRFP-T intensity (left) and difference image (right). Laser power was chosen to avoid saturated bleaching. For a sense of scale, C. elegans interneuron cell somas are roughly 4 microns in diameter. e, In vivo demonstration of 2p effective spot size. Activity from a neuron expressing GUR-3/PRDX-2 and GCaMP6s is shown in response to a 300-ms 2p stimulation delivered at t=11 s, 4 \u00b5m beyond the \u2248 3.5 \u00b5m diameter soma on the optical axis (z), and at t = 35 s, centred on the soma (t = 35 s). Only on-target soma stimulation evokes a transient, called an \u201cautoresponse\u201d. A stimulus artefact at t = 35 s is visible because no smoothing or filtering is applied to this trace. Schematic via BioRender. f, Distribution of autoresponses under typical stimulus conditions (1.2 mW, 500 kHz; 0.5 s for WT, 0.3 s for unc-31). Autoresponses are required for inclusion. g, Measured calcium response of neuron AIY to optogenetic stimulation of AFD. Compare to figure 4b in ref. 48. A variety of stimulus durations was used to generate autoresponses of different amplitudes (n = 1 (0.1 s), n = 2 (0.15 s), n = 1 (0.2 s), n = 3 (0.25 s), n = 3 (0.3 s), n = 3 (0.35 s), n = 6 (0.4 s), n = 2 (0.45 s), n = 4 (0.5 s) cross-hairs indicate s.d. h, Blue light evoked more reversals in animals expressing GUR-3/PRDX-2 in AVA (n = 11 animals) than WT (n = 8 animals). \\~480 nm peaked light was delivered to freely moving animals. Unpaired t-test, p = 0.025. Bars show mean and s.d. i, j, Probability density (i) and CDF (j) of evoked calcium responses in a 30-s post-stimulus window for the targeted neuron (0 \u00b5m) or for neurons different distances away. Autoresponses are required. Cross-hairs in j, 75% cumulative distribution at \u0394F/F0 = 0.1.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2811, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d1c80208-10fd-4bd8-bf8b-40cbdcf9c647": {"__data__": {"id_": "d1c80208-10fd-4bd8-bf8b-40cbdcf9c647", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.18, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "00c6f0bd-fca0-44a6-832d-b94199221cc1", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.18, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "9c40f935fe77040adc2e8951a82450f88dd57e0ce00cb621d542f58f14cbb838", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Extended Data Fig. 3 | Signal propagation map.** a, Mean amplitude of neural activity in a post-stimulus time window (\\langle \\Delta F / F\\_0 \\rangle\\_t) averaged across trials and individuals for WT background. White indicates no measurement. (n = 113 animals) For a measurement to be included, a stimulus event is required to evoke a response in the stimulated neuron. Same measurements as in Fig. 2a, but here all neurons that respond are shown, even if they are never stimulated. b, Number of stimulation events (orange) and number of datasets (animals) in which the neuron was observed (blue) for each neuron is shown.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 625, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9a6971fe-9f1e-4b47-9862-36dc80b1b686": {"__data__": {"id_": "9a6971fe-9f1e-4b47-9862-36dc80b1b686", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.19, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8d5c48ca-df50-4bdb-84c5-c34b99e2cdea", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.19, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "791cfdfc8dc240ffe97b3da520388214c3305121b589f8a317c232e50aa0ab90", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Extended Data Fig. 4", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 22, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1693ff73-9dc4-40d0-b780-00b92cf6e0d8": {"__data__": {"id_": "1693ff73-9dc4-40d0-b780-00b92cf6e0d8", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.19, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "18f5f98e-51da-4d50-9709-c18f77f5be4f", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.19, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "a0a7f18c9f84e9548841faeb8c10005047cc5649ae5731de4a9e2eb2a9d7ef94", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Observations and false discovery rate of neuron pairs", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 55, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "40968231-3e3b-4550-bb82-3bfd5ddb9a1a": {"__data__": {"id_": "40968231-3e3b-4550-bb82-3bfd5ddb9a1a", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.19, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0892f99b-ac89-47ed-bac0-1986b05b5315", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.19, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "a39a9b470b75ab89bdc62c19f5e84b3334db6f1f48ed5898c75e729910ae92fd", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "in the signal propagation map.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 30, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f60f802d-836f-447a-ac25-86d8f5bc4a86": {"__data__": {"id_": "f60f802d-836f-447a-ac25-86d8f5bc4a86", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.19, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "67ec8127-cd89-4e6b-b098-e19043e3ab84", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.19, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "7e6d1fbf8915c2b21075fa6eab1524899d1784f99e24dcd66f6d4e974468035a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "| a      | Number of Observations | b                                        | q-Values |\n| ------ | ---------------------- | ---------------------------------------- | -------- |\n| -0.6   | 50                     | -0.5                                     | 2        |\n| 402020 | -0.4                   | 30                                       | -0.3     |\n| 20     | -0.2                   | 10                                       | 0.1      |\n| 0.0    | stimulated             | stimulated                               |          |\n| 201.0  | 3711120                | 201.0                                    | 2459820  |\n| 20     | 0.5                    | 18556                                    | D        |\n| 0.5    | 12299                  | 0.0                                      | 0        |\n| 0      | 30                     | 60                                       | 0.00.00  |\n| 0.25   | 0.50                   | Minimum number of observations of a pair | q        |", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 989, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "66bbb7c2-2cf1-4b2b-ba11-c426cd6bee3e": {"__data__": {"id_": "66bbb7c2-2cf1-4b2b-ba11-c426cd6bee3e", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.19, para 12](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "af00cf08-3ffa-43eb-8115-e3e6a257a450", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.19, para 12](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "c3e7b96a256bddc00b5ee0fdf381a700555db53985d29bd9656fdc20025005db", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "They provide a metric of significance for assessing whether a neuron pair is functionally connected based on the number of observations and the magnitude of the response transients, taking into consideration the number of multiple hypotheses tested. Cumulative distribution is also shown (bottom).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 297, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "61fbed59-db10-4f6f-b314-f9ee8ff7a7a4": {"__data__": {"id_": "61fbed59-db10-4f6f-b314-f9ee8ff7a7a4", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.19, para 14](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "94482ae9-8846-4fc8-a344-0c3d1395981f", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.19, para 14](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "69313e77cbca2a9e185a9f82a09d1271e324b3ab13337fafbc6fd4c66cd4f616", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "ASGR often exhibits activity immediately following stimulation of AVJR, but because its q value is greater than 0.05, it does not meet the stringent statistical threshold to be deemed \u201cfunctionally connected\u201d. Top: mean (blue) and s.d. (shading) across trials and animals.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 272, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f63e197c-f58d-4214-88e4-068b831ef3e6": {"__data__": {"id_": "f63e197c-f58d-4214-88e4-068b831ef3e6", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.20, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f364759e-8960-472b-8a7b-dbe0abc1b0c9", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.20, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "e5524047f1bcda59c084c46b62b5ceebf468da053725ad0026e53030a87d8b11", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "0.4\n-0.3\n-0.2\n-0.1\n0.0\n-0.1\n-0.2\n-0.3\n<-0.4\n0.5 0.0\nq value\nNo\nmeasurement\nNot\nDisplayed", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 88, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d0863798-6b8f-4c70-8abe-f9fddfbd036b": {"__data__": {"id_": "d0863798-6b8f-4c70-8abe-f9fddfbd036b", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.20, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f31176b0-4aa6-4037-b516-11b1b69875b7", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.20, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "a7bdcf6097ca5f82e6c23306fd15fbd34a01db2e3706b15c062c312e1ea024d0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "b\nresponding\nstimulated\n-0.35\n0.30\n0.25\n0.20\n0.15\nNo\nmeasurement\nNot\nDisplayed\n0.10\n0.05\n0.00\nqeq-Values", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 104, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "76d6dd64-7560-4157-8b58-16184ad534f3": {"__data__": {"id_": "76d6dd64-7560-4157-8b58-16184ad534f3", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.20, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c3460bc5-c4a9-4679-8d5b-19583148279a", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.20, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "ac9a96864de3488977f042f0b5cef624a74b379f3abb73c341219c8aba7ee262", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Extended Data Fig. 5 | Signal propagation map showing false discovery rates for functional connections and non-connections. a, Map of functional connections showing downstream calcium response amplitude and false discovery rate for WT. Same as Fig. 2 except here neurons that are observed but not stimulated are also included. Note the colour bar has two axes. Mean amplitude of neural activity in a post-stimulus time window (\\langle \\Delta F / F\\_0 \\rangle\\_t) averaged across trials and individuals is shown. q value reports false discovery rate (more grey is less significant). White indicates no measurement. Autoresponse is required for inclusion and not displayed (black diagonal). (n=113 animals). b, Map of functionally not connected pairs. The false discovery rate, q\\_eq, is reported for declaring a neuron pair to be not functionally connected. Lower q\\_eq (more red) indicates higher confidence that the observed downstream calcium activity is equivalent within a bound \\epsilon to a null distribution of spontaneous activity. The false discovery rate takes into consideration the amplitude of the calcium transient, the number of observations and the number of hypotheses tested.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1193, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "37a4810d-9c32-43de-8ae6-2844c40e910b": {"__data__": {"id_": "37a4810d-9c32-43de-8ae6-2844c40e910b", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.21, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f4a9e4da-ece8-4b2c-be36-4bd00607dd00", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.21, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "d5ab5f47105dbda79893df53b9d1efacbe8fdd9e154a6a56714fb8a84ece962b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Responses / Observations", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 26, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7968889b-2591-4618-858a-f90af8a125e7": {"__data__": {"id_": "7968889b-2591-4618-858a-f90af8a125e7", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.21, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7aae6ef2-53d8-41eb-aa2f-70a9ef814716", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.21, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "7a5a33d53378bf3e298f004f7ec6d1fe6e1ec01820af9f6d05bb9d61de0d1240", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# AQR \u2192 FLPR", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 12, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f9f49a07-060d-4a6c-880e-9b40ceb3db10": {"__data__": {"id_": "f9f49a07-060d-4a6c-880e-9b40ceb3db10", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.21, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7df95ad1-5ee3-447d-8928-7717e374f6c7", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.21, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "617951b6a8d57252440b7135c7391f1ffbf3e3f6c51c5accfdee51f5e1065cea", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|      | 1   | AQR (Stim) | Time (s) | FLPR (Resp) |\n| ---- | --- | ---------- | -------- | ----------- |\n| 1.0  | 20\u2080 | -0.8       | 0        | 5           |\n| 20   | 20  | C          | 10       | 20          |\n| -0.6 | 1   | 1          | 0        | 0           |\n| -10  | 10  | 20         | 30       | 10          |\n| 20   | 30  | 0          | -10      |             |", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 370, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e37fd936-aea2-45b1-a5f4-aefba7366acb": {"__data__": {"id_": "e37fd936-aea2-45b1-a5f4-aefba7366acb", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.21, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "10b58cb6-c152-4f46-b5d2-27c8004fb94a", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.21, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "8c2a52dae09709ed4514273e63074ea827fed98c883dc52050ab0e467d44cb06", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Kernel Rise Time", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 18, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "12e6ae31-d025-4b65-bc42-761f17516ff0": {"__data__": {"id_": "12e6ae31-d025-4b65-bc42-761f17516ff0", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.21, para 5](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "37802d52-e794-4a65-b91c-6b9ac620361d", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.21, para 5](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "b30e00145419e7c66cc337742905226dc7059329bb82be3bf77c7b84b15533ec", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Stereotypy of Kernels", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 23, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4d861086-539f-43f7-80a3-a1f09146fa1e": {"__data__": {"id_": "4d861086-539f-43f7-80a3-a1f09146fa1e", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.21, para 6](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0318ac4d-3bfb-42c4-843b-9a797851c0e0", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.21, para 6](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "1940d5637841655af3d55112f863fb2bfdd759e0b08d1a5ea6b8a872e9bd2211", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "| Stimulated | No    |\n| ---------- | ----- |\n| 1.00       | 1     |\n| 0.75       |       |\n| 1.5        | 0.50  |\n| 20         | 20    |\n| 0.25       | 20    |\n| 1.0        | 0.00  |\n| -0.25      |       |\n| 0.5        | -0.50 |\n| -0.75      |       |", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 252, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f668308e-7dd7-4610-9785-e6b6c3333184": {"__data__": {"id_": "f668308e-7dd7-4610-9785-e6b6c3333184", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.21, para 7](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cdcd787e-6737-4366-98cb-68532803cf05", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.21, para 7](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "f787a866c114dc2a829a2d14afbbc743b845804f8eca5b1b7b2ae806f7491ef1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Extended Data Fig. 6", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 22, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cb9ecb95-6a27-448c-8347-488465a963df": {"__data__": {"id_": "cb9ecb95-6a27-448c-8347-488465a963df", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.21, para 8](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ffde91aa-5132-4d64-89c2-f375d9ba1492", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.21, para 8](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "3b4c98e84a1ba4850f7bf7fdcf73591c1a92ea37e5cb988f7b83ab4f7a002156", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Timescales and variability of measured functional connectivity. WT. a, The fraction of stimulation events that evoked a downstream \u201cresponse\u201d is shown for each neuron pair. To be classified as a \u201cresponse\u201d requires a sufficiently large calcium transient amplitude and derivative. Autoresponses are required and not shown (black diagonal).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 338, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4a6567f1-e831-40e8-a707-55f41d59d995": {"__data__": {"id_": "4a6567f1-e831-40e8-a707-55f41d59d995", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.21, para 9](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "83ace67d-40aa-43cf-b2e6-ba8555c5ac30", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.21, para 9](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "ebf9eaf4fd61dc6ebc3a9675d4190ae64b6901b86a78b0100f3892200b125a97", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "b, Kernels are functions that return the downstream neuron\u2019s activity when convolved with the upstream neuron\u2019s activity. Kernels capture properties of the connection independent of variability in the upstream neuron\u2019s autoresponse. c, Kernels are shown for each FLP response to AQR stimulation.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 295, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1c52740d-a105-4dd6-955c-928a0be3ef76": {"__data__": {"id_": "1c52740d-a105-4dd6-955c-928a0be3ef76", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.21, para 10](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "17dd51ae-d5b1-498b-833d-0b74de36e0b7", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.21, para 10](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "7f31ff52d0bdcb6e9adaed67939b2543612e07bb42ede7fd29d99df71b9340db", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "d, Kernel rise time for each measured neuron pair in WT is a metric of signal propagation speed. e, The stereotypy of kernels within each neuron pair is reported by calculating the average correlation coefficient among them. Only neuron pairs with at least two kernels are considered.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 284, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "92a3616d-4b9e-433a-88f6-7b58d0c0f54a": {"__data__": {"id_": "92a3616d-4b9e-433a-88f6-7b58d0c0f54a", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.21, para 11](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "36ddbdcd-d1d1-4abb-951b-e568e47eb074", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.21, para 11](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "6f90ae5d0e07fa3685b22bc987a280ecdea767dbbb47f299308f1fe781655860", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "f, Distribution of the correlation-coefficients of convolved kernels, within each pair of neurons (blue, n = 30,406), and across all kernels measured regardless of neuron pair (orange, n = 113,880,912).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 202, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f7821eae-f5a8-41bf-b2b2-a82af1f1706f": {"__data__": {"id_": "f7821eae-f5a8-41bf-b2b2-a82af1f1706f", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.22, para 6](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "dbb00473-67a6-4f1e-9477-c25e6d5378ae", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.22, para 6](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "8d79f8bc3f9e2698839b8af498683da1013a4476f4f59b5ddd92c9975f5988ad", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Extended Data Fig. 7 | Signal propagation of the *unc-31* background, with defects in dense-core-vesicle-mediated extrasynaptic signalling. a, Same format as Extended Data Fig. 5a. Mean amplitude of neural activity in a post-stimulus time window (\\langle \\Delta F / F\\_0 \\rangle\\_t) averaged across trials and individuals is shown. q value reports false discovery rate and is a metric of significance (more grey is less significant). White indicates no measurement. Autoresponse is required and not displayed (black diagonal). (n = 18 animals). b, *unc-31* mutants had a smaller proportion of measured pairwise neurons that were functionally connected (q < 0.05) than WT (considering only those pairs for which data is present in both WT and *unc-31* mutants). c, Responses to RID stimulation are shown for WT (blue) and *unc-31* (orange). Points are responses, bar is mean across trials and animals. Neurons with the smallest amplitude responses are not shown. Corresponding traces for ADLR, AWBR and URXL are shown in Fig. 4. As in that figure, responses here are shown even for those cases when RID's calcium activity was not measured and therefore do not appear in a. Different inclusion criteria are used here to accommodate cases in which the tagRFP-T expression is dim, as described in the Methods.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1305, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "93f335da-fd72-4f90-939b-16b9b6d3e277": {"__data__": {"id_": "93f335da-fd72-4f90-939b-16b9b6d3e277", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.23, para 0](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "40834f86-6508-48e9-8fec-0eece249960c", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.23, para 0](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "a81acbaf3a32c000e019eb80a182756dfb7667f82b497f1bd059241851464040", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Article", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 9, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f1626a75-8981-40e6-a947-b868dd8486cf": {"__data__": {"id_": "f1626a75-8981-40e6-a947-b868dd8486cf", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.23, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "210d86a4-eede-4fbd-a944-dd46f370eae8", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.23, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "f1664f4d4a1b787338eabf4d1915d3e935a509f33d2282683e7d170b87bcf260", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## a", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d615e1e4-2349-4c60-bb4e-f82e82060258": {"__data__": {"id_": "d615e1e4-2349-4c60-bb4e-f82e82060258", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.23, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f8335d3d-d603-4cc9-becc-70c96809af9b", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.23, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "790c8a61cbceb1625107a4df7b6d076538c3c43f7fbade4a318caea96b156c99", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### WT", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 6, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "bce7e38e-952b-4452-84f2-5d4a30afabcc": {"__data__": {"id_": "bce7e38e-952b-4452-84f2-5d4a30afabcc", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.23, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "71af49f4-ca02-4367-a4cd-2508a1e689f2", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.23, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "8cf0a5ea120f6888df4d0a2f6684a254c39c2aba46b3415a57ad82f72e0d7b71", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "||AWBR (Stim)|AWBL (Resp)|\n|-|-|-|\n|\\*\\*\u0394F/F\u2080\\*\\*|||\n|\\*\\*Sorted Trials\\*\\*|||\n|\\*\\*Time (s)\\*\\*|||", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 99, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "04ddcb8b-47c0-436b-9eb6-d907d04dcc2e": {"__data__": {"id_": "04ddcb8b-47c0-436b-9eb6-d907d04dcc2e", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.23, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5893b89b-1473-4fef-85db-44e904606e19", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.23, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "f648d4851560e45aa77003bb1192195657c08167c82881a09647092bcb8264fb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### unc-31", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 10, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4b4cf9bc-25cf-4a12-af21-e1a888618133": {"__data__": {"id_": 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{"__data__": {"id_": "153b3a40-a911-48ca-b1bf-a28d1de2f7c7", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.23, para 6](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4335299b-e744-47cf-a5a2-161354d0fed4", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.23, para 6](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "47f3e9856b5be384f5504e458b38150648864fb7398c6ccfe5194dc4141dce07", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Extended Data Fig. 8 | Neural responses for some pairs are similar in WT and unc-31-mutant animals. Paired stimulus and response traces of selected neuron pairs with monosynaptic gap junctions (a\u2013c) or monosynaptic chemical synapses (d) are shown in a WT background (left) and in a unc-31-mutant background (right). Top: mean (blue) and s.d. (shading) across trials and animals.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 378, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "96e9ac77-f1b1-41d8-9a19-59360ee77285": {"__data__": {"id_": "96e9ac77-f1b1-41d8-9a19-59360ee77285", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.23, para 7](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0b09f573-0b9c-4fe9-a00d-301057c6ac02", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.23, para 7](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "0c6b21225b7005504f7d45e9bbed6bd8a4485d5a2dc4c8a06f7d0262d8753210", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## b", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, 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"Publication: [Randi2023, p.23, para 18](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "0e7ced077a00d888913f3eb40d7ce2fea7684a110fbfce8c1f8e88614ffc6cd2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|\\*\\*\u0394F/F\u2080\\*\\*|||\n|-|-|-|\n|\\*\\*Sorted Trials\\*\\*|||\n|\\*\\*Time (s)\\*\\*|||", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 72, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "faf3b4e9-6389-4d77-b45f-844f30827747": {"__data__": {"id_": "faf3b4e9-6389-4d77-b45f-844f30827747", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.23, para 19](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1a197462-2a7a-467a-9f2d-e80cdc9876b7", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.23, para 19](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "df432f91afd50d967c851be959bccf4ec0c391d2de5c2cffc9da5d8d73a71a2f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### AVEL (Resp)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 15, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "29acfb60-e1f1-49f1-bc90-855f23fdec23": {"__data__": {"id_": "29acfb60-e1f1-49f1-bc90-855f23fdec23", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.23, para 20](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1b50e8e2-ca15-48f4-84e1-252a47e3a00d", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.23, para 20](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "070bedb0b8bcac8758d3c536710e1b43e46c0318d2ddc0606981ba2863a64b0b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|\\*\\*\u0394F/F\u2080\\*\\*|||\n|-|-|-|\n|\\*\\*Sorted Trials\\*\\*|||\n|\\*\\*Time (s)\\*\\*|||", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 72, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8edda951-7826-44ac-99a4-783cd9fa7278": {"__data__": {"id_": "8edda951-7826-44ac-99a4-783cd9fa7278", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.23, para 21](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "db12350a-1c29-4324-b6b1-223be8c37600", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.23, para 21](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "5c1e404aec6d9866e79839a537b4138548ae963bf9aecd0dc2e2747516615dbe", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### RMDL (Stim)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 15, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8df858e4-b2a8-46be-9a26-b6178c1ad635": {"__data__": {"id_": "8df858e4-b2a8-46be-9a26-b6178c1ad635", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.23, para 22](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7fd37403-b2e2-49f2-8605-25f31eb29d98", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.23, para 22](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "f9c3f83b4d17a2b408bbeb2971d7ed60517e97de71b50fef09c3c2636b657635", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|\\*\\*\u0394F/F\u2080\\*\\*|||\n|-|-|-|\n|\\*\\*Sorted Trials\\*\\*|||\n|\\*\\*Time (s)\\*\\*|||", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 72, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "83240ac8-297d-4524-a1bc-b8d8a61a19c0": {"__data__": {"id_": "83240ac8-297d-4524-a1bc-b8d8a61a19c0", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.23, para 23](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "79e4f04a-c7e0-4cd2-973a-5edd671e90db", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.23, para 23](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "e938a14e0581d6a66e1e7c1485ac8ab90644fd8fc88ac5e4d9a1abacc9f4a17c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### AVEL (Resp)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 15, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "bdbc746b-93cb-443f-bad9-257e9f11a015": {"__data__": {"id_": "bdbc746b-93cb-443f-bad9-257e9f11a015", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.23, para 24](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "025d063f-fdfc-4de8-80a6-12b9314777be", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.23, para 24](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "78b48b962b5b47b10dde8c45b2a869d31e61816de1878f684e0adf8b136d9992", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|\\*\\*\u0394F/F\u2080\\*\\*|||\n|-|-|-|\n|\\*\\*Sorted Trials\\*\\*|||\n|\\*\\*Time (s)\\*\\*|||", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 72, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8fba0c58-24e7-49eb-9b47-fc60ae89ae97": {"__data__": {"id_": "8fba0c58-24e7-49eb-9b47-fc60ae89ae97", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.23, para 25](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d8bcccf4-5c6f-4dab-a4d9-a740083a82f2", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.23, para 25](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "9b1c11bd7c0fc97dcab7f615d5e7b0e19fb503843c2fe140c311012e83eebaf6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## d", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ea12c153-7e64-426f-a851-ec2b7da76264": {"__data__": {"id_": "ea12c153-7e64-426f-a851-ec2b7da76264", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.23, para 26](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "95d1609a-f11f-4ff8-ad1a-ef51a7818bfc", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.23, para 26](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "0b88112cb1f667e22e5bc85e1f10bc58be7cfaca86a39a520f3f62bc514d40e4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### SAAVR (Stim)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 16, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "daff0753-f59a-4d53-8fef-83d58cd24085": {"__data__": {"id_": "daff0753-f59a-4d53-8fef-83d58cd24085", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.23, para 27](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a2e4fd19-fc7c-4c18-86bd-78bb5c5b92ed", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.23, para 27](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "f0d5ce2f4acfbd1a35919078a9383591978c65c1dc673cab3d23fa41836947ee", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|\\*\\*\u0394F/F\u2080\\*\\*|||\n|-|-|-|\n|\\*\\*Sorted Trials\\*\\*|||\n|\\*\\*Time (s)\\*\\*|||", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 72, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f1015683-bf87-4cc4-8902-e8b2ee778f41": {"__data__": {"id_": "f1015683-bf87-4cc4-8902-e8b2ee778f41", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.23, para 28](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "74dd569c-1053-43b2-8b57-3c7792de924b", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.23, para 28](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "1beafa25713aeabf3a86a7d76251096cc9807401a9f272df644aee2d6d3d0911", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### AVAR (Resp)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 15, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "49bd58c7-ac63-42c1-8673-e9c63b410a73": {"__data__": {"id_": "49bd58c7-ac63-42c1-8673-e9c63b410a73", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.23, para 29](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e601b80d-2d07-4262-a052-4bd8605ab29a", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.23, para 29](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "a4004a6642eb3e2fa8657815dc4b13bb077726878f23cea7611112f1c22fd881", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|\\*\\*\u0394F/F\u2080\\*\\*|||\n|-|-|-|\n|\\*\\*Sorted Trials\\*\\*|||\n|\\*\\*Time (s)\\*\\*|||", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 72, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d2d605d6-2315-4af7-b9bb-0827bc316a59": {"__data__": {"id_": "d2d605d6-2315-4af7-b9bb-0827bc316a59", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.23, para 30](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b0575a27-8e3f-4740-b6d9-f611ea3dcab7", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.23, para 30](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "99ddb51d79d54d3ba3086d4b6e46800dc476cdb93faa198b3ca2a2cf69e5ddae", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### SAAVR (Stim)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 16, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "bd4d6a38-214a-4bac-b952-3dbf3b7ee968": {"__data__": {"id_": "bd4d6a38-214a-4bac-b952-3dbf3b7ee968", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.23, para 31](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e984fdbe-a325-4ef1-957f-702acca726fa", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.23, para 31](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "4e2bbb86de06a3bf1d0ed64b8a34a546dc7ebe0f63fb196ab017639c67787359", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|\\*\\*\u0394F/F\u2080\\*\\*|||\n|-|-|-|\n|\\*\\*Sorted Trials\\*\\*|||\n|\\*\\*Time (s)\\*\\*|||", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 72, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "73185a0c-f118-4b5f-85a8-57f46f3e9bcc": {"__data__": {"id_": "73185a0c-f118-4b5f-85a8-57f46f3e9bcc", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.23, para 32](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e45b441e-6af8-44d2-8182-9d07178489bc", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.23, para 32](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "93abd8b95c638c51624e8ae7f0fc73f0ac317a56edb61d404f11c54413f04668", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### AVAR (Resp)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 15, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4b5364ac-f591-48be-b9f5-53ec75fe0b69": {"__data__": {"id_": "4b5364ac-f591-48be-b9f5-53ec75fe0b69", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.23, para 33](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4065d1dc-de05-47dd-8192-0f55162aee67", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.23, para 33](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "56881d671c13b57d58a58a2e740c1407ab6c5faddb1734348e2099a2f9be6387", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|\\*\\*\u0394F/F\u2080\\*\\*|||\n|-|-|-|\n|\\*\\*Sorted Trials\\*\\*|||\n|\\*\\*Time (s)\\*\\*|||", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 72, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5b558c8d-6895-49af-8b5c-bfe2e9a5e27c": {"__data__": {"id_": "5b558c8d-6895-49af-8b5c-bfe2e9a5e27c", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.24, para 0](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "09a03286-c426-4f4a-9a13-b36522c28bd2", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.24, para 0](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "ea35d9acbd46ae131fea66f382e0226cd9d68957de2110a288824a774016879a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Extended Data Fig. 9 | Examples of candidate purely extrasynaptic pairs.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 74, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "795cfd72-d08e-443d-8633-0049453d0fd4": {"__data__": {"id_": "795cfd72-d08e-443d-8633-0049453d0fd4", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.24, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "df2b73b2-7a4c-4536-9d31-e15138d0f72b", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.24, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "bcf413f1d4b221914438368296ff446b69db76e431bf550dc2cad4459eccf16c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "a, Change in activity \\Delta\\langle\\Delta F/F\\rangle versus number of WT observations for our candidate purely extrasynaptic-dependent pairs. Arrows indicate examples shown below. b, List of candidate entirely extrasynaptic-dependent connections. Relevant neuropeptide GPCR expression is listed in Supplementary Table 1,", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 320, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7e224622-2450-4a7b-a7ca-b44b8c19c89c": {"__data__": {"id_": "7e224622-2450-4a7b-a7ca-b44b8c19c89c", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.24, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5ea18b4e-7f3f-4a6f-a4ef-1adb0cefe8a9", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.24, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "f7f9d76884e0b34c22b3333a7533610010e4454e569b280b7b2697b87269ed53", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "compiled from refs. 38,52, following ref. 51. c\u2013e, Paired responses in WT and *unc-31* animals for the candidate extrasynaptic pairs AVER\u2013RMDDR (c), AVDR\u2013ASHR (d) and RMDDR\u2013RMDDL (e), selected among all the candidates as illustrated in a. Top: average (blue) and s.d. (shading) across trials and animals.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 304, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "167ac8a4-9e39-44cf-92f1-50ddde55d316": {"__data__": {"id_": "167ac8a4-9e39-44cf-92f1-50ddde55d316", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.24, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "94b99ee1-7afb-4059-8ccb-6c926a2d10bd", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.24, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "fe2c0dce4f21d742d9f24f2ed58ead4bb38bc0179ff876434cf65df8c94da737", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## a", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1b5bea6d-eff2-421d-9b42-0fbbfcb3594b": {"__data__": {"id_": "1b5bea6d-eff2-421d-9b42-0fbbfcb3594b", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.24, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "de14fbc2-85e3-42b9-9362-6cb43834c47e", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.24, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "2ea695bf5fd42ae27be1d1bf519a2bcf4f7aa58d484ead68c7706ba11604008a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "```html\n|Number of observations|\\Delta\\langle\\Delta F/F\\rangle|\n|-|-|\n|0|0.4|\n|10|0.2|\n|20|0.0|\n|30|-0.2|\n\n```", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 110, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0db352dc-352c-4de7-8807-a0d8a47c6605": {"__data__": {"id_": "0db352dc-352c-4de7-8807-a0d8a47c6605", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.24, para 5](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "19283f7f-c6cb-41c7-a264-71e8d5116000", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.24, para 5](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "34bd99006620e2f611136e89c1dc87a58a4b6dc45be2db8140c794a7221d6147", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## b", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4ac1e28e-2261-498f-bb51-57694f73ea82": {"__data__": {"id_": "4ac1e28e-2261-498f-bb51-57694f73ea82", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.24, para 6](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1a7bae53-7702-4f0e-8ec4-d92cb401fe4c", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.24, para 6](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "7b205102d5c90d5f90065cd198648308bc8f7787b282cb0c9d79245c87ce7585", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* VB1->ADLR\n* RMDDR->AIMR\n* AVDR->ASHR\n* SAAVL->AVAR\n* AVDR->AVDL\n* AWBL->AVDR\n* RIVR->AVDR\n* M3L->AVEL\n* AVDR->AVJL\n* CEPDL->AVJR\n* M3L->AVKL\n* IL2DR->AWBL\n* AVDR->AWBR\n* AWCL->AWBR\n* RMEL->AWBR\n* URXR->AWBR\n* RMDL->CEPDL\n* RMDL->CEPVL\n* AVDR->FLPR\n* M3L->FLPR\n* ASHL->I1L\n* RMDVR->I1L\n* FLPR->I1R\n* M3L->I1R\n* M3L->I2L\n* I3->I2R\n* M3L->I3\n* RIVR->IL1VL\n* M3L->IL2DR\n* M3L->IL2R\n* M3L->M1\n* M3L->M2R\n* IL1DL->M3R\n* I3->OLLR\n* IL1DL->OLLR\n* IL1DL->OLQDR\n* AWBL->RIVR\n* RMDDR->RMDDL\n* AVER->RMDDR\n* RID->RMDDR\n* RMDDL->RMDL\n* AWBL->RMDR\n* RMDVR->RMDR\n* CEPVL->RMDVL\n* IL1DL->RMEL\n* RMDVR->RMEL\n* IL1VL->RMER\n* M3L->RMER\n* AVKL->URBL\n* AVDR->URXL\n* IL1DL->URXL\n* M3L->URYVL\n* AWBR->VB1", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 683, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b9abe3d3-9bd8-45ea-b9aa-c7952081fe2a": {"__data__": {"id_": "b9abe3d3-9bd8-45ea-b9aa-c7952081fe2a", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.24, para 7](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "309bb4a0-5b12-4b7b-aba4-ab5c93c63194", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.24, para 7](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "01faf37c2bc8ea6cc07f9ce46c75fe405c031b791b27e115d801b27ef42dd813", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## c", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0428f9b5-398e-43ed-a00c-5ebf387252e8": {"__data__": {"id_": "0428f9b5-398e-43ed-a00c-5ebf387252e8", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.24, para 8](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1cd98d2e-0205-4fc0-b3c7-812da2481d69", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.24, para 8](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "ab58229d90e680b719bc84160d56f2800124f91ce4d0a08cbd7aa5059a1db709", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### WT", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 6, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1e616d7a-a875-4e67-864a-39c1d088d5be": {"__data__": {"id_": "1e616d7a-a875-4e67-864a-39c1d088d5be", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.24, para 9](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f1a263df-bf60-41a0-b9bd-da02b1d27d8b", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.24, para 9](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "c1b14e1218a058ef8dfa3c025e1ea7a9393bd40e37192e42150c1164cd55f893", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "#### AVER (Stim)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 16, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "118af687-e94a-4d7a-b6f0-cf2e9074454c": {"__data__": {"id_": "118af687-e94a-4d7a-b6f0-cf2e9074454c", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.24, para 10](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e829ee0d-b8da-47c4-834f-1055b4ab78bc", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.24, para 10](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "1bca05937c7cd952b4f3b31a5dd4c2ea07ae9ff84846fe96795e9d42e826dffa", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "```html\n|Time (s)|\\Delta F/F\\_0|\n|-|-|\n|-10|0.0|\n|0|0.0|\n|10|0.5|\n|20|0.5|\n|30|0.5|\n\n```", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 88, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "31c6b3b0-d7ec-4c52-b268-814fd262e18c": {"__data__": {"id_": "31c6b3b0-d7ec-4c52-b268-814fd262e18c", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.24, para 11](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e5408f59-d65c-4d3e-baf1-d8fe237f98af", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.24, para 11](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "5b2414c8735abfdf780d0dad1ce22fbc853c1aa47233559a917f0643ae07b51a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "#### RMDDR (Resp)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 17, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0ebb2034-8d75-458d-b501-46666b57a9c6": {"__data__": {"id_": "0ebb2034-8d75-458d-b501-46666b57a9c6", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.24, para 12](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f9c6a7d3-48a8-4739-acb3-ef209946bcc7", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.24, para 12](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "acecb0b39facfcba32da52b30756575992d30d6ceb4a12612cfade3ed241e29f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "```html\n|Time (s)|\\Delta F/F\\_0|\n|-|-|\n|-10|0.0|\n|0|0.0|\n|10|0.0|\n|20|0.0|\n|30|0.0|\n\n```", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 88, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f3470636-b41a-4e74-ab00-b6d37e15f2fa": {"__data__": {"id_": "f3470636-b41a-4e74-ab00-b6d37e15f2fa", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.24, para 13](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e6454822-f3f1-4a62-be90-674a076f1482", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.24, para 13](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "3aaeab7f63aff95bc49ac4b106066f3b26d72383ef6a7ea7eb6fc58b46e3970b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## d", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0ca36468-fb92-4b52-9460-38d0169f0bd7": {"__data__": {"id_": "0ca36468-fb92-4b52-9460-38d0169f0bd7", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.24, para 14](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4b9aef35-01bb-4f79-9642-1862cfd7aa38", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.24, para 14](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "953e9f0d6c49fa8566590833ca9c594912ed5bc87f81bc687a21f527ee637095", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### WT", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 6, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "aeb7c88d-5fc0-4c73-a7ce-bac5e5686102": {"__data__": {"id_": "aeb7c88d-5fc0-4c73-a7ce-bac5e5686102", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.24, para 15](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d4e5666e-b3e2-4ebf-9936-7746fb95db43", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.24, para 15](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "9cadbfec273e1275751257b21174aeacb55efd23fe0a49eb3e82d974448185f2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "#### AVDR (Stim)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 16, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d889f585-5605-41ef-917e-276a1f074ce6": {"__data__": {"id_": "d889f585-5605-41ef-917e-276a1f074ce6", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.24, para 16](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e32f6ed8-e468-44af-990e-667d11b78423", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.24, para 16](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "167d1dbe6da4b403e0d25b1e546cf26c5aaeb3991c19c052d6f7512b9d9c54c7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "```html\n|Time (s)|\\Delta F/F\\_0|\n|-|-|\n|-10|0.0|\n|0|0.0|\n|10|0.5|\n|20|0.5|\n|30|0.5|\n\n```", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 88, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8c14b7d7-e6cd-4916-958a-5dd84cc0981b": {"__data__": {"id_": "8c14b7d7-e6cd-4916-958a-5dd84cc0981b", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.24, para 17](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "31e8cae2-f22c-401e-966a-0b6dab782a96", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.24, para 17](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "63ac6f9958bf91655bfe9ba228a15fedd7d9f0bbd7f62896334d8357099a4ec4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "#### ASHR (Resp)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 16, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "774bf225-8ebe-49ea-abd3-badc4d4de29a": {"__data__": {"id_": "774bf225-8ebe-49ea-abd3-badc4d4de29a", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.24, para 18](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3625267f-0a1f-496a-a3f0-20e601bcbaff", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.24, para 18](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "a19e9223cb1646e2c75ddc6583a9445dd8dd4faf133862845b687d25cafe598b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "```html\n|Time (s)|\\Delta F/F\\_0|\n|-|-|\n|-10|0.0|\n|0|0.0|\n|10|0.0|\n|20|0.0|\n|30|0.0|\n\n```", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 88, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7cd98073-199a-4a69-b36e-5ad031a3bf86": {"__data__": {"id_": "7cd98073-199a-4a69-b36e-5ad031a3bf86", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.24, para 19](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6227281e-9e42-417e-a1f9-3ef7d8e15760", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.24, para 19](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "b717eed2c79e9042f9deebd521603e3b72fe37dddcaa6215e2218f13869841de", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## e", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d34c3759-50f7-47ff-a336-a3a2ed4050c5": {"__data__": {"id_": "d34c3759-50f7-47ff-a336-a3a2ed4050c5", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.24, para 20](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "36d0e140-7d31-46f3-a451-f03f4f711dcf", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.24, para 20](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "08795fab759d7c671bb2179ddfdef98e6be16cb20bf9c85df3a0b599fa54873c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### WT", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 6, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7dcdabd3-4489-4905-abbc-46b8b1f7629b": {"__data__": {"id_": "7dcdabd3-4489-4905-abbc-46b8b1f7629b", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.24, para 21](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "06203fa0-084f-4618-8110-dbf363fd1aef", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.24, para 21](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "6bf3ae2f9fe3ff0310696772b5049e5e9854cd3b352de5a15d6bbd3cc71cc8e1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "#### RMDDR (Stim)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 17, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f0c7a5df-af7b-444f-bee0-0900a134d4d1": {"__data__": {"id_": "f0c7a5df-af7b-444f-bee0-0900a134d4d1", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.24, para 22](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b9fecbea-8406-49ef-8de2-2c7ef49b487b", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.24, para 22](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "947d013f7a1b7929f93e205fe6d48bfed00018dcfd0a3ed11641ef695b49d25f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "```html\n|Time (s)|\\Delta F/F\\_0|\n|-|-|\n|-10|0.0|\n|0|0.0|\n|10|0.5|\n|20|0.5|\n|30|0.5|\n\n```", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 88, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4c6e8ffb-68f6-4aab-a840-1d4f12bae427": {"__data__": {"id_": "4c6e8ffb-68f6-4aab-a840-1d4f12bae427", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.24, para 23](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bc2111d5-8cc1-4e55-a8d5-27467418ca08", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.24, para 23](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "6e62b56915a5446292611c49e469b303f64aad3f64f10c5ad43f59e96d11fc21", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "#### RMDDL (Resp)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 17, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0d6a1f13-c720-4f92-b4cf-eda9ba7f551f": {"__data__": {"id_": "0d6a1f13-c720-4f92-b4cf-eda9ba7f551f", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.24, para 24](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bf41132e-6246-4b0e-b028-da64c5cbbcac", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.24, para 24](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "aedb310ce2dacad2bf8d5150bd59f9852b3945bc5e4e858560cef67e756e7143", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "```html\n|Time (s)|\\Delta F/F\\_0|\n|-|-|\n|-10|0.0|\n|0|0.0|\n|10|0.0|\n|20|0.0|\n|30|0.0|\n\n```", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 88, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7280175b-70c4-408d-9acc-7bac02f0d8f7": {"__data__": {"id_": "7280175b-70c4-408d-9acc-7bac02f0d8f7", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.25, para 0](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "da55b545-64a4-4a8c-bed7-4e30bc52c8a9", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.25, para 0](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "00f9227831000ce12caec5fe99a34a9ab21077e03fedafd487953120d4fdf4c3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Article", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 9, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "73ad0cee-d2b3-4301-9acf-614d4d639ef2": {"__data__": {"id_": "73ad0cee-d2b3-4301-9acf-614d4d639ef2", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.25, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ee01c6c1-b538-4cde-9c44-16ac507f00c3", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.25, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "3050bbb5ddd85ac01fc3b5339c19db3b54a66fe21c0c3b5bc9bb882e7b7df49c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Extended Data Table 1 | Selected instances of agreement between measured signal propagation and previously reported functional measurements", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 142, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "54658c67-88ec-4051-8688-0bef511f23cd": {"__data__": {"id_": "54658c67-88ec-4051-8688-0bef511f23cd", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.25, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "176d673b-bf9b-43dd-bdd2-d4b31f874d50", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.25, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "4b0aa2dc480f5f3990f2143172704b487666d0d9aefd8e5cb7da6aefaf7b4a96", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Claim|Evidence|Reference|Figure|Finding|Figure|\n|-|-|-|-|-|-|\n|Activation of ASH excites AVA|Paired optogenetic activation (ChR2) and electrophysiology (whole cell patch clamp)|Lindsay et al., 2011 https://doi.org/10.1038/ncomms1304|Fig 4|ASHR->AVAR is functionally connected (qAVDL is functionally connected (q<0.05) and excitatory|Fig 2a; Extended Data Fig 4b|\n|Activation of AFD excites AIY and has a linear response|Paired optogenetic stimulation (ChR2) and electrophysiology (whole cell patch clamp)|Narayan et al., 2011 https://doi.org/10.1073/pnas.1106617108|Fig 4|AFD excites AIY and has a linear response|Extended Data Fig 2g|\n|AVA and AVE can be treated as a single functional unit|AVA and AVE are imaged as a single region of interest during calcium imaging and they yield behaviorally relevant calcium transients;|Kawano et al., 2011 https://doi.org/10.1016/j.neuron.2011.09.005|Fig 1c,d|AVA and AVE have reciprocal functional connections (q<0.05) that are excitatory|Fig 1f; Fig 2a; Extended Data Fig 4b|\n|||Li et al., 2023 https://doi.org/10.3389/fnmol.2023.1228980|Fig 4a; Fig S1|||\n||AVA's and AVE's calcium activity respond similarly to changes in oxygen and have similar tuning to velocity|Kato et al., 2015 https://doi.org/10.1016/j.cell.2015.09.034|Fig S7g-p|||", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1282, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2ceffb49-d3a8-4212-a19e-88e585b9edeb": {"__data__": {"id_": "2ceffb49-d3a8-4212-a19e-88e585b9edeb", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.25, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fd42f624-d61c-418d-a0a1-8a2cde2bc829", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.25, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "522ff14fffbe8c03daad2b6c4ad1ae16fcec3997232a651090bc6d775f979b0c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Comparisons between selected findings from the literature and the current work.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 79, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c5f6b300-6b90-4dbe-aef2-67a2f8b36953": {"__data__": {"id_": "c5f6b300-6b90-4dbe-aef2-67a2f8b36953", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.26, para 0](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0a59444d-eef4-49fc-a8a3-352c128c8b9c", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.26, para 0](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "ea087243b8fc3fa981eb950f9c7e95c2b8230b61d90b7cee0596008e05792efa", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Reporting Summary", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 19, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "469399f4-552e-4152-8383-1cbed3adab4a": {"__data__": {"id_": "469399f4-552e-4152-8383-1cbed3adab4a", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.26, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8d024fd8-019c-474d-a7a7-1aef9ee43ac1", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.26, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "01ef46d5e6f009a2f7541b79ec7add5965d5cc1e2283c5b7e9c7e40bae7ea9bc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Nature Portfolio wishes to improve the reproducibility of the work that we publish. This form provides structure for consistency and transparency in reporting. For further information on Nature Portfolio policies, see our Editorial Policies and the Editorial Policy Checklist.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 276, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "71ede7a4-8aa4-41fb-8a0e-89d31df010c6": {"__data__": {"id_": "71ede7a4-8aa4-41fb-8a0e-89d31df010c6", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.26, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4f92ab72-4933-4505-bec1-d306b030a10a", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.26, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "7eb0fc3336241b30fc2bed3d2ef5816421e60a658f3ebd0a0a3ee47c2174185b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Statistics", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 13, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "43d621a6-47c6-4940-90c4-5de98f35ec0a": {"__data__": {"id_": "43d621a6-47c6-4940-90c4-5de98f35ec0a", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.26, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "dd119945-9e2c-47e3-a039-9638cdc0eaf7", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.26, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "fa87dd57f84d770b25574a0c10e860063b34060a7e6cd47a5773e82168c44177", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "For all statistical analyses, confirm that the following items are present in the figure legend, table legend, main text, or Methods section.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 141, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "67a99581-46ec-475d-9065-a59084b1116f": {"__data__": {"id_": "67a99581-46ec-475d-9065-a59084b1116f", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.26, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "37ae8542-da62-4d03-829e-130f162313db", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.26, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "88a0f4272150df1036bbeb2eaa49f7a0966e97102a5f0739251049c7c4935bdf", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|n/a|Confirmed|\n|-|-|\n||\u2610 The exact sample size (n) for each experimental group/condition, given as a discrete number and unit of measurement|\n||\u2610 A statement on whether measurements were taken from distinct samples or whether the same sample was measured repeatedly|\n||\u2610 The statistical test(s) used AND whether they are one- or two-sided\\Only common tests should be described solely by name; describe more complex techniques in the Methods section.|\n||\u2610 A description of all covariates tested|\n||\u2610 A description of any assumptions or corrections, such as tests of normality and adjustment for multiple comparisons|\n||\u2610 A full description of the statistical parameters including central tendency (e.g. means) or other basic estimates (e.g. regression coefficient)\\AND variation (e.g. standard deviation) or associated estimates of uncertainty (e.g. confidence intervals)|\n||\u2610 For null hypothesis testing, the test statistic (e.g. F, t, r) with confidence intervals, effect sizes, degrees of freedom and P value noted\\Give P values as exact values whenever suitable.|\n||\u2610 For Bayesian analysis, information on the choice of priors and Markov chain Monte Carlo settings|\n||\u2610 For hierarchical and complex designs, identification of the appropriate level for tests and full reporting of outcomes|\n||\u2610 Estimates of effect sizes (e.g. Cohen's d, Pearson's r), indicating how they were calculated|", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1391, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b828e819-b6aa-4ebe-89f8-cfdab7c1144d": {"__data__": {"id_": "b828e819-b6aa-4ebe-89f8-cfdab7c1144d", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.26, para 5](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "62c47bec-cf6a-48b4-9336-c2ab8ef7d964", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.26, para 5](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "4ea8308ffc172392b142e5014760b32d0de8300434bfe37e6268888b97a06990", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Our web collection on statistics for biologists contains articles on many of the points above.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 94, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "05ca55ca-3edc-4c80-98e3-d0eb5ce0f06b": {"__data__": {"id_": "05ca55ca-3edc-4c80-98e3-d0eb5ce0f06b", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.26, para 6](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b55fa028-c89d-4a91-87f9-890933ee70c4", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.26, para 6](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "352116966272eac54364b418e229e987b037e1f373445ff80e468c87c92d8158", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Software and code", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 20, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7f40d6bb-488d-4493-8042-caba47358f62": {"__data__": {"id_": "7f40d6bb-488d-4493-8042-caba47358f62", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.26, para 8](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "158c0bbe-2e33-4073-beb0-2e24ffa8e8ff", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.26, para 8](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "3ac5f3fb103efeabd3ee7e5da39126062a337346eb594000b90cfe8141891726", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* **Data collection** Software to control acquisition hardware is available at  based\n* **Data analysis** All analysis code is publicly available at  (DOI:10.5281/zenodo.8247256),  (DOI:10.5281/zenodo.8247252),  (DOI:10.5281/zenodo.8247242), and  (DOI:10.5281/zenodo.8247254). Hardware acquisition code is available at  (DOI:10.5281/zenodo.8247258).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 349, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f3b8f897-6ca9-4431-9230-942e0e3afa00": {"__data__": {"id_": "f3b8f897-6ca9-4431-9230-942e0e3afa00", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.26, para 9](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a6bd7873-83bd-4666-afb1-3cf87410ba95", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.26, para 9](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "b1364a07402805175c634829ec90059ec5c67f15cfb89f2277898ebd71318d9e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "For manuscripts utilizing custom algorithms or software that are central to the research but not yet described in published literature, software must be made available to editors and reviewers. We strongly encourage code deposition in a community repository (e.g. GitHub). See the Nature Portfolio guidelines for submitting code & software for further information.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 364, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c3e517de-69db-4ae9-ac18-71a26864e769": {"__data__": {"id_": "c3e517de-69db-4ae9-ac18-71a26864e769", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.27, para 0](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "930eb44e-8523-4190-9f9e-40d9994ccb89", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.27, para 0](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "22d16c4b01e7c610284cab0c911b7e481e638938bf52fd2aea620d397eac2823", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Data", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 6, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "60f6601b-cd73-40e3-b023-fa8b1ad9b2a4": {"__data__": {"id_": "60f6601b-cd73-40e3-b023-fa8b1ad9b2a4", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.27, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5d313834-2340-43f7-a464-c40184d9b0af", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.27, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "b0437458713bfd4e067fbcc903b36c9e29ed6a068a0bbd167f5fec04a6b31076", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "All manuscripts must include a **data availability statement**. This statement should provide the following information, where applicable:", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 138, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "191e9787-80ea-4429-8fe6-9bdc7ed062b6": {"__data__": {"id_": "191e9787-80ea-4429-8fe6-9bdc7ed062b6", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.27, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7f3100b5-0d5a-41d2-a58c-b11a0f224ced", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.27, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "120666c5a0b1c22fb601ea197bbeb65506967bde6790b09728aca17e05576f54", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* Accession codes, unique identifiers, or web links for publicly available datasets\n* A description of any restrictions on data availability\n* For clinical datasets or third party data, please ensure that the statement adheres to our policy", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 240, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0cdc4d21-2a84-488a-83a6-2602ef832d48": {"__data__": {"id_": "0cdc4d21-2a84-488a-83a6-2602ef832d48", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.27, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7ba34ca0-e474-48ef-b159-6086170ad7c6", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.27, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "f87f3c1738c4569022f70af46cb9b9171220fc385aaabed1e103499c5208036e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Machine readable datasets containing the measurements from this work are publicly accessible through on Open Science Foundation repository at", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 141, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "54fe1633-72da-4a8a-a1b1-333e6c18afd9": {"__data__": {"id_": "54fe1633-72da-4a8a-a1b1-333e6c18afd9", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.27, para 5](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5c6d98d6-25e0-46d2-86db-45cc661661a8", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.27, para 5](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "187203509e42facf864897cf7d47927c8984a0be725204905e31d4f61943a899", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ". Interactive browseable versions of this same data are available online at", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 75, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7547a54e-c60a-4b08-926b-a1990db58550": {"__data__": {"id_": "7547a54e-c60a-4b08-926b-a1990db58550", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.27, para 8](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "17fa58f6-7dc1-4d53-9338-5c7d206541b1", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.27, para 8](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "d776d336bf66b218cccfe0d510da61c3d2cc087b27ec1c826f105ce0dde0b5c7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ".", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "98c25c77-ab1c-4824-b6f9-8e8580edc57f": {"__data__": {"id_": "98c25c77-ab1c-4824-b6f9-8e8580edc57f", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.27, para 9](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cf3abbfd-34fb-4157-a087-592811289976", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.27, para 9](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "2e008e3df976cd49ed7dc8897685f30e73bbbfca05d04cc8ed249632ebeee1f9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Human research participants", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 29, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e285f2bd-86aa-41bc-9a18-6260d43e123d": {"__data__": {"id_": "e285f2bd-86aa-41bc-9a18-6260d43e123d", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.27, para 10](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "39a4f245-4405-4783-96c6-075915ba6a13", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.27, para 10](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "c51c2eaba1da616e2eb360d6f8d890d2965e13a4a8d0f676d7b710326a6b8cea", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Policy information about studies involving human research participants and Sex and Gender in Research.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 102, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c581e12f-183f-4156-a700-d126e32db347": {"__data__": {"id_": "c581e12f-183f-4156-a700-d126e32db347", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.27, para 11](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c551f6c6-b822-4bc8-9a7a-cf4737c3f1c3", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.27, para 11](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "88a7d7a2c4b7359b861e9cfcc3ccbb7caee716e2bc52032f94d2c015d355da0c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* Reporting on sex and gender\n  * N/A\n* Population characteristics\n  * N/A\n* Recruitment\n  * N/A\n* Ethics oversight\n  * N/A", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 123, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c962b4bc-7271-4f03-93c0-2fa46dd12157": {"__data__": {"id_": "c962b4bc-7271-4f03-93c0-2fa46dd12157", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.27, para 12](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "dcb49755-aa30-4cc8-a219-7716e00e3b28", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.27, para 12](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "f808dc34cfc3110d2278e4b2d346c46feb78d436df1812ba9c50fbd84ad938ba", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Note that full information on the approval of the study protocol must also be provided in the manuscript.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 105, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "bce9b4c4-f621-42a0-89bb-bcc7dc88f3c6": {"__data__": {"id_": "bce9b4c4-f621-42a0-89bb-bcc7dc88f3c6", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.27, para 13](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bc6abf45-e07e-43d9-ba4a-59c4156541ff", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.27, para 13](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "7eda19405324f4f6a2cbfd195408fa1e412c267126f5a9c94f7089214096b140", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Field-specific reporting", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 26, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b0898f81-6988-4fd3-9eb5-05b35fd08696": {"__data__": {"id_": "b0898f81-6988-4fd3-9eb5-05b35fd08696", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.27, para 14](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "72170550-d326-4432-857b-6b3755ad1e07", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.27, para 14](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "19d10c641bf5cf6cd49301dee3bb3b5550999a048d0a51132ff67ce79c00d42f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Please select the one below that is the best fit for your research. If you are not sure, read the appropriate sections before making your selection.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 148, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "72cc60ad-7297-42ef-8048-36aeb36dccb5": {"__data__": {"id_": "72cc60ad-7297-42ef-8048-36aeb36dccb5", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.27, para 15](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5910deee-d7e3-4d54-98a8-6699249af4d3", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.27, para 15](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "04c15e0952f7c7e3bc56bf6f853ecd5c53eb6f59d717494453c8254ae940af47", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* [x] Life sciences\n* [ ] Behavioural & social sciences\n* [ ] Ecological, evolutionary & environmental sciences", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 111, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7ccf4fe5-b24c-4e53-84fd-5fc450680c60": {"__data__": {"id_": "7ccf4fe5-b24c-4e53-84fd-5fc450680c60", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.27, para 16](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ca554ec9-3e24-4c5a-8961-77e6b15c6683", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.27, para 16](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "8b7aa77a912f95f16fcee0ed847f57f578a35c17fb0c9f4b318265b3d697a4f6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "For a reference copy of the document with all sections, see nature.com/documents/nr-reporting-summary-flat.pdf", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 110, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "36bf89b1-da23-47de-8d35-e6100adbc8de": {"__data__": {"id_": "36bf89b1-da23-47de-8d35-e6100adbc8de", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.27, para 17](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "798b58ed-9300-4820-9206-9d6fb97d4d69", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.27, para 17](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "f6b7642ca212b46bd11596c59b5bab43c2514e82f6ca4d97eac3497f9114c264", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Life sciences study design", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 28, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cb8c5c9b-47bf-48f1-9e9b-fd0afad47793": {"__data__": {"id_": "cb8c5c9b-47bf-48f1-9e9b-fd0afad47793", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.27, para 18](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "855c15f9-10ec-49c1-b336-c5605d4dad25", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.27, para 18](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "8f9b45ba4afbf3f436eb4c5c745b7a5776c246c1eeaafcd22ec18e1a2da24160", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "All studies must disclose on these points even when the disclosure is negative.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 79, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3a57eda5-8aa7-44d0-a02a-f6ac99e8ab7f": {"__data__": {"id_": "3a57eda5-8aa7-44d0-a02a-f6ac99e8ab7f", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.27, para 19](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d2fc122c-08d5-4274-9e0c-1c42354fd511", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.27, para 19](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "8e1cd63b0e8a0550332596114958e3e11c5aeca858cc07910b9f1112bff14f49", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* **Sample size**\n  > No sample-size calculation was performed. We recorded from >113 individual WT-background animals and performed over 20,000 pairwise stimulus response measurements. Sample size was chosen to be many fold larger than typical C. elegans calcium imaging experiments in the field, e.g. Hallinen et al., elife 2021.\n* **Data exclusions**\n  > Inclusion and exclusion criteria are described in the \"Inclusion criteria\" subsection of the Methods, and pasted here:\n  >\n  > Stimulation events were included for further analysis if they evoked a detectable calcium response in the stimulated neuron (autoresponse). A classifier determined whether the response was detected by inspecting whether the amplitude of both the DF/F transient and its second derivative exceeded a pair of thresholds. The same threshold values were applied to every animal, strain, neuron and stimulation event, and were originally set to match human perception of a response above noise. Stimulation events that did not meet both thresholds for a contiguous 4 seconds were excluded. RID responses shown in Fig. 4 and Extended Data Fig. 7c are an exception to this policy. RID is visible based on its CyOFP expression, but its tagRFP-T expression is too dim to consistently extract calcium signals. Therefore in Fig. 4 and Extended Data Fig. 7c (but not in other figures, like Fig. 2) responses to RID stimulation were included even in cases where it was not possible to extract a calcium-activity trace in RID.\n  >\n  > Neuron traces were excluded from analysis if a human was unable to assign an identity or if the imaging time points were absent in a contiguous segment longer than 5% of the response window due to imaging artifacts or tracking errors. A different policy applies to dim neurons of interest that are not automatically detected by the `pseudo''-segmentation algorithm in the 3D image used as reference for the pointset registration algorithm. In those cases, we manually added the position of those neurons to the reference 3D image. If these `added'' neurons are automatically detected in most of the other 3D images, then a calcium activity trace can be successfully produced by the DSMM nonrigid registration algorithm and is treated as any other trace. However, if the `added'' neurons are too dim to be detected also in the other 3D images and the calcium activity trace cannot be formed for more than 50% of the total time points, the activity trace for those neurons is extracted from the neuron's position as determined from the position of neighboring neurons. In the analysis code, we refer to these as `matchless'' traces, because the reference neuron is not matched to any detected neuron in the specific 3D image, but its position is just transformed according to the DSMM nonrigid deformation field. In this way, we are able to recover the calcium activity also of some neurons whose tag-RFP-T expression is otherwise too dim to be reliably detected by the `pseudo''-segmentation algorithm. Responses to RID stimulation shown in Fig. 4 and Extended Data Fig. 7c are an exception to this policy. There, the activity of any neuron for which there is not a trace for more than 50% of the time points is substituted with the corresponding `matchless'' trace, and not just for the manually added neurons. This is important to be able to show responses of neurons like ADL, which have dim tagRFP-T expression. In the RID-specific case, in", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 3448, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "19cab7e7-dd15-4e6a-8661-276a1a266e10": {"__data__": {"id_": "19cab7e7-dd15-4e6a-8661-276a1a266e10", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.28, para 0](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d8041ef3-196c-4952-b3c3-a2c793deadbe", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.28, para 0](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "5184d690198bd9da087807bef0e8db57d79c24de8a74674179ca94fa4f1c104f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "order to exclude responses that become very large solely because of numerical issues in the division by the baseline activity due to the dim tagRFP-T, we additionally introduce a threshold excluding DF/F>2.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 206, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "50dfd93b-3c4f-4249-8f8c-a1e6eadc0699": {"__data__": {"id_": "50dfd93b-3c4f-4249-8f8c-a1e6eadc0699", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.28, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "658a2e18-a998-4912-93ae-f1eb9bbbcc03", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.28, para 1](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "801d37d50610f7fc98278fd097e601791344d2011b7892909f1059550892331e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Kernels were computed only for stimulation-response events for which the automatic classifier detected responses in both the stimulated and downstream neurons. If the downstream neuron did not show a response, we considered the downstream response to be below the noise level and the kernel to be zero.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 302, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "026085e2-e932-407b-956e-0f99ec639aef": {"__data__": {"id_": "026085e2-e932-407b-956e-0f99ec639aef", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.28, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "996ffd90-f6cf-432a-a4f2-4bb523eb39d1", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.28, para 2](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "3fe2fa4259ee2c458484f21686f70a08f8c67ecf00f044d775c676cedbd0ccf0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Replication The number of replications for each WT measurement is presented in Supplementary Figure S5a, and additional related information is presented in Supplementary Figure S6.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 180, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "28e87a84-2dcc-470b-a0b4-9f7d32e8e20c": {"__data__": {"id_": "28e87a84-2dcc-470b-a0b4-9f7d32e8e20c", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.28, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d5fab946-32cd-437c-adf6-a8a8c2405c9b", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.28, para 3](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "f57221fa4e6c38965c8ebbe7b25345e2519fe690000318a1b07c470653a07db5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Randomization Randomization was not relevant to our study because we are not testing an intervention on individuals, but instead mapping out signal propagation in WT and mutant animals.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 185, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3e4ce8c3-dba9-4864-9c13-691c5431f7c4": {"__data__": {"id_": "3e4ce8c3-dba9-4864-9c13-691c5431f7c4", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.28, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ede5a364-9e4c-4e5f-958b-b69e8acedef3", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.28, para 4](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "09af2fdfba27a54cebe26c3c48119e202acf06747025c08c6c2078c537b962ec", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Blinding Humans were blinded to calcium activity when they assigned neurons their identities. An exception is neuron AIY in experiments associated with Supplementary Fig S11. Because AIY's identity is sometimes ambiguous based on its position and color, calcium activity was occasionally used to confirm AIY's identity.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 319, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "81983d32-2675-4a95-aa8b-8347d0503abe": {"__data__": {"id_": "81983d32-2675-4a95-aa8b-8347d0503abe", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.28, para 5](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "51bdee26-6ebd-480b-85eb-690d23b46c87", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.28, para 5](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "38356341137a7fc1634074828495c312c7b582e2a6b37d3539319c779b8b8c39", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Reporting for specific materials, systems and methods", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 55, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "36b50765-cbe3-4dc1-a816-4eabc728ea24": {"__data__": {"id_": "36b50765-cbe3-4dc1-a816-4eabc728ea24", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.28, para 6](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "61ece00a-50f4-4283-ab12-a65b9270f739", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.28, para 6](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "646152d7d5666f260729b69f28c69278e810315b3ae0b16d62dadde818335f8f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We require information from authors about some types of materials, experimental systems and methods used in many studies. Here, indicate whether each material, system or method listed is relevant to your study. If you are not sure if a list item applies to your research, read the appropriate section before selecting a response.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 329, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "96b8fd77-5a78-4143-841c-0d2863773b74": {"__data__": {"id_": "96b8fd77-5a78-4143-841c-0d2863773b74", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.28, para 7](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c97bccc1-5302-4f5d-9dd2-a5356868746f", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.28, para 7](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "2a69d87e0b4323d29be6f61978b219a8b38a9bd03a20ffd6582bc6393cb089eb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Materials & experimental systems", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 35, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3a7bae4f-3e4c-4925-93c0-90f74d59839e": {"__data__": {"id_": "3a7bae4f-3e4c-4925-93c0-90f74d59839e", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.28, para 8](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9655046d-c425-4e23-97b8-5bbcc1030d35", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.28, para 8](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "edae18c27678cd08cc3467209b5b880e75276a5a530116d8dce7e280f9210757", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|n/a|Involved in the study|\n|-|-|\n||Antibodies|\n||Eukaryotic cell lines|\n||Palaeontology and archaeology|\n||Animals and other organisms|\n||Clinical data|\n||Dual use research of concern|", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 185, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "704306a0-4b5a-479c-aafd-5af1d0368e25": {"__data__": {"id_": "704306a0-4b5a-479c-aafd-5af1d0368e25", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.28, para 9](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c925a296-110a-4c05-a649-671c9f263ae0", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.28, para 9](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "ffdc85943ff807dc84cefd2dbfb33965f516c26ed11fa9a18bfcb53a585ccd50", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Methods", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 10, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "910a6b5e-7e6a-42cb-92b9-0e9873d722a7": {"__data__": {"id_": "910a6b5e-7e6a-42cb-92b9-0e9873d722a7", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.28, para 10](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "be3a024d-74c1-47ac-95ec-ec0b4355c027", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.28, para 10](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "9e2bb2a266de21ff7d067cc629a78bf99ac741bb1d2ea32d4e0cc4c86917401e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|n/a|Involved in the study|\n|-|-|\n||ChIP-seq|\n||Flow cytometry|\n||MRI-based neuroimaging|", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 89, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "11be505a-200d-46ca-a270-a072032859cb": {"__data__": {"id_": "11be505a-200d-46ca-a270-a072032859cb", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.28, para 11](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "98bb2e3c-abee-4d6e-9dcd-7d6cec700b7b", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.28, para 11](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "eb436373f40d745bab121dbf590662ffd44a934e1dc36cef6473c1e5e6fd3f32", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Animals and other research organisms", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 38, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "55a9febd-ce47-4518-ae3a-ddff6f2b9570": {"__data__": {"id_": "55a9febd-ce47-4518-ae3a-ddff6f2b9570", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.28, para 12](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0fb97fea-2749-4fc2-8f6f-8b373d56a3a5", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.28, para 12](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "269bd9aab50cebba0a44ad96d931d7c8aaf3736fbcafc7f1d87752a2dadf71b1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Policy information about studies involving animals; ARRIVE guidelines recommended for reporting animal research, and Sex and Gender in Research", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 143, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ed2baa5d-55a0-424f-b433-ba1de7c6ed6e": {"__data__": {"id_": "ed2baa5d-55a0-424f-b433-ba1de7c6ed6e", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.28, para 13](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "db782ac2-f8d0-4ffa-8a7f-42fef8a39711", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.28, para 13](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "b92de03666c2f8b947b7f695d5b9ca0660383ab68d5b623cbbf94f55080d43f8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* **Laboratory animals** C .elegans. Strains used include AML462 and AML508 as described in the \"Strains\" section of the Materials and Methods.\n* **Wild animals** Only laboratory strains were used.\n* **Reporting on sex** Hermaphrodites were studied because >99.8% of naturally occurring C. elegans are hermaphrodites (Corsi, et al., WormBook 2015)\n* **Field-collected samples** N/A\n* **Ethics oversight** No ethical approval or guidance was required because C. elegans are microscopic invertebrate worms.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 504, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "dd986e85-8587-4055-8a0b-e209667d6d56": {"__data__": {"id_": "dd986e85-8587-4055-8a0b-e209667d6d56", "embedding": null, "metadata": {"source document": "Publication: [Randi2023, p.28, para 14](https://www.nature.com/articles/s41586-023-06683-4)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a3fe49c7-5ee5-4d31-92cf-0f7555c5d1a2", "node_type": "4", "metadata": {"source document": "Publication: [Randi2023, p.28, para 14](https://www.nature.com/articles/s41586-023-06683-4)"}, "hash": "ce70ce88c918361d417f5cf0a7eec75c666b3aa6bb9279e6714aac4264e6d0bf", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Note that full information on the approval of the study protocol must also be provided in the manuscript.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 105, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b7823388-958f-4a49-8737-58a509f3c6a9": {"__data__": {"id_": "b7823388-958f-4a49-8737-58a509f3c6a9", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.1, para 1](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c7f6ed77-0cb5-4069-b948-b9c3a91977c1", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.1, para 1](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "91f1c690c27e23d0f9d3b904b58315835d6d8be4ef6f6b06e68daa119d1a77e5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Monoaminergic Orchestration of Motor Programs in a Complex *C. elegans* Behavior", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 82, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a6a7cf0a-a692-4373-b89c-a20b8b8db080": {"__data__": {"id_": "a6a7cf0a-a692-4373-b89c-a20b8b8db080", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.1, para 2](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "df07cccf-8a9d-421a-aa9b-4301ab2316b5", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.1, para 2](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "e8f74d05fa8b28cfa2b4c172eec63ab72e6f41724eb73bb572817aa5cdbec9da", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Jamie L. Donnelly^1, Christopher M. Clark^1, Andrew M. Leifer^2, Jennifer K. Pirri^1, Marian Haburcak^1, Michael M. Francis^1, Aravinthan D. T. Samuel^2, Mark J. Alkema^1\\*", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 172, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6e3d9dd2-bd97-4868-88ca-12e1c714dd76": {"__data__": {"id_": "6e3d9dd2-bd97-4868-88ca-12e1c714dd76", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.1, para 3](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9e83d5f4-8367-4d39-b032-24f9384ad648", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.1, para 3](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "de303006e1de6e1691ea491ffff9486f061ecee4dbdb3204ae6eaa84cbdb1875", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "^1Department of Neurobiology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America, ^2Department of Physics & Center for Brain Science, Harvard University, Cambridge, Massachusetts, United States of America", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 248, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "16864860-4a38-4a49-91b9-3b17c4a67799": {"__data__": {"id_": "16864860-4a38-4a49-91b9-3b17c4a67799", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.1, para 5](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f3e885e7-e968-4237-b30a-20feb7201323", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.1, para 5](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "b6717918a3cd79928391925970a9cbca6cde7e14488dec9c9569cf1d8bc6958e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Monoamines provide chemical codes of behavioral states. However, the neural mechanisms of monoaminergic orchestration of behavior are poorly understood. Touch elicits an escape response in *Caenorhabditis elegans* where the animal moves backward and turns to change its direction of locomotion. We show that the tyramine receptor SER-2 acts through a G\u03b1o pathway to inhibit neurotransmitter release from GABAergic motor neurons that synapse onto ventral body wall muscles. Extrasynaptic activation of SER-2 facilitates ventral body wall muscle contraction, contributing to the tight ventral turn that allows the animal to navigate away from a threatening stimulus. Tyramine temporally coordinates the different phases of the escape response through the synaptic activation of the fast-acting ionotropic receptor, LGC-55, and extrasynaptic activation of the slow-acting metabotropic receptor, SER-2. Our studies show, at the level of single cells, how a sensory input recruits the action of a monoamine to change neural circuit properties and orchestrate a compound motor sequence.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1080, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "263f3e85-77ec-4f7b-a160-50390b13c582": {"__data__": {"id_": "263f3e85-77ec-4f7b-a160-50390b13c582", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.1, para 6](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3fa4d884-151e-4814-a341-414b2ef03e21", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.1, para 6](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "4e5eb0218f82465d13403d78fb0fb9799f241fbc6eb200e7c899f86201e4b10b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Citation:** Donnelly JL, Clark CM, Leifer AM, Pirri JK, Haburcak M, et al. (2013) Monoaminergic Orchestration of Motor Programs in a Complex *C. elegans* Behavior. PLoS Biol 11(4): e1001529. doi:10.1371/journal.pbio.1001529", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 225, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "eda144cf-1c14-4790-9026-8395e4b60b54": {"__data__": {"id_": "eda144cf-1c14-4790-9026-8395e4b60b54", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.1, para 7](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ef0bb1a7-129f-4316-be40-26bb09884a5b", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.1, para 7](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "44bb20cce44aba2bcdf018d3309fe1c886756512168887f849e8f417e4de3344", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Academic Editor:** Andres V. Maricq, University of Utah, United States of America", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 83, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d611497e-6d84-440f-bd5c-5c4e0f96f3d6": {"__data__": {"id_": "d611497e-6d84-440f-bd5c-5c4e0f96f3d6", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.1, para 8](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bc6eff0f-fffd-425b-9776-bc7e2906ac54", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.1, para 8](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "e49acfb6a6b8d30a0b05306e4170fbc8bae092ace74b40ddfcbad17babf36265", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Received** August 1, 2012; **Accepted** February 22, 2013; **Published** April 2, 2013", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 88, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "884d6867-a398-40cc-b490-503bf5f62928": {"__data__": {"id_": "884d6867-a398-40cc-b490-503bf5f62928", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.1, para 9](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5106e69d-e7f4-40d6-867d-0161eb8155ef", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.1, para 9](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "98db87403c6f7322148004b40c64ab5b4d00af9ddd6139b9e5fec495f3597190", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Copyright:** \u00a9 2013 Donnelly et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 273, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "eba83b38-f928-49b9-94a8-dc3d73a22de2": {"__data__": {"id_": "eba83b38-f928-49b9-94a8-dc3d73a22de2", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.1, para 10](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1f7a6922-bcdf-460d-8580-db25540ed0e8", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.1, para 10](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "68779268a1234756bc9077cddbc96475e880ae7d672d563876d2093444779182", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Funding:** This work was supported by the NSF and a Pioneer grant of the National Institutes of Health to ADTS, US NIH grant NS064263 to MMF, and US NIH grant GM084491 to MJA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 303, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e905682e-3b18-4358-bac2-be10a9800e0f": {"__data__": {"id_": "e905682e-3b18-4358-bac2-be10a9800e0f", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.1, para 11](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "efe0db72-4bc8-4e98-9751-9169f3b485a2", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.1, para 11](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "a50c1b38249a0484a35dda8629742a92da3966b19bc67844996a91eb3ab96b87", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Competing Interests:** The authors have declared that no competing interests exist.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 85, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fc804748-6ec7-444e-abb8-5d8267581479": {"__data__": {"id_": "fc804748-6ec7-444e-abb8-5d8267581479", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.1, para 12](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "eb77fcd7-5536-4461-ac20-830a976af85b", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.1, para 12](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "14d5c9d481e78885209e0c429f455577c0a06640b7f16a7f81c29016567fd7f2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Abbreviations:** ACh, acetylcholine; cAMP, cyclic adenosine monophosphate; ChR2, Channelrhodopsin-2; CoLBeRT, Control of Locomotion and Behavior in Real Time; DAG\u03b8, diacylglycerol kinase theta; G\u03b1, G protein-alpha subunit; GABA, gamma-aminobutyric acid; GPCR, G-protein coupled receptor; ICF, intracellular fluid; IPSC, inhibitory post-synaptic current; NGM, nematode growth media; NMJ, neuromuscular junction; NpHR, Halorhodopsin; RGS, regulator of G-protein signaling; t50, time to immobilize 50% of the animals; wt, wild type.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 531, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "21c6737a-81f2-473a-9c8b-e8da8002e009": {"__data__": {"id_": "21c6737a-81f2-473a-9c8b-e8da8002e009", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.1, para 13](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6307b07a-c5d6-476c-8d42-4e58528083de", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.1, para 13](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "028a302cd1b89b18c3fae8736299120e0ef5eb005487915c00c8a90dbd88f36e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* E-mail:", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 9, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c3abea00-60cc-46e6-b5ee-382363bd2fc0": {"__data__": {"id_": "c3abea00-60cc-46e6-b5ee-382363bd2fc0", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.1, para 14](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a1e69c75-cf9b-4e16-bcbc-8317f70c4ff6", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.1, para 14](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "e1c9e9b711f2fa47b35ed8ee8506b946e5a28bc4eaa57df5a4a4c0b2fd144acc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "^1 These authors contributed equally to this work.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 50, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ac51c19e-f553-42f4-9298-eae53d039f15": {"__data__": {"id_": "ac51c19e-f553-42f4-9298-eae53d039f15", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.1, para 15](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3b202c59-fdc4-4274-936d-22e10a08d0e5", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.1, para 15](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "2e2582eabb0e01fe12843a555e6d80e38131443fac9f7b0f05f7ea79f7321e8d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "^2 Current address: Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 126, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4b9b4966-4f9d-4c77-bd8c-da5bd851dc9b": {"__data__": {"id_": "4b9b4966-4f9d-4c77-bd8c-da5bd851dc9b", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.1, para 16](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b215b7f5-6c16-4a3d-8670-a0be63be4ac9", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.1, para 16](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "dd7cd136f99633b26f5dcfce6aeb218120cf8cc10bbf4dbeb911b6d33d3d9bbc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Introduction", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 15, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e58ec2d0-1f81-44ee-a3db-a25a366d9f22": {"__data__": {"id_": "e58ec2d0-1f81-44ee-a3db-a25a366d9f22", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.1, para 17](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6d0d36ff-6a15-4323-b620-ca1aea137215", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.1, para 17](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "f1b9b2b9b76645600d6d660df153577744c6e59248660637174c3c2940212996", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Complex behaviors require the temporal coordination of independent motor programs in which neurotransmitters and neuromodulators orchestrate the output of neural circuits. How the nervous system directs sequential activation and inhibition of assemblies of neurons, however, is largely unclear. Neurotransmitters can directly activate ligand-gated ion channels at synapses, inducing rapid changes in the electrical activity of postsynaptic cells. Neuromodulators generally act through G-protein coupled receptors (GPCR) that activate intracellular signaling cascades with slower but longer lasting effects. The release of neuromodulators can activate or refine basic motor patterns generated by fast-acting neurotransmitters in a neural network \\[1\u20133].", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 752, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5610c632-d1d4-48b4-a8ce-9b0e61226061": {"__data__": {"id_": "5610c632-d1d4-48b4-a8ce-9b0e61226061", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.1, para 18](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cad50bde-b2c4-4f0c-8c74-739a9d60b026", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.1, para 18](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "e075c49b39407f06a34a8b85230dd6380d02060989ed09207588f2a6a8f78a8e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "In mammals, monoamines such as serotonin, dopamine, and noradrenaline are associated with specific behavioral states. Adrenergic modulation provides one of the most striking examples of the coordination of behavior and physiology to reflect an internal state of stress. Adrenergic transmitters stimulate the amygdala and increase heart rate, muscle tone, oxygen supply to the brain, and the release of glucose from energy stores to prepare for a fight-or-flight response \\[4]. Noradrenaline and adrenaline are not used by invertebrates, but the structurally related monoamines octopamine and tyramine are often considered as the invertebrate counterparts of these adrenergic transmitters \\[5]. Octopamine and tyramine have been implicated in subordinate behavior in lobsters \\[6], the honey bee sting response \\[7], the energy metabolism of flight in locusts \\[8], aggression in crickets and fruit flies \\[9\u201312], and the escape response of *C. elegans* \\[13]. Pioneering studies in the locust \\[14], mollusks \\[15], and crustaceans \\[16] have supported an \u201corchestration hypothesis\u201d \\[17] where monoamines control behavioral states through the recruitment of distinct neural circuits. However, the sensory input that triggers the release of monoamines and the molecular and neural coding of these behaviors remain poorly understood.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1332, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c1f22d88-fd3b-469e-9a59-2cda9ade3bc5": {"__data__": {"id_": "c1f22d88-fd3b-469e-9a59-2cda9ade3bc5", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.1, para 19](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b56cf285-6a59-4408-a3c4-cb6a70fed2b1", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.1, para 19](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "f2e7b12d48627c61dc5d5268a6a4a0752064d590ee02a4bca6687d3294eb538e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The *C. elegans* escape response consists of a behavioral sequence used by the animal to navigate away from a threatening stimulus. *C. elegans* moves on its side by propagating a sinusoidal wave of ventral-dorsal muscle contractions along the length of its body \\[18]. Locomotion is normally accompanied by exploratory head movements in which the tip of the nose moves rapidly from side to side. Gentle touch to the head elicits a backing response and the suppression of exploratory head movements \\[13,19]. The backing", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 520, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8350cb47-2e11-4b48-9db4-0a8fb198c980": {"__data__": {"id_": "8350cb47-2e11-4b48-9db4-0a8fb198c980", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.2, para 0](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8bbe6531-d7c2-463c-b292-f684839c23b0", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.2, para 0](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "f3cc502702b8f0484e04cd5e3b9ff7834545a03a44a9d967a0e0296d4cb0a886", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Monoaminergic Orchestration of a Complex Behavior", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 51, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4c0d699a-9ec2-4293-bb75-082b0d832cc5": {"__data__": {"id_": "4c0d699a-9ec2-4293-bb75-082b0d832cc5", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.2, para 1](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "44a3f0ae-18b9-4f95-bbd2-22dac70edf3b", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.2, para 1](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "228f360ba5be6e87b85bc66d45dec44775fd0b6949d0e3420b88311308a748ac", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Author Summary", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 17, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b01c3748-098b-4e94-ba6e-0b618a1997ce": {"__data__": {"id_": "b01c3748-098b-4e94-ba6e-0b618a1997ce", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.2, para 2](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0cb9024a-40c9-4cb5-81b8-c6a396ea610c", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.2, para 2](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "019538097d1d4033f835bb69c3ceb2dfebac83c54e84d9d4160d097f98938036", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "How the nervous system controls complex behaviors has intrigued neurobiologists for decades. There are many examples where sequential motor patterns of specific behaviors have been described in great detail. However, the neural mechanisms that orchestrate a full behavioral sequence are poorly understood. Gentle touch to the head of the roundworm *C. elegans* elicits an escape response in which the animal quickly moves backward. The reversal is followed by a deep turn that allows the animal to change its direction of locomotion and move away from the threatening stimulus. We found that the neurotransmitter tyramine controls the initial reversal phase of the escape response through the activation of a fast-acting ion channel and the later turning phase through the activation of a slow-acting G-protein coupled receptor (GPCR). We show that this tyramine GPCR is expressed in neurons that make contacts with the ventral muscles of the animal. Activation of this receptor facilitates the contraction of ventral muscles and thus allows the animal to turn and resume locomotion in the opposite direction during its escape. Our studies show how a single neurotransmitter coordinates sequential phases of a complex behavior through the activation of distinct classes of receptors.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1283, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ae5aa460-5459-4eec-a2d8-8b0621a76130": {"__data__": {"id_": "ae5aa460-5459-4eec-a2d8-8b0621a76130", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.2, para 3](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "927bef0a-0f6e-449e-be8b-093b501e57c2", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.2, para 3](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "406d88c9b1fcc0971eb0def123a1bb50565ea43331fe3739c01253c586efead9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "response is usually followed by a deep ventral head bend, allowing the animal to make a sharp (omega) turn and change its direction of locomotion. The completion of the entire escape response takes approximately 10 s and requires sensory processing, decision-making, and sequential inhibition and activation of distinct motor programs. Therefore, the anterior touch response is a highly orchestrated motor sequence with complexity far beyond that of a simple reflex.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 466, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b0a05f3d-0ad8-46cc-b16d-01d0b1f54361": {"__data__": {"id_": "b0a05f3d-0ad8-46cc-b16d-01d0b1f54361", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.2, para 4](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e5b734b5-33c2-4efd-a214-49b51638c2fb", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.2, para 4](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "ea82d396ec16b2ff085a1f2a0725e698837c38aa043845a778e40080ef667ff8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The neural wiring diagram in combination with genetic and laser ablation experiments has provided a framework for the neural circuit that controls the initial phase of the escape response \\[19\u201321]. *C. elegans* has a single pair of tyraminergic motor neurons that are essential in coordinating the backing response with suppression of head movements \\[13]. Synaptic activation of the tyramine-gated chloride channel, LGC-55, inhibits forward locomotion and induces the relaxation of neck muscle \\[22]. The coordination of these motor programs increases the animals' chances of escaping from predacious fungi that use constricting rings to catch nematodes, illustrating the vital importance of monoaminergic motor control \\[23,24]. How this initial phase of the escape response is temporally linked to later stages in which the animal makes a sharp turn to navigate away from the stimulus is unknown. To elucidate how monoamines may orchestrate the activity of specific neural circuits in complex behaviors, we analyzed the role of tyramine in *C. elegans* locomotion during the escape response. We show that the extrasynaptic activation of a G-protein coupled tyramine receptor generates asymmetry in a locomotion program, thus allowing the animal to execute a deep ventral turn and navigate away from the stimulus.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1315, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5d5c3c5c-9a28-46cf-8f9d-ae51d8fb5c20": {"__data__": {"id_": "5d5c3c5c-9a28-46cf-8f9d-ae51d8fb5c20", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.2, para 5](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8eb3cb07-2eb4-43d4-a62e-5fb219b947f0", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.2, para 5](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "25972f740645bfebe6f288e9726913e4b5cf01cd16772a5c2e1ad86bd765af0f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Results", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 10, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e6161cd6-aed3-486d-844e-5c3f2b107293": {"__data__": {"id_": "e6161cd6-aed3-486d-844e-5c3f2b107293", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.2, para 6](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e234d08b-053b-4092-90be-2df07484f5e6", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.2, para 6](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "1281f119d4da32539bd8fd9e8d86bf5dcae58207236d36bc5545581944eaee57", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### ser-2 Mutants Are Resistant to Exogenous Tyramine", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 53, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "801da36d-38e5-4804-ba68-eb10be66b996": {"__data__": {"id_": "801da36d-38e5-4804-ba68-eb10be66b996", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.2, para 7](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b147a329-57ba-407d-8bb7-81c3abb8e7f0", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.2, para 7](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "8b76885e8c9a267a96fd38c147e0ac145820fe5829501f4e00edc048ec5d403d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "*C. elegans* become immobilized on plates containing exogenous tyramine in a dose-dependent manner (Figure 1A and Figure S1) \\[22]. Three GPCRs have been shown to bind tyramine with high affinity: TYRA-2, TYRA-3, and SER-2 \\[25\u201328]. To determine whether the effects of tyramine are mediated by these GPCRs, we examined the locomotion of *ser-2(pk1357* and *ok2103)*, *tyra-2(tm1815)*, and *tyra-3(ok325)* deletion mutants on agar plates containing exogenous tyramine. Wild-type, *tyra-2*, and *tyra-3* mutant animals become immobilized on 30 mM tyramine within 5 min (Figure S2). However, *ser-2* mutant animals sustained movement on plates containing exogenous tyramine (Figure 1A\u2013C and Figure S1). Sensitivity to exogenous tyramine is restored back to wild-type levels in *ser-2* mutants containing a *ser-2* genomic transgene (Figure 1B,C and Figure S2). This indicates that exogenous tyramine mediates its paralytic effects through the hyperactivation of endogenous tyramine signaling pathways that are at least in part dependent on SER-2.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1043, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b3a26349-60b3-4d3e-8958-f5e78f93b351": {"__data__": {"id_": "b3a26349-60b3-4d3e-8958-f5e78f93b351", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.2, para 8](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7cb5e1c2-04f1-4724-864b-7f2723915bc8", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.2, para 8](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "9d5b648c36a4f1fe5258dc13731528391804f130ed9c3691cc272bb903989236", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We have previously shown that activation of the tyramine-gated chloride channel, LGC-55, inhibits head movements and forward locomotion \\[22]. Exogenous tyramine initially induced backward locomotion and the inhibition of head movements in both the wild-type and *ser-2* mutants. However, unlike the wild type, *ser-2* mutants recovered and resumed forward locomotion and head movements within minutes. Body movements of *lgc-55* mutants are inhibited, similar to the wild-type, but head movements are sustained on exogenous tyramine (Figure 1C,D). *lgc-55; ser-2* double mutants largely persisted both head and body movements on exogenous tyramine, however locomotion remained slightly uncoordinated. This indicates that while the activation of the ionotropic LGC-55 and metabotropic SER-2 receptor are required for paralysis, exogenous tyramine may affect locomotion through the activation of other receptors.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 911, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "685e9c99-d4be-4e71-bb78-a97b33a922af": {"__data__": {"id_": "685e9c99-d4be-4e71-bb78-a97b33a922af", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.2, para 9](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7a06f01f-dbfe-46e5-b29d-0e6857b7c341", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.2, para 9](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "72b6057d52642fc58ebc2a9e2928f9fe96dcadcfaf3c88930ebd54ad77572ad0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Head movements and body movements are controlled by distinct groups of muscles and motor neurons \\[13,20]. In wild-type animals the inhibition of head movements occurred rapidly (half time to immobilization, ti50 = 77 \u00b1 2 s) and was followed by the slower inhibition of body movement (ti50 = 149 \u00b1 3 s). This suggests that signaling pathways with distinct kinetics contribute to tyramine\u2019s effects. The sustained body movements of *ser-2* mutants on exogenous tyramine make it difficult to dissect the effects of exogenous tyramine on head movements. Therefore, we analyzed the effect of tyramine on head movements in an *unc-3(e151)* mutant background. *unc-3* mutants display few body movements, but have normal head movements \\[29]. Head movements of *ser-2 unc-3* double mutants were inhibited on exogenous tyramine, like those in the wild-type and *unc-3* mutants (Figure 1D). Consistent with our previous observation \\[22], head movements were sustained in *lgc-55; unc-3* double mutants. The kinetics and distinct inhibition of head and body movements of *lgc-55* and *ser-2* mutants indicates that exogenous tyramine induces the fast immobilization of head movements mainly through the hyperactivation of the ionotropic tyramine receptor LGC-55 followed by the immobilization of body movements through hyperactivation of the metabotropic tyramine receptor SER-2.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1370, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cfb8c4ec-82a0-4efe-aa16-b17affc7452e": {"__data__": {"id_": "cfb8c4ec-82a0-4efe-aa16-b17affc7452e", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.2, para 10](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0b7517b9-9c6e-4970-8400-04a2080e1083", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.2, para 10](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "7eeb5b2fae5be3afd183d7a0c801a893957eca07ae0f91025d4cabd8bf1b0ff4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### G\u03b1o Signaling Pathway Mutants Are Resistant to Exogenous Tyramine", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 69, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a73bf79b-d741-438e-94e0-ab58a11b219a": {"__data__": {"id_": "a73bf79b-d741-438e-94e0-ab58a11b219a", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.2, para 11](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1c32a1c4-257c-442b-a271-380bf50d96ad", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.2, para 11](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "298b38e319a306f5a53fbf2546a94709c23d54376065d1fa02bb189391b15166", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "To identify genes involved in tyramine signaling, we performed a genetic screen for mutants that are resistant to the immobilizing effects of exogenous tyramine on body movements. Four isolates from this screen, *zf47*, *zf97*, *zf98*, and *zf133*, sustained movement on plates containing 30 mM tyramine. Genetic mapping, complementation tests, and sequence analysis showed that *zf47* was an allele of *goa-1*. *goa-1* encodes the *C. elegans* ortholog of the neural G protein-alpha subunit of the G\u03b1o class. GOA-1/G\u03b1o is expressed throughout the nervous system and is thought to negatively regulate synaptic transmission through the inhibition of EGL-30, the *C. elegans* G\u03b1q ortholog \\[30\u201332]. We found that *zf97*, *zf98*, and *zf133* were alleles of *dgk-1*, which encodes the *C. elegans* ortholog of the vertebrate brain diacylglycerol kinase theta (DAG\u03b8) \\[32,33].", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 872, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c6f7eeae-b9bc-45c5-ae64-d4ae8ff7bd5d": {"__data__": {"id_": "c6f7eeae-b9bc-45c5-ae64-d4ae8ff7bd5d", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.3, para 0](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0447babe-87ba-4569-8f8d-0ba21c4d1b77", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.3, para 0](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "c8cc47e02b3224d9997000bff40e77b5210c74535e9839794440007cdf4d6dea", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Figure 1. ser-2 mutants are partially resistant to the paralytic effects of exogenous tyramine.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 97, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c3d2c4fb-8e2a-42b7-b2d0-a1024bc550b6": {"__data__": {"id_": "c3d2c4fb-8e2a-42b7-b2d0-a1024bc550b6", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.3, para 1](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c9db7a8b-21f9-4f11-9ba4-fb1ef95da220", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.3, para 1](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "781ea57756f889cc5df747ba203ef2c1c05d09005d17813d51365a419816b161", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "(A) Tyramine induces immobilization in a dose-dependent manner. Shown is the percentage of animals immobilized after 10 min on agar plates supplemented with tyramine. Wild-type animals become fully immobilized at concentrations above 30 mM tyramine, while ser-2 mutants continue sustained movement. Each data point represents the mean \u00b1 the standard error of the mean (SEM) for at least three trials, totaling a minimum of 30 animals.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 434, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f4629d8f-8de3-485e-8429-6218d1ebd6cc": {"__data__": {"id_": "f4629d8f-8de3-485e-8429-6218d1ebd6cc", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.3, para 2](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "461b5424-0905-43d4-a953-786a42ef56f6", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.3, para 2](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "09d9deda7938b12f44316ad976944c45ac7e129e0820179be4149377b7fb46dc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "(B) G-protein signaling mutants are resistant to the paralytic effects of exogenous tyramine. Shown is the percentage of animals that become immobilized after 10 min on 30 mM tyramine. Each bar represents the mean \u00b1 SEM for at least four trials totaling a minimum of 40 animals. (Inset) Schematic representation of the G\u03b1o and G\u03b1q signaling pathways that modulate locomotion in *C. elegans*. The genetic data suggest that SER-2 acts in the G\u03b1o pathway. The names of the human orthologs are shown. Rescue denotes the transgenic line Pser-2::SER-2; ser-2(pk1357).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 561, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "68c2c364-5b54-4a88-869a-fd5ad67ecfb0": {"__data__": {"id_": "68c2c364-5b54-4a88-869a-fd5ad67ecfb0", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.3, para 3](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "296084f1-9927-4edb-a580-4c7135ab4822", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.3, para 3](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "010449cb5f911f4a2ee674fd400152d91c938dd209466d64d9ba1f1c57f4fc08", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "(C, D) Tyramine affects locomotion and head movements through different mechanisms. Shown is the percentage of animals with sustained body (C) or head (D) movements on 30 mM tyramine. ser-2 mutants are partially resistant to the effects of tyramine on body movements, but not head movements. lgc-55 mutants continue to move their heads through the duration of the assay. Each data point represents the mean percentage of animals that become immobilized by tyramine each minute for 20 min \u00b1 SEM for at least six trials, totaling a minimum of 60 animals. Head movements were analyzed in an unc-3 mutant background. unc-3 mutants make few body movements but display normal head movements, and are wild-type for the ser-2 and lgc-55 loci. Statistical significance to wild-type: \\*\\*\\*p<0.0001, two-tailed Student's *t* test. See also Figures S1 and S2.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 848, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e154da42-60d3-4dda-89ec-bcb188f2427e": {"__data__": {"id_": "e154da42-60d3-4dda-89ec-bcb188f2427e", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.3, para 5](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9e014564-f780-4475-a74d-abc5be7074ca", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.3, para 5](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "345e482436feabd71de39cdc5bccadc6d4ae3ef4cf6f5151edcb15562c3559e9", "class_name": "RelatedNodeInfo"}, "3": {"node_id": "d5ff305a-1bc9-42fa-8a6b-5fe1ebe8e00d", "node_type": "1", "metadata": {}, "hash": "a65b7dc0b1631e8f02826883c6daa290b4988761143b06e96a56c7a6f29039e8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "```tsv\n[thead]A\t% immobilized body\n[thead]B\t% immobilized body\n[thead]C\t% immobilized body\n[thead]D\t% immobilized head\n[thead]\ttyramine concentration (mM)\ttime (min)\ttime (min)\ttime (min)\n[thead]\twild type\tser-2(pk1357)\twild type\tser-2(ok2103)\tser-2(pk1357)\tser-2 rescue\tunc-3\tunc-3 ser-2(pk1357)\tunc-3\tunc-3 ser-2(pk1357)\n[thead]\t0\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t10\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t20\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t30\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t40\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t50\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t60\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t70\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t80\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t90\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t100\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t110\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t120\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t130\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t140\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t150\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t160\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t170\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t180\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t190\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t200\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t210\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t220\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t230\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t240\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t250\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t260\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t270\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t280\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t290\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t300\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t310\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t320\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t330\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t340\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t350\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t360\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t370\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t380\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t390\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t400\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t410\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t420\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t430\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t440\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t450\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t460\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t470\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t480\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t490\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t500\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t510\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t520\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t530\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t540\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t550\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t560\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t570\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t580\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t590\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t600\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t610\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t620\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t630\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t640\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t650\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t660\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t670\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t680\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t690\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t700\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t710\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t720\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t730\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t740\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t750\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t760\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t770\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t780\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t790\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t800\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t810\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t820\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t830\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t840\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t850\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t860\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t870\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t880\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t890\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t900\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t910\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t920\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t930\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[t", 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[Donnelly2013, p.3, para 5](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "fa41fc9731582789f6a0c0f6231268312880f266e883366780c8af7c429ef3d4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t45700\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t45710\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t45720\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t45730\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t45740\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t45750\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t45760\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t45770\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t45780\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t45790\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t45800\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t45810\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t45820\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t45830\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t45840\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t45850\t0\t0\t0\t0\t0\t0\t0\t0\t0\n[thead]\t45860\t0\t0\t0\t0\t0\n```", "mimetype": "text/plain", "start_char_idx": 145429, "end_char_idx": 145984, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "46ce47b1-7c75-416e-b2df-938296ef7024": {"__data__": {"id_": "46ce47b1-7c75-416e-b2df-938296ef7024", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.4, para 0](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ba378ebc-3319-4e12-83aa-f124a1990554", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.4, para 0](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "4e3b87305f9307685a2e8f003142db026327da96722ea55c47ef10a3acffe787", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Monoaminergic Orchestration of a Complex Behavior", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 51, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "04e60d92-44a3-4c76-9e90-eadfbdb3a159": {"__data__": {"id_": "04e60d92-44a3-4c76-9e90-eadfbdb3a159", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.4, para 1](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ce46ef93-4c41-4f7b-ae09-1292d90372da", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.4, para 1](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "4c0f4245a08a698a10cd76526e7b669e303221b03ec3e5e2f0c5e34696febdce", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "that express the tyramine-gated chloride channel LGC-55 (Figure S3). *lgc-55* mutants fail to suppress head movements in response to touch, but head movements were suppressed normally in *ser-2* mutants, indicating that only LGC-55 is required for tyramine-induced head relaxation. The *ser-2* reporter was not expressed in interneurons that control locomotion, as expression did not overlap with *Pglr-1::GFP* and *Plgc-55::GFP* reporters that are expressed in the locomotion command neurons (unpublished data). *ser-2* reporter expression was also observed in 13 cells in the ventral cord (Figure 2A) that send commissures to the dorsal cord. The ventral cord is composed of excitatory cholinergic and inhibitory GABAergic motor neurons that innervate body wall muscles and control locomotion. Coexpression analysis with GFP reporters that specifically label cholinergic or GABAergic neurons showed that *Pser-2::mCherry* was highly expressed in a subset of GABAergic motor neurons (Figure 2B\u2013D). The same set of GABAergic motor neurons were labeled in transgenic line (*Pser-2a::GFP*) that expressed a reporter for the SER-2A isoform (unpublished data) \\[36]. GABAergic ventral nerve cord neurons are subdivided into 13 VD motor neurons that synapse onto the ventral body wall muscles, and 6 DD motor neurons that synapse onto the dorsal body wall muscles. The cells that highly express the *ser-2* reporter do not co-label with a *Pflp-13::GFP* reporter, which is expressed in the DD motor neurons (unpublished data) \\[37]. This indicates SER-2 is specifically expressed in the GABAergic VD motor neurons.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1609, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d27bb48b-8814-451b-a0f0-5b721b1c8931": {"__data__": {"id_": "d27bb48b-8814-451b-a0f0-5b721b1c8931", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.4, para 2](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7f6eda31-9955-4375-ac7d-86c5d1507a05", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.4, para 2](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "6a8c9e4c7182361fa3742e6a845bd895ad6f0e47cf948a6b8f57d8b2c584f4db", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Since GABAergic motor neurons are required for normal locomotion, we tested if SER-2 acts in these cells to mediate the inhibitory effects of tyramine on movement. No other promoters have been described that specifically drive expression in the GABAergic VD neurons. The complexity and size of the *ser-2* promoter did not allow us to define promoter elements that specifically drive expression in the VD neurons. We therefore expressed *ser-2* cDNA in all GABAergic neurons using the *unc-47* promoter (*Punc-47::SER-2*). *ser-2* expression in GABAergic neurons of *ser-2* mutants restored normal sensitivity to exogenous tyramine (Figure 2E).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 644, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c1b4ef96-c42f-43ed-add2-53de2ac048f6": {"__data__": {"id_": "c1b4ef96-c42f-43ed-add2-53de2ac048f6", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.4, para 3](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "521e10e5-3995-4aee-a4f5-50cc983fe9b4", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.4, para 3](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "f8da0a8b3df02d3906bc17fdd1154c7484028858bc579f9b483e87488ab88db0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "To determine if GABA signaling affects tyramine sensitivity, we tested GABA-deficient mutants for sensitivity to exogenous tyramine. We found that *unc-25* mutants, which lack glutamate decarboxylase required for GABA synthesis \\[38], were slightly hypersensitive to the immobilizing effects of exogenous tyramine (Figure 2E, Figure S4). This suggests that reduced GABA signaling increases the sensitivity to exogenous tyramine, likely through the hyperactivation of other tyramine receptors, such as LGC-55 and TYRA-2. GABA deficiency suppressed the resistance phenotype of *ser-2* mutants, since *unc-25; ser-2* double mutants were nearly as sensitive to tyramine as *unc-25* single mutants (Figure 2E). These epistasis experiments indicate that SER-2 acts upstream or in parallel to GABAergic signaling and are consistent with the hypothesis that SER-2 acts in the VD neurons to inhibit GABA signaling and control locomotion.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 928, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "298968d1-4ba2-4deb-aaff-7f0178b7c3a0": {"__data__": {"id_": "298968d1-4ba2-4deb-aaff-7f0178b7c3a0", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.4, para 4](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8de6a475-f180-460e-ba69-d54227961c88", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.4, para 4](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "8e85b064ad798f69afcb2aedb39467e84c8caf3c733915507ee9c7c8dd652f81", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We performed cell-specific rescue experiments to determine whether G-protein signaling components are required in the GABAergic neurons to mediate sensitivity to the exogenous tyramine. Expression of *goa-1* or *eat-16* in the GABAergic neurons (*Punc-47::GOA-1/G\u03b1o* and *Punc-47::EAT-16/RGS*) of *goa-1* and *eat-16* mutants, respectively, did not rescue the hyperactive locomotion phenotype. However, *goa-1* expression in GABAergic neurons of *goa-1* mutants largely restored sensitivity to exogenous tyramine (Figure 2E, Figure S4). Similarly, rescue expression of *eat-16* in GABAergic neurons partly restores sensitivity to exogenous tyramine. The activation of the G\u03b1q pathway in other cells may contribute to tyramine resistance phenotype in G-protein signaling mutants since the sensitivity to tyramine is not completely restored to wild-type levels. Nonetheless, the increased sensitivity of GABA-neuron-specific rescue of G-protein signaling mutants suggest that exogenous tyramine induces body immobilization through the activation of SER-2A and a G\u03b1o pathway in GABAergic neurons.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1093, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f6f6311d-cd56-4c7f-a7cd-4fa1e30780c2": {"__data__": {"id_": "f6f6311d-cd56-4c7f-a7cd-4fa1e30780c2", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.4, para 5](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "be5f0b7f-898f-4808-a0b7-6f572fda6fb4", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.4, para 5](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "597c55b97dd287c26ee421816b1e59b8dc468d90d550d62aa9dab756069ade0f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## SER-2 Inhibits Neurotransmitter Release", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 42, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b9bd188b-d5ff-4ef4-ac18-309e61925c29": {"__data__": {"id_": "b9bd188b-d5ff-4ef4-ac18-309e61925c29", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.4, para 6](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ffffe995-12ef-4166-b1c0-39c5562791bb", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.4, para 6](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "1a4e889efbd80e9789076c265bb284833fa40da55f840abcc2312db90d2146d4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "To test the hypothesis that SER-2 modulates neurotransmitter release from ventral cord motor neurons, we analyzed mutants for their sensitivity to the acetylcholinesterase inhibitor aldicarb. Aldicarb increases acetylcholine (ACh) concentration at the neuromuscular junction (NMJ), causing muscle contraction and eventual paralysis. Mutants with impaired ACh release are resistant to aldicarb-induced paralysis \\[39]. *egl-30/G\u03b1q* mutants are resistant to aldicarb, whereas *goa-1* mutants are hypersensitive to aldicarb-induced paralysis, indicating that EGL-30/G\u03b1q stimulates and GOA-1/G\u03b1o inhibits ACh release from motor neurons \\[31\u201333]. Since body wall muscles also receive inhibitory GABA inputs, hypersensitivity to aldicarb can also be caused by decrease in GABA release at the NMJ \\[40\u201342]. The time course of paralysis of *ser-2* mutants induced by aldicarb was similar to the wild-type (Figure 3A). This may be due to the restricted expression of *ser-2* in a subset of GABAergic neurons or insufficient endogenous tyramine signaling to modulate GABA release under regular assay conditions. We therefore generated transgenic lines that overexpressed *ser-2* in all cholinergic motor neurons (*Pacr-2::SER-2*) or GABAergic (*Punc-47::SER-2*) motor neurons and analyzed the rate of aldicarb-induced paralysis. In the absence of exogenous tyramine, the time course of paralysis of transgenic animals that express SER-2 in cholinergic or GABAergic ventral nerve cord motor neurons was similar to the wild-type (Figure 3A). However, on plates that contained both aldicarb and tyramine, animals that overexpressed *ser-2* in cholinergic neurons (*Pacr-2::SER-2*) were more resistant to the paralytic effects of aldicarb than the wild-type. Conversely, animals that overexpressed *ser-2* in all GABAergic neurons (*Punc-47::SER-2*) were hypersensitive to paralysis on plates containing aldicarb and tyramine (Figure 3B). These data are consistent with the hypothesis that SER-2 couples to the GOA-1/G\u03b1io pathway to inhibit neurotransmitter release.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2052, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "73a0ae4a-ac37-4066-8a06-4b1e0c174c29": {"__data__": {"id_": "73a0ae4a-ac37-4066-8a06-4b1e0c174c29", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.4, para 7](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a063f7bd-0110-41d2-8711-9fdf024c1c53", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.4, para 7](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "61ed2dc037c6c4a04079d592a25c943dec083db7915a091d1650de3fec741837", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Tyramine-Mediated Reduction in GABA Synaptic Release Requires SER-2", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 70, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1b8e30f1-8b73-45ef-bb1d-b624dc91e925": {"__data__": {"id_": "1b8e30f1-8b73-45ef-bb1d-b624dc91e925", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.4, para 8](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "48036f3c-6521-4f04-8aee-190405fe2a83", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.4, para 8](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "22537848c672a90de5cc2465cb68e63cbea22b8bf7119755db759f1ece1c251c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The GABAergic VD motor neurons that express *ser-2* make synaptic contacts onto the ventral musculature (Figure 4A). Therefore, to directly evaluate whether tyramine modulates synaptic release of GABA from motor neurons, we measured the frequency of endogenous inhibitory post-synaptic currents (IPSCs) in whole-cell recordings from ventral body wall muscle cells (Figure 3C\u2013H). To isolate GABA currents, recordings were made from *unc-29; acr-16* double mutants (+/+) that lack excitatory neurotransmission at the NMJ \\[43,44]. In *unc-29; acr-16* double mutants, the only remaining currents are mediated through chloride permeation of the GABAA-like receptor UNC-49 \\[43,45]. In these animals, we observed high levels of endogenous IPSC activity (\\~13 events/s) that gradually declined over the time course of the recording period (\\~10 min). This basal level of inhibitory activity is consistent with previous reports that have used other, nongenetic approaches to isolate IPSCs. After recording an initial 60 s period of basal activity, we switched to a bath solution containing tyramine. Within 30 s of tyramine exposure we noted a clear decrease in IPSC frequency (Figure 3E,G). The magnitude of this decrease was significantly greater than the slight decrease in IPSC frequency we observed", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1296, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f37d0179-b0c9-446a-a517-32c9ae721fc9": {"__data__": {"id_": "f37d0179-b0c9-446a-a517-32c9ae721fc9", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.5, para 0](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "03feb5e9-fba7-4e37-be2f-b3c1cd0dc45e", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.5, para 0](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "e93c1ca235708008bca7170eb57e73c9202fe299ab5520bb47f774e8d3dafb72", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Figure 2. *ser-2* is expressed in a subset of GABAergic motor neurons.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 72, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "636b6374-b4ee-4009-8707-14d310a5b653": {"__data__": {"id_": "636b6374-b4ee-4009-8707-14d310a5b653", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.5, para 1](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c76de170-b5d7-4cf6-842e-f706fa2e04dc", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.5, para 1](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "dd00a55accbe1efc1642dadc0ca5675af5debe751b4fb75ca31fdaa912ef3150", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "(A) A composite DIC image with fluorescent overlay showing that the *Pser-2::mCherry* transcriptional reporter is expressed in head muscles, head neurons, and neurons in the ventral nerve cord. (B\u2013D) Transgenic animal showing coexpression of *Pser-2::mCherry* (B) and *Punc-47::GFP*, which labels all GABAergic motor neurons (C). *Pser-2::mCherry* is strongly expressed in the GABAergic VD neurons but not the DD neurons (D). Anterior is to the left. Scale bar is 20 \u00b5m. (E) Exogenous tyramine induces immobilization though the activation of SER-2 and G\u03b1o signaling pathway in the GABAergic neurons. Shown is the percentage of animals that become immobilized after 10 min on 30 mM tyramine. Loss-of-function of *unc-25* (glutamic acid decarboxylase) suppresses the tyramine resistance of *ser-2* mutant animals. *unc-25* (GABA deficient) mutants and *unc-25; ser-2(pk1357)* double mutants are not resistant to the paralytic effects of exogenous tyramine. Expression of SER-2 in all GABAergic neurons (*Punc-47::SER-2*) restores sensitivity of *ser-2* mutants to exogenous tyramine. Expression of GOA-1/G\u03b1o or EAT-16/RGS in all GABAergic neurons (*Punc-47::GOA-1* or *Punc-47::EAT-16*) partially restores sensitivity to exogenous tyramine in the respective *goa-1* and *eat-16* mutants. Each bar represents the mean \u00b1 SEM for at least three trials, totaling a minimum of 30 animals.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1381, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b934f264-998b-4c62-8560-adfa68649053": {"__data__": {"id_": "b934f264-998b-4c62-8560-adfa68649053", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.5, para 2](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1ea703dc-b387-4792-9251-adf1f9e7ac80", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.5, para 2](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "b395d8bfcb7b2b7845b604259bc3eed8153ec941c60a5af7bda36a35f1699a22", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Label|% immobilized body|\n|-|-|\n|wild type|100|\n|unc-25|100|\n|unc-25; ser-2|100|\n|ser-2|45|\n|Punc-47::SER-2; ser-2|100|\n|goa-1|25|\n|Punc-47::GOA-1; goa-1|70|\n|eat-16|27|\n|Punc-47::EAT-16; eat-16|58|", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 199, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "26f18257-e6cd-43ee-a627-a10a57de2c07": {"__data__": {"id_": "26f18257-e6cd-43ee-a627-a10a57de2c07", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.6, para 0](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f0635d90-c3cf-4922-bb22-89703f4a9438", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.6, para 0](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "48c7acccf796a9a0a658fc22824bbccce2d899924e2a59c97cae16ff568ac5d0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Figure 3. Tyramine-mediated reduction in GABA synaptic release requires SER-2.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 80, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "87dd68a6-235e-4eed-8af6-927201699e58": {"__data__": {"id_": "87dd68a6-235e-4eed-8af6-927201699e58", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.6, para 1](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "352fd5f2-e7e3-4d7b-a175-3352e404f4c0", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.6, para 1](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "218831bf15b0c72d83703fc0a4c2187846cf94cf03d946487719441a75e84ec1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "(A, B) SER-2 expression in cholinergic (Pacr-2::SER-2) or GABAergic (Punc-47::SER-2) motor neurons alters the rate of paralysis of ser-2 mutants on aldicarb drug plates. All genotypes paralyze at a similar rate on drug plates containing only 0.5 mM aldicarb (A), yet drug plates containing both 30 mM tyramine and 0.5 mM aldicarb causes paralytic resistance.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 358, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d2acf0f1-4352-4aca-9fd9-69fe25fb2309": {"__data__": {"id_": "d2acf0f1-4352-4aca-9fd9-69fe25fb2309", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.6, para 2](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "07503e85-c3e6-4b2e-920d-c5f76bb356bc", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.6, para 2](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "bfb2cef725805dec58c70ce37160e6882ea5d48490dd13ae9cccf378607ec76a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## A", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "71648179-03c8-4328-a7a2-7f39a52f48d4": {"__data__": {"id_": "71648179-03c8-4328-a7a2-7f39a52f48d4", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.6, para 3](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bee698ac-1c3e-49eb-a79e-559003b22501", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.6, para 3](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "54702d791fe1f3aca3bc6f4c97fc43e3efac47bcf8cc239e0f1a28ee8a25b903", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "% paralyzed\n100\n80\n60\n40\n20\n0\n0 30 60 90 120 150 180 210\ntime (min)\nAldicarb", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 76, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "76bafcf2-e5c2-48ca-a875-a2fe1d87ccac": {"__data__": {"id_": "76bafcf2-e5c2-48ca-a875-a2fe1d87ccac", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.6, para 4](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "93431f65-10c0-4e4a-bd5c-b2181ebf0a5c", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.6, para 4](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "5e0e5261a5851f446eef2721e584a96074d8c2732af59e62914435bf6dd9a7e3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* wild type\n* ser-2(ok2103)\n* Punc-47::SER-2; ser-2\n* Pacr-2::SER-2; ser-2", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 74, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fcdb1efb-3b4b-4146-b04c-0a6ddd5c1f9e": {"__data__": {"id_": "fcdb1efb-3b4b-4146-b04c-0a6ddd5c1f9e", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.6, para 5](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "592e37c5-0e3d-46c8-a03e-437c07e22beb", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.6, para 5](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "9f0fe41c5eda4da624a30648408587884ca82d4d676733cb4d53a73c2238b661", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## B", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "66a63480-d593-472b-ac3a-05472110b9b4": {"__data__": {"id_": "66a63480-d593-472b-ac3a-05472110b9b4", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.6, para 6](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "174aa531-5068-4c4b-8ac8-1d6eb20a8c74", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.6, para 6](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "ce4da510ef285f1ff7b08d452ffee26daf8328d6406d161e68841bc5e371cf5d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "% paralyzed\n100\n80\n60\n40\n20\n0\n0 30 60 90 120 150 180 210\ntime (min)\nAldicarb\n\\&Tyramine", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 87, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7175cdcb-360f-4978-aa01-8f10ca796991": {"__data__": {"id_": "7175cdcb-360f-4978-aa01-8f10ca796991", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.6, para 7](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b7b3ebd1-ab78-4555-a8e1-f5433e92d62c", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.6, para 7](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "a3931f1fca5bf6af0c652c6e92710a75468a5a5380d8fe53980a2dbec357c5b3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "* wild type\n* ser-2(ok2103)\n* Punc-47::SER-2; ser-2\n* Pacr-2::SER-2; ser-2", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 74, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "873ccf94-5747-40b0-9681-34ab5e37bf92": {"__data__": {"id_": "873ccf94-5747-40b0-9681-34ab5e37bf92", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.6, para 8](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e42094f0-027b-4420-b24d-b1325c3a0213", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.6, para 8](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "31215c7f3f965603355f6d8d1e80d707de375b67397590d4963de32d9758ae78", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## C", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "281564e4-5a20-489b-979a-1a6c8aadbf4d": {"__data__": {"id_": "281564e4-5a20-489b-979a-1a6c8aadbf4d", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.6, para 10](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e6cd1d00-2e30-4eec-a8f8-61b876511f84", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.6, para 10](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "8d2835dbd981a8f245534dde20c6d624bb2c7f48c452455f3ed80824a4ad28b2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## D", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7f9024d4-7860-4cd7-9662-4e154f97424a": {"__data__": {"id_": "7f9024d4-7860-4cd7-9662-4e154f97424a", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.6, para 13](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7a0b6c3b-c040-4416-90d5-2873ffdfbd75", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.6, para 13](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "5492a63b5538cfc748e54541b3a858ac04ffdd8794b4047bc3cb662e176aac2c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## E", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5b84fbdf-2722-4bf8-9532-112905261a9f": {"__data__": {"id_": "5b84fbdf-2722-4bf8-9532-112905261a9f", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.6, para 16](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "407c943e-97f8-4c9d-b026-d609f2620c83", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.6, para 16](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "2b54eed3b98372d7b3bff7de282853913377f3091dd2fc9350654442bed500f2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## F", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "bd2a5ffd-de33-4f6a-9d75-186213ef4eb8": {"__data__": {"id_": "bd2a5ffd-de33-4f6a-9d75-186213ef4eb8", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.6, para 17](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "46d9a4af-9643-4db3-ba57-16e8e7681163", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.6, para 17](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "586708a1d08c9c71503c707a46ff0025fdb8e73103f06d649ef91133c602184c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Frequency (Hz)\n20\n15\n10\n5\n0\n0 25 50 75 100 125\nTime (s)\nser-2\n\u2191", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 63, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0af00845-1d0d-49ed-87e0-484fb8f9880d": {"__data__": {"id_": "0af00845-1d0d-49ed-87e0-484fb8f9880d", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.6, para 18](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "dd3a4ccc-92f3-46b3-8731-7539c6c12f4f", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.6, para 18](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "bd34534426cda128751676393761174401942303816aa43e633192e2e21d96e3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## G", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8584c866-9475-42da-8cd9-af82931d1fa3": {"__data__": {"id_": "8584c866-9475-42da-8cd9-af82931d1fa3", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.6, para 23](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "12f245b8-f0f5-4423-8a04-82f732e6cc0e", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.6, para 23](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "f1daeeaa6c52ae56ed9179020487cf1541017368a1bfab3a082448a7a59521f6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## H", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "96a33f5e-b3d9-49b5-b3fb-761408834f45": {"__data__": {"id_": "96a33f5e-b3d9-49b5-b3fb-761408834f45", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.6, para 26](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a97da5df-5b9f-4c9f-9ad0-acbe6aa6d605", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.6, para 26](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "dcec34c5c9efe34a659d77677dbbaae5547b8127f738a4a06a092a1578ad3e91", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Time (s)|Relative Frequency after Tyramine (%)|Relative Amplitude after Tyramine (%)|\n|-|-|-|\n|0|75|90|\n|25|15|90|\n|50|18|90|\n|75|12|90|\n|100|10|90|\n|125|10|90|", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 161, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "028c306e-ae85-4835-8f29-4bbaf3e43d2b": {"__data__": {"id_": "028c306e-ae85-4835-8f29-4bbaf3e43d2b", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.7, para 0](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4e7bf360-9292-4a05-9014-70a7ab7ae892", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.7, para 0](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "317d980edf65e83f971e8043667a7f9952d50e0c4e88ca4c71bb6e3fad7b7ea5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "(Pacr-2::SER-2) or hypersensitivity (Punc-47::SER-2) (B). Aldicarb experiments were conducted on nematode growth media (NGM) plates. 30 mM tyramine dissolved in NGM agar does not inhibit locomotion. SER-2 was expressed in ser-2(pk1357) mutant animals. Each data point represents the mean percentage of animals immobilized by aldicarb scored every 30 min \u00b1 SEM for at least four trials, totaling a minimum of 60 animals. (C, D) Representative endogenous inhibitory postsynaptic currents (IPSCs) recorded from ventral body wall muscles. +/+, unc-29; acr-16 double mutants that lack excitatory neurotransmission at the NMJ are wild-type for the ser-2 locus. ser-2, unc-29; acr-16; ser-2(pk1357) triple mutants. (E, F) Tyramine application decreased the rate of IPSCs in +/+ (n = 6), but not ser-2 mutants (n = 5). Arrow depicts tyramine application time point. Each point represents the IPSC frequency calculated over a 5-s time window as indicated. The red points correspond to the displayed samples in (C) and (D), respectively. Dashed lines show average frequency before tyramine application and during the stabilized tyramine response period. (G) Average IPSC frequency after tyramine application plotted relative to IPSC frequency prior to tyramine exposure. Values were normalized to average frequency observed in control recordings in the absence of tyramine. (H) Average amplitude of IPSCs after tyramine application plotted relative to average amplitude prior to tyramine exposure. Error bars depict SEM. Statistical differences calculated from +/+: \\*p<0.05, two-tailed Student's t test. doi:10.1371/journal.pbio.1001529.g003", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1632, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "902ea3a3-f4d9-4406-9c1c-735d9be2334e": {"__data__": {"id_": "902ea3a3-f4d9-4406-9c1c-735d9be2334e", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.7, para 1](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b1a7eaf7-29ba-465e-b28e-a03d007f62fb", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.7, para 1](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "83805fbbcd4a8473f3ff0340c74f20268160e55707ae599cd853d9dd0efe5272", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "over the same time course in control experiments without tyramine (+ tyramine, 34% \u00b1 4% decrease; no tyramine, 13% \u00b1 6% decrease). These results indicate that tyramine can inhibit GABA-mediated transmission at the NMJ. The tyramine-induced reduction was not reversible within the time course of our recordings, which may suggest that tyramine is acting through a high affinity receptor. To test whether the reduction in IPSC frequency involved SER-2, we examined the effects of tyramine", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 486, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a6594e76-aa91-409a-9d93-633fa3ffbff8": {"__data__": {"id_": "a6594e76-aa91-409a-9d93-633fa3ffbff8", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.7, para 5](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6e97b5f3-56eb-4121-bbcf-ddc4e39129b5", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.7, para 5](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "17923abf11c56c806a7f4686a3e13b63e22ea6c35b473bf513ceb1bcab5d5a7a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "| strain         | direction (\u00b0/sec) | (n) |\n| -------------- | ----------------- | --- |\n| VD ablated     | 4\u00b0 \u00b1 1 \\*         | 8   |\n| DD ablated     | -14\u00b0 \u00b1 2 \\*\\*\\*   | 13  |\n| mock ablated   | -1\u00b0 \u00b1 1           | 46  |\n| wild type      | -1\u00b0 \u00b1 1           | 43  |\n| unc-25(e156)   | 2\u00b0 \u00b1 1            | 57  |\n| ser-2 (pk1357) | -1\u00b0 \u00b1 1           | 32  |\n| ser-2 (ok2103) | -1\u00b0 \u00b1 1           | 21  |", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 404, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "febdeb87-bd94-459d-ab05-b8bedc7df825": {"__data__": {"id_": "febdeb87-bd94-459d-ab05-b8bedc7df825", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.7, para 8](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "aac1fa9b-455d-46c5-9328-ec03b32c4b60", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.7, para 8](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "2df887f5d165cbc5abaa502682f0871b70cbb85f43d9878dd363b2c3797a1e9d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Figure 4. Ablation of VD or DD motor neurons induces a navigational bias. (A) Schematic of D-motor neuron wiring. VD motor neurons receive inputs from cholinergic DB motor neurons, and release GABA on ventral body wall muscles. DD motor neurons receive input from cholinergic VB motor neurons and release GABA on dorsal body wall muscles. Figure adapted from wormatlas.org. (B, C) Killing subsets of GABAergic motor neurons by laser ablation-induced navigational biases. (B) Turning rate (\u00b0/sec \u00b1 SEM) is affected in animals where VD or DD neurons are ablated. DD-ablated animals navigate with a dorsal bias. VD-ablated animals navigate with a ventral bias. Mock-ablated animals, GABA-deficient mutants (unc-25), and ser-2 mutants did not show a change in turning rate. Turning angle was calculated by worm tracking software; n is indicated. (C) Representative locomotory path of a DD-ablated (left panel) and VD-ablated animal (right panel). DD-ablated animals locomote in dorsally directed circles (Movie S1). VD-ablated animals locomote in ventrally directed circles (Movie S2). The direction of locomotion (\u00b0) was determined from orientation of the animal's trajectory on the plate (inset). Red line traces the path of locomotion from the origin (black dot); yellow arrow designates the ventral side of the animal. Instantaneous turning angle is plotted for the duration of the locomotion path. Statistical differences calculated from mock ablations: \\*p<0.05, \\*\\*\\*p<0.001, two-tailed Student's t test. doi:10.1371/journal.pbio.1001529.g004", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1546, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8d610100-a6d5-42c4-8273-1b0fd3fbc60b": {"__data__": {"id_": "8d610100-a6d5-42c4-8273-1b0fd3fbc60b", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.8, para 0](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bd23d6ea-3842-4e5c-af4f-fccb397e20ad", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.8, para 0](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "97af945d995ecda1662ac79ae900779ddd771005cc99ae17aff5247717fc4367", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Monoaminergic Orchestration of a Complex Behavior", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 51, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8c762b7a-a138-42f5-8841-7c8d65db2023": {"__data__": {"id_": "8c762b7a-a138-42f5-8841-7c8d65db2023", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.8, para 1](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5140c94a-d68d-4d06-b96c-130876c69a41", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.8, para 1](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "572c4da96637c6cd325e371241ab5104464893fc302955d34bab1febcf06cdc1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "exposure in recordings from *unc-29; acr-16; ser-2* triple mutants (Figure 3F,G). The amplitude of endogenous GABA IPSCs was not significantly different between +/+ animals and *ser-2* mutants (+/+, 29.5\u00b11.4 pA; *ser-2*, 31.9\u00b13.9 pA) and was not significantly affected by tyramine exposure for either strain (+/+, 26.9\u00b11.2 pA; *ser-2*, 30.7\u00b14.4 pA), indicating that clustering and function of postsynaptic GABA receptors are normal in *ser-2* mutants, and not affected by tyramine (Figure 3H). The basal IPSC frequency prior to tyramine exposure was also not changed significantly in *ser-2* mutants (+/+, 13.2\u00b11.2 Hz; *ser-2*, 12.5\u00b12 Hz). However, the tyramine-mediated reduction in IPSC frequency we observed in +/+ animals was significantly attenuated in *ser-2* mutant animals (*ser-2*, 17%\u00b14% reduction; +/+, 35%\u00b14% reduction) such that it was indistinguishable from that observed in our control recordings without tyramine (control (no tyramine), 13%\u00b16% reduction). After normalization, tyramine application reduced IPSC frequency by 25%\u00b15% in +/+ compared to 5%\u00b15% reduction in *ser-2* mutants (Figure 3G). Taken together, our data show that tyramine inhibits GABA release onto ventral body wall muscles in a SER-2-dependent manner.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1239, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b30c09c8-8b9d-4d14-9999-e2e35903c4d3": {"__data__": {"id_": "b30c09c8-8b9d-4d14-9999-e2e35903c4d3", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.8, para 2](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1540101c-1fd8-409c-8c4c-32570d39da7f", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.8, para 2](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "c30cd90503b6bb2d8af6c8870fc3f8593079c726b9f732c903de05f351d368c5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Ablation of Subsets of GABAergic Motor Neurons Induces a Navigational Bias", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 77, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e14ae982-528f-4ac9-a046-f76d812b9b4e": {"__data__": {"id_": "e14ae982-528f-4ac9-a046-f76d812b9b4e", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.8, para 3](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "76163204-ffef-46a5-804b-071b94dfbe51", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.8, para 3](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "781847372e3a36c72f3649073ed57b0666a2cac7b2b45b661b765d51f27537ce", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "*C. elegans* moves on its side by propagating a sinusoidal wave of ventral-dorsal flexures along the length of its body. GABAergic VD motor neurons synapse onto ventral muscles and receive synaptic inputs from DA/DB cholinergic motor neurons that synapse onto dorsal body wall muscles (Figure 4A) \\[46]. Conversely, GABAergic DD motor neurons synapse onto dorsal muscles and receive synaptic inputs from VA/VB cholinergic motor neurons that synapse onto ventral body wall muscles. This arrangement suggests that a body bend is generated by Ach-mediated muscle contraction on one side and GABA-mediated relaxation on the contralateral side. This hypothesis is supported by the observation that animals in which the VD and DD neurons are killed by laser ablation move with a reduced wave amplitude \\[46]. The *Pser-2::GFP* and *Pflp-13::GFP* fluorescent markers, which specifically label the 13 VD and 6 DD neurons, respectively, allowed us to further test the role of the VD and DD neurons in laser ablation experiments. Animals in which only the VD neurons were ablated still propagated a sinusoidal wave along the anterior\u2013posterior axis, but displayed deeper ventral than dorsal flexures (Movies S1 and S2). As a consequence VD ablated animals moved in ventrally directed circles (radius 2.20\u00b10.29 body lengths, *n* = 5, Figure 4B,C). Conversely, animals in which the DD neurons were ablated exhibited deeper dorsal than ventral flexures and moved in dorsally directed circles (radius 0.61\u00b10.11 body lengths, *n* = 10). GABA-deficient *unc-25* mutants made shallow body bends, but showed no directional bias in their locomotion pattern. Thus, the specific ablation of the VD or DD GABAergic neurons indicate that asymmetric relaxation of either the ventral or dorsal body wall muscles results in a directional bias in locomotion.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1831, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7ffa69da-0d6a-4008-b36a-74d6937596ac": {"__data__": {"id_": "7ffa69da-0d6a-4008-b36a-74d6937596ac", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.8, para 4](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "055f92ca-150d-4b8d-ada4-170d9de7947d", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.8, para 4](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "8b9cea961071571411627174845f19831a46bb05368979f0b96e3738d4d95390", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Induction of Turning Behavior Through Optogenetic Control of GABAergic Motor Neurons", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 87, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a2bb8981-dfb8-42ab-8d2e-5afd83cca201": {"__data__": {"id_": "a2bb8981-dfb8-42ab-8d2e-5afd83cca201", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.8, para 5](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bcd584ea-c44b-4195-afe9-f8086280c122", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.8, para 5](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "b33ef2c9997ee7589486a6c492370f979eb59ce85b5b5a6b830f3e7d94d424e9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Our data suggest that the modulation of the activity of either the VD or DD motor neurons allows the animal to bend and steer in either a ventral or dorsal direction. To determine if acute activation or inhibition of a specific subclass of GABAergic neurons could induce turning behavior, we used optogenetic stimulation and inhibition. The complexity of the *ser-2* promoter, which contains coding sequences and alternative start sites, did not allow us to highly express light-activated channels in the VD neurons. To test whether the differential activity of the VD and DD motor neurons can induce bending, we generated transgenic animals that co-expressed the light-activated cation channel Channelrhodopsin-2 (ChR2) \\[47] and light-activated chloride pump Halorhodopsin (NpHR) \\[48] in the six GABAergic DD motor neurons that synapse onto the dorsal muscles (*Pflp-13::ChR2; Pflp-13::NpHR*). ChR2 is activated by blue light and depolarizes neurons, while NpHR is activated by green light and hyperpolarizes neurons. We found that blue light activation induced a deep ventral turn (Figure 5 and Movie S3). In contrast, green light inhibition induced a deep dorsal turn. This turning behavior was not observed in nontransgenic animals or in transgenic animals raised on plates without all-trans-retinal, the chromophore of ChR2 and NpHR. To quantify turning behavior we calculated a bending index as the fraction of animals that turned ventrally or dorsally in response to light exposure (Figure 5A). A bending index of zero indicates no directional bias, whereas a negative or positive fraction indicates a ventral or dorsal bias, respectively. The bending index of *Pflp-13::ChR2/NpHR* transgenic animals was \u22120.45\u00b10.04 with exposure to blue light and 0.41\u00b10.06 for animals with exposure to green light. The *flp-13* promoter also drives expression in a small set of head neurons in addition to the DD neurons. To determine if the activation or inhibition of the DD neurons was sufficient to induce bending, we used an optogenetic illumination system capable of tracking and stimulating individual regions of a freely moving animal \\[49]. Targeted illumination of the animal\u2019s ventral nerve cord that harbors the DD neuronal cell bodies induced a tight ventral bend in response to blue light activation and a tight dorsal bend in response to green light inhibition (Figure 5B and Movie S3). Switching between blue and green light exposure enabled the remote control of ventral and dorsal turning behavior in freely moving *Pflp-13::ChR2/NpHR* transgenic animals. Thus, the acute stimulation of GABA release on the dorsal side induced relaxation of the dorsal muscles resulting in a ventral turn. Conversely, the acute inhibition of GABA release onto the dorsal muscles resulted in hypercontraction of dorsal muscles and a dorsal bend. Our data indicate that modulating the activity of subsets of GABAergic neurons synapsing onto either the dorsal (DD) or ventral side (VD) of the animal can induce navigational bias.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 3021, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "935e82ff-eaaf-48ae-8744-52352cf82e4b": {"__data__": {"id_": "935e82ff-eaaf-48ae-8744-52352cf82e4b", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.8, para 6](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1abe9f50-7486-4ce0-8bf4-d70285829a02", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.8, para 6](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "ccfaab43b0d401102976937e6081e286d503e4b1cf8420adbc79deb30e2300dd", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## *ser-2* Facilitates the Execution of Omega Turns in the Escape Response", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 74, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ce958c20-c7d0-4a43-af11-9d563a65f4e3": {"__data__": {"id_": "ce958c20-c7d0-4a43-af11-9d563a65f4e3", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.8, para 7](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "51752c06-51b1-45ee-8edf-a72950a67fc7", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.8, para 7](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "9b5ab1ebfd6016505e89179ba81c0b26d7696d104604561d0ea66f70552be4b6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The expression of *ser-2* in the GABAergic VD neurons suggested a possible role in *C. elegans* navigation. However, *ser-2* mutants moved normally and did not display a ventral or dorsal directional bias (Figure 4B) possibly through a lack of basal tyramine to activate SER-2 during regular locomotion. We have previously shown that tyramine coordinates the timing of backing locomotion and the suppression of head movements in the escape response \\[13]. Gentle anterior touch triggers tyramine release from the RIM neurons and the synaptic activation of the tyramine-gated chloride channel, LGC-55 \\[22]. Is SER-2 also required in the execution of the escape response? Touch-induced reversals are often coupled to a sharp omega turn, which allows the animal to change locomotion in a direction opposite to its original course (Figures 6E and 7A) \\[18]. The omega turn is initiated by a steep ventral bend of the head when the animal reinitiates forward locomotion. While the sharp bend is propagated posteriorly along the body, the head usually slides along the ventral side of the body. We analyzed turning behavior in response to gentle anterior touch. We found that the likelihood of engaging in an omega turn (>90\u00b0 turn initiated by the first forward head", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1261, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "95922dc7-ac8b-4d1e-84f6-90ff9c08d682": {"__data__": {"id_": "95922dc7-ac8b-4d1e-84f6-90ff9c08d682", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.9, para 0](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "531ca953-df1d-41c0-8ded-35726919cdb0", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.9, para 0](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "a6ee0b730a2c071b33a5ad368aae4944fcd245be7ae9d5d823245714ccccb0eb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Figure 5. Optogenetic control of navigation. (A, B) Acute modulation of the activity of DD GABA neurons in transgenic animals expressing channelrhodopsin (ChR2) and halorhodopsin (NpHR) in DD motor neurons (*Pflp-13::ChR2::GFP; Pflp-13::NpHR::CFP*) induces turning behavior. Blue light activation of GABAergic DD motor neurons that synapse onto dorsal muscles induces ventral turning. Green light inhibition of GABAergic DD motor neurons induces dorsal turning. (A) Quantification of bending behavior with green and blue light exposure. Bending bias was calculated as the fraction of dorsal turns \u2013 fraction of ventral turns after blue (DD activation, blue bars) or green (DD inhibition, green bars) light exposure. Each bar represents the mean bending bias for a minimum of 45 animals per genotype. Statistical significance as indicated: \\*\\*p<0.001 and \\*\\*\\*p<0.0001, two-tailed Student's t test. (B) Locomotion traces signify the time course of blue and green light exposure during forward movement (red). Open circles denote 1-s time marks. The compass indicates anterior (A), posterior (P), ventral (V), and dorsal (D) directions. Kymographs display sinusoidal bending wave amplitude before, during, and after light exposure. Normalized curvature is plotted at each point along the worm's centerline in units of inverse worm lengths. Color indicates curvature in either the ventral (red) or dorsal (blue) direction. The colored bands widen and brighten during deep turns induced by light exposure: white horizontal dotted lines indicate duration of light exposure, Ventral indicates a deep ventral bend, and Dorsal indicates a deep dorsal bend. Still images were taken at \\* location on worm track (Movie S3). Yellow triangle indicates the position of the vulva. doi:10.1371/journal.pbio.1001529.g005", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1808, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cb21d068-06bd-4291-8f33-bb8102be7698": {"__data__": {"id_": "cb21d068-06bd-4291-8f33-bb8102be7698", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.9, para 1](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f4f89857-b071-4d84-b9eb-94f88c6a1c9f", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.9, para 1](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "2b12aa2c9bd260c98d6e01a7e017d5db608f465d4b318149d464b95006da88e9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## A", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 4, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "db515b66-fc91-4ad6-a509-fa53c2773e35": {"__data__": {"id_": "db515b66-fc91-4ad6-a509-fa53c2773e35", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.9, para 2](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3cd3418a-93b9-4adf-843a-602ac24776ca", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.9, para 2](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "eb7d40cc8665e0cac379faf6eb1ab0eb1cd7b71becdd91867d04e4fa19aef397", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|bending index|Dorsal|Ventral|\n|-|-|-|\n|-0.6|-|-|\n|-0.4|-|-|\n|-0.2|-|-|\n|-0.0|-|-|\n|0.2|-|-|\n|0.4|-|-|\n|0.6|-|-|\n\n|retinal|-|+|-|+|-|+|-|+|\n|-|-|-|-|-|-|-|-|-|\n|DD-ChR2/NpHR|-|-|+|+|-|-|+|+|\n## B", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 195, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4b350bee-212d-4551-9785-bc9e69e408c5": {"__data__": {"id_": "4b350bee-212d-4551-9785-bc9e69e408c5", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.9, para 3](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "12546720-fa35-4ae7-95be-adfd62daac86", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.9, para 3](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "554290a508d8206125f7738902009dc741df7fca6a20061154cc44a9b664db67", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Note:** The figure contains two kymographs and a central diagram showing locomotion traces. The kymographs are on the left and right sides, with the central diagram showing the worm's movement path. The kymographs display normalized curvature over time, with color indicating curvature direction (red for ventral, blue for dorsal). The central diagram shows the worm's path with light exposure indicated by white horizontal dotted lines. The compass indicates anterior (A), posterior (P), ventral (V), and dorsal (D) directions. The yellow triangle indicates the position of the vulva.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 587, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3487f7fd-5236-4ddf-8b97-2c2a60f91e2e": {"__data__": {"id_": "3487f7fd-5236-4ddf-8b97-2c2a60f91e2e", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.9, para 4](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d7eea216-559b-4584-832d-d33b34632413", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.9, para 4](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "e9b3149c3b03066eb37f11cfaa8343abe4b8996fc8337ac5f382ff3f993e3592", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|time (s)|normalized curvature|\n|-|-|\n|-1|+10|\n|0|+5|\n|1|0|\n|2|-5|\n|3|-10|\n\n|time (s)|normalized curvature|\n|-|-|\n|-1|+10|\n|0|+5|\n|1|0|\n|2|-5|\n|3|-10|", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 150, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b77a6a74-70b5-40bd-a774-9dcd38f010de": {"__data__": {"id_": "b77a6a74-70b5-40bd-a774-9dcd38f010de", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.10, para 0](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b4804b7c-bbcf-4ba4-95cf-ca70abcfbcf2", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.10, para 0](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "e32a52041eb204917ffa485c48870f34b831eea28ae27036b381c12800ddf743", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Figure 6. ser-2 mutants make shallow omega bends.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 51, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0b15ac16-f3b3-4263-b139-d023d6f0041a": {"__data__": {"id_": "0b15ac16-f3b3-4263-b139-d023d6f0041a", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.10, para 1](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8a2889f3-919a-469a-8d5d-7f7ddd6bf785", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.10, para 1](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "b61f0b760b862f80d82894852303ab82ae38fe998575ca37349c11b44bdafb79", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "(A) Distribution of touch-induced reversals ending in an omega turn. Omega turns are more likely to occur after longer reversals (>3 body bends). Wild-type and ser-2 mutant animals initiate omega turns at the same rate (n\u2265150 per genotype).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 240, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d4dd2210-dc6e-48da-8158-42075a01233c": {"__data__": {"id_": "d4dd2210-dc6e-48da-8158-42075a01233c", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.10, para 2](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0c72d5a8-512a-48e4-ad8b-152d1db444dd", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.10, para 2](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "8d6108fcc2ee7195642294372ab6fb63ce1cbbff0d97a0f84567e4333e0663d8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "(B) Schematic representation of the omega angle. The omega angle was measured as the angle from the deepest point in the ventral bend to the closest points anterior and posterior of the animal. Images were adapted from movies of animals in the most ventrally contracted state of the escape response.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 299, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "badb566b-727a-4ca9-852b-521f810a0762": {"__data__": {"id_": "badb566b-727a-4ca9-852b-521f810a0762", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.10, para 3](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7f8a336c-99ad-40fc-856b-7e4f4c21e44d", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.10, para 3](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "3391fa33c8757f6b4a400bf05a3f952a2c30d4952ab723c76cd203267ff3a62e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "(C) Percent of omega turns where the animal's nose touches the tail during the execution of the turn (closed omega turn). ser-2 mutants \\[ser-2(ok2103), n = 52; ser-2(pk1357), n = 62] touch nose to tail less frequently than wild-type (n = 51) in omega turns induced by both touch (Movies S4 and S5) and blue light in a Pmec-4::ChR2 background \\[Pmec-4::ChR2, n = 38; ser-2(ok2103); Pmec-4::ChR2, n = 43; ser-2(pk1357); Pmec-4::ChR2, n = 28]. Tyramine/octopamine-deficient tdc-1 mutants touch nose to tail less frequently than wild-type \\[tdc-1(n3420), n = 144], while", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 567, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "74008987-7ea8-44b0-9b81-724a7807a9d6": {"__data__": {"id_": "74008987-7ea8-44b0-9b81-724a7807a9d6", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.10, para 4](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ddfdd1cc-414f-48eb-b7a8-ae132ab5387c", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.10, para 4](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "a4d60687efd45d3ce8a10ec250c5e99d79c4fe00b4e4b7b25cb424485947d4b3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "(D) Omega angle in degrees. The omega angle was measured as described in (B). The data show that ser-2 mutants have a significantly smaller omega angle compared to wild-type, indicating shallower omega turns.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 208, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d660b0fc-32fb-4c00-b3d3-028a9d552120": {"__data__": {"id_": "d660b0fc-32fb-4c00-b3d3-028a9d552120", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.10, para 5](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2872d97c-ffd8-4806-a728-1f689013f2cc", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.10, para 5](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "402f839c335b713704fbc2ca4df3750cd847d11e7413c5521832b282a26528db", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "(E) Schematic representation of the escape angle. The escape angle is defined as the angle between the direction of the initial forward movement and the direction of the escape response. The diagram shows the dorsal and ventral sides of the animal, with the escape angle measured from the dorsal side.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 301, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a8361e6a-e6ec-473c-8c40-7902647168d6": {"__data__": {"id_": "a8361e6a-e6ec-473c-8c40-7902647168d6", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.10, para 6](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2951ef48-4daa-4186-9562-fc015421ddb2", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.10, para 6](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "17579e4ba93cf40df0d452b0091f44ab9c65e45a7184420e8767a1b0da477c1d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "(F) Scatter plot of the angle of escape in degrees for various genotypes. The data show that ser-2 mutants have a significantly different escape angle compared to wild-type, with a mean angle of 179\u00b0\u00b15\u00b0 for wild-type and 157\u00b0\u00b15\u00b0 for ser-2(ok2103), 150\u00b0\u00b15\u00b0 for ser-2(pk1357), 173\u00b0\u00b17\u00b0 for ser-2 rescue 2, 168\u00b0\u00b15\u00b0 for ser-2 rescue 3, 143\u00b0\u00b16\u00b0 for tdc-1, and 177\u00b0\u00b111\u00b0 for tbh-1.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 373, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a605166a-33cb-4b9b-9df2-66cab57774ac": {"__data__": {"id_": "a605166a-33cb-4b9b-9df2-66cab57774ac", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.10, para 7](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8be7fbe0-df51-4896-ade3-b9af64afe9da", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.10, para 7](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "8997d7471484c31c489a5c9ca3260771663254b69ca9ec0febe9366e5d1b0c27", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|genotype|omega angle (degrees)|\n|-|-|\n|wild type|179\u00b15|\n|ser-2(ok2103)|157\u00b15|\n|ser-2(pk1357)|150\u00b15|\n|ser-2 rescue 2|173\u00b17|\n|ser-2 rescue 3|168\u00b15|\n|tdc-1|143\u00b16|\n|tbh-1|177\u00b111|\n\n|genotype|% omega turns with nose to tail touch|\n|-|-|\n|wild type|85|\n|ser-2(ok2103)|35|\n|ser-2(pk1357)|25|\n|ser-2 rescue 2|70|\n|ser-2 rescue 3|55|\n|tdc-1|30|\n|tbh-1|20|\n\n|genotype|number of backward body bends|% omega turns after reversal|\n|-|-|-|\n|wild type|1|5|\n|wild type|2|10|\n|wild type|3|20|\n|wild type|4|40|\n|wild type|5|60|\n|wild type|6+|85|\n|ser-2|1|0|\n|ser-2|2|10|\n|ser-2|3|20|\n|ser-2|4|50|\n|ser-2|5|55|\n|ser-2|6+|85|", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 605, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d475bcec-7e8c-4387-8dcb-d9d7b676b111": {"__data__": {"id_": "d475bcec-7e8c-4387-8dcb-d9d7b676b111", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.11, para 0](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3dce445e-2baf-4333-814b-4268a1d73b06", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.11, para 0](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "17a11e836eab910cf353b7a985036ab4abc23b1ea0c84c1f9b33727e540b4449", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "octopamine-deficient tbh-1 mutants close omega turns like the wild-type \\[tbh-1(n3247), n=153]. Genomic rescue lines partially restore this omega turning defect (ser-2 rescue line 2, n=20; ser-2 rescue line 3, n=21). (D) Average omega angle measured after touch or exposure to blue light in a Pmec-4::ChR2 background \\[Pmec-4::ChR2, n=38; Pmec-4::ChR2; ser-2(ok2103), n=43; Pmec-4::ChR2; ser-2(pk2103), n=28]. ser-2 mutants \\[ser-2(ok2103), n=52; ser-2(pk1357), n=62] and tyramine/octopamine-deficient mutants \\[tdc-1(n3420), n=35] make a wider omega turn than wild-type (n=51). Octopamine-deficient tbh-1 mutants do not make wider omega turns \\[tbh-1(n3247), n=16]. Genomic rescue lines partially restore the omega angle defect of the mutants (ser-2 rescue line 2, n=20; ser-2 rescue line 3, n=21). (E) Escape angles were measured from the direction of the reversal (induced by gentle anterior touch) to the direction of reinitiated forward locomotion. (F) Distribution of escape angles. Dashed grey line indicates average. Wild-type animals and tbh-1 mutants escape in the opposite direction from the touch stimulus \\[wt, 179^\\circ \\pm 5^\\circ, n=42; tbh-1(n3427), 177^\\circ \\pm 11^\\circ, n=16]. ser-2 mutants and tdc-1 mutants make a shallower escape angle \\[ser-2(ok2103), 157.5^\\circ \\pm 5^\\circ, n=53; ser-2(pk1357), 150^\\circ \\pm 5^\\circ, n=46; tdc-1(n3420), 143.3^\\circ \\pm 6^\\circ, n=35]. Genomic rescue lines restore the escape angle to wild-type levels (ser-2 rescue line 2, 173^\\circ \\pm 7^\\circ, n=12; ser-2 rescue line 3, 168.5^\\circ \\pm 5^\\circ, n=20). Rescue denotes the transgenic line Pser-2::SER-2; ser-2(pk1357)). Error bars depict SEM. Statistical differences calculated from wild-type unless otherwise indicated: \\*p<0.05, \\*\\*p<0.01, \\*\\*\\*p<0.001, two-tailed Student's t test. doi:10.1371/journal.pbio.1001529.g006", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1838, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f1ea8d4b-86d9-4390-834e-73c4b61b7e44": {"__data__": {"id_": "f1ea8d4b-86d9-4390-834e-73c4b61b7e44", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.11, para 1](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "725dbc6a-1644-44a1-b737-28232c2493f3", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.11, para 1](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "e6a391cec1e9f22e9fdf47f3a189b9aa332943a86463969111a0e5628d6fd6fd", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "swing) was correlated with the length of the reversal (Figure 6A). Short reversals most often resulted in shallow head bends and modest deflections from the original trajectory. In contrast, escape responses that included reversals of four or more body bends most often ended in an omega turn. These results are consistent with previous studies of reversals where omega turns tend to occur after a long reversal \\[50\u201352].", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 421, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4db54deb-5b5f-4578-904a-af46c6ccf3dc": {"__data__": {"id_": "4db54deb-5b5f-4578-904a-af46c6ccf3dc", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.11, para 2](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bb1b5c66-5f87-479a-bbf3-d672eadc70ed", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.11, para 2](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "1e2066d9046d5229f6aabc234fc187ecc9b6e54edd1da79664e6488d57eae253", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Omega turns that occurred in response to anterior touch were exclusively made on the ventral side of the animal (n \\ge 250). In response to touch, animals in which the GABAergic DD neurons", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 188, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "76c807ba-cf12-434f-9e89-81a902969599": {"__data__": {"id_": "76c807ba-cf12-434f-9e89-81a902969599", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.11, para 3](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f5dfbbd2-2999-446c-ab30-62b8f0540736", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.11, para 3](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "3737dc2476ff7e0d336aedfdfe67e232d009aa2a3a68370ac590378259ebd2f1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Figure 7. Model: Tyramine orchestrates the C. elegans escape response through the activation of ionotropic and metabotropic receptors.** (A) Silhouettes of the four phases of the C. elegans anterior touch escape response. Images were adapted from a movie of an animal executing an escape response. See text for details. (B) Schematic representation of the neural circuit that controls the C. elegans escape response. Synaptic connections (triangles) and gap junctions (bars) are as described by White et al. (1986) \\[20]. Green plus signs represent excitatory connections, and red minus signs indicate inhibitory connections. Sensory neurons are shown as triangles, command neurons required for locomotion are hexagons, and motor neurons are depicted as circles. The compass indicates anterior (A), posterior (P), ventral (V), and dorsal (D) directions. C. elegans sinusoidal locomotion is propagated by alternatively contracting and relaxing opposing ventral and dorsal body wall muscles of the animal using cholinergic (DB and VB for forward and DA and VA for backward locomotion) and GABAergic (VD and DD) motor neurons. Anterior touch induces the activation of the tyramine release from the RIM motor neurons (blue cells). Solid lines represent synaptic activation of LGC-55 in neurons and muscles (purple cells) that result in the inhibition of forward locomotion and suppression of head movement in the initial phase of the escape response. Dashed lines represent extrasynaptic activation of SER-2 in the GABAergic VD motor neurons (green cells). The activation of SER-2 causes a decrease in GABA release on the ventral side animal. This allows the hypercontraction of muscles on the ventral side of the animal, thus facilitating the execution of a ventral omega turn. doi:10.1371/journal.pbio.1001529.g007", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1814, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ccb8949e-f373-4218-b138-a47a3d6e2a44": {"__data__": {"id_": "ccb8949e-f373-4218-b138-a47a3d6e2a44", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.11, para 4](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "dff43153-e671-4f2c-bb68-b0253f796dd2", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.11, para 4](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "c99d568480844deeae606ed99b6a94e0fb4a5996004bc100ee9eb93e94b90d57", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|A|B|\n|-|-|\n|---|---|\n|touch|sensory input|\n|ALM|sensory neuron|\n|AVM||\n|forward|interneuron|\n|PVC||\n|AVD||\n|backward||\n|AVB|head motor neuron|\n|AVA||\n|LGC-55||\n|RMD|neck muscles|\n|RIM|head movements|\n|SMD||\n|SER-2||\n|DB|motor neuron|\n|VD||\n|DA||\n|VB|locomotion|\n|DD||\n|VA||\n|D||\n|A||\n|P||\n|V||\n|Tyraminergic neuron|gap junction|\n|LGC-55 expressing cells|chemical synapse|\n|SER-2 expressing cells||", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 398, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f5cbb124-50ce-4f56-b43a-1e5b2b68f152": {"__data__": {"id_": "f5cbb124-50ce-4f56-b43a-1e5b2b68f152", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.12, para 0](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "07717c15-e5ce-406c-bda3-905d419977dd", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.12, para 0](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "e4ddf55d2f4a24e2df309355684399163cfd4ffdf65c94e046395bdfd42efc7b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Monoaminergic Orchestration of a Complex Behavior", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 51, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "18ce0596-54dc-45df-a02a-7343c483f7c9": {"__data__": {"id_": "18ce0596-54dc-45df-a02a-7343c483f7c9", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.12, para 1](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c8ef2899-5718-4943-b6d0-8f4f36125d99", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.12, para 1](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "73b12d26ffe0c5a03119df663d80fd7d5b8eed88f65a738179967c5eed52180e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "were ablated initiated omega turns with a deep ventral head bend, but often their head failed to touch the ventral side of the body to close the omega turn (Figure S5). Animals with ablated GABAergic VD neurons did not have a defect in the execution of closed omega turns. The initiation of the omega turn may be triggered by the RIV head motorneurons that innervate ventral neck muscles \\[51]. The failure of DD ablated animals to fully close their omega turns indicates that the propagation of a sharp bend along the body requires the hypercontraction of ventral muscles and relaxation of dorsal muscles.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 606, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "67edcb6f-cb85-4d47-97b2-953960f4cada": {"__data__": {"id_": "67edcb6f-cb85-4d47-97b2-953960f4cada", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.12, para 2](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "63a7eb5f-5778-4039-ac41-cebbd9609530", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.12, para 2](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "db7d23c730d9793d728e8a8ce48036f4c61c28da4881d80beb63b04d2f5bd0ef", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Tyramine-deficient *tdc-1* mutants or RIM ablated fail to suppress head movements, make short reversals, and less frequently engage in the execution of omega turns \\[13,51]. In contrast, in response to anterior touch, *ser-2* mutants suppressed head movements and reversed similar to wild-type animals (Figure S6). Furthermore, *ser-2* mutants initiated an omega turn with a steep ventral head bend at the same frequency as the wild-type (Figure 6A). However, once *ser-2* mutants initiated the omega turn, the ventral turn was less deep than the wild-type. Whereas most wild-type animals\u2019 heads touched the ventral side of the body (86% \u00b1 3.6%, *n* = 51) during an omega turn, *ser-2* mutant animals failed to fully close the omega turn (27% \u00b1 7.8%, *n* = 62) (Figure 6B,C and Movies S4 and S5). Like the *ser-2* mutants, *tdc-1* mutants that are unable to synthesize tyramine and octopamine \\[13] failed to fully close the omega turn during the escape response (*tdc-1* 32% \u00b1 5.5%, *n* = 144). In contrast, *tbh-1* mutants, which only lack octopamine, executed closed omega turns (*tbh-1* 72% \u00b1 7.9%, *n* = 153), comparable to the wild-type. We measured the angle of the omega turn (omega angle) from the deepest most contracted region of the body to the closest or touching points in the head and tail (Figure 6B,D). Wild-type animals typically fully closed their omega bend, while *ser-2* mutants often failed to close omega bends, averaging an omega angle of 24\u00b0 \u00b1 2.3\u00b0 (*n* = 62). Animals lacking tyramine and octopamine (*tdc-1*) averaged an omega angle of 25\u00b0 \u00b1 3.6\u00b0, while animals lacking octopamine (*tbh-1*) alone closed their omega turn. Since touch stimuli in these assays have some inherent variability, we also induced reversals by optogenetic activation of the touch sensory neurons. Light induces an escape response in *Pmec-4::ChR2* transgenic animals that express the ChR2 in the touch sensory neurons \\[47,49,53]. We analyzed omega turns of *Pmec-4::ChR2* transgenic animals in response to blue light in both wild-type and *ser-2* mutant backgrounds. The light-induced escape response of *ser-2* mutants showed a similar defect in omega turns as with reversals induced by touch and had a lower frequency of closed omega turns than the wild-type (Figure 6C,D). The turning defects of *ser-2* mutants caused an alteration in the direction of reinitiated forward movement, or escape angle. In response to touch, wild-type animals and *tbh-1* mutants completely reversed their direction of locomotion with an escape angle of 179\u00b0 \u00b1 5\u00b0 (*n* = 42) and 177\u00b0 \u00b1 11\u00b0 (*n* = 16), respectively. In contrast, in response to touch, *ser-2* mutants and *tdc-1* mutants made a more shallow escape angle, changing their direction from the point of stimulus by 150\u00b0 \u00b1 5\u00b0 (*n* = 46) and 143\u00b0 \u00b1 6\u00b0 (*n* = 35) (Figure 6E,F). Genomic rescue lines partially restore the omega angle defect of the mutants and restored the escape angle to wild-type levels. Our data indicate that tyraminergic activation of SER-2 facilitates the execution of a tight ventral bend in the escape.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 3072, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1fba0fa7-e6f8-47a0-a787-ab65630caad0": {"__data__": {"id_": "1fba0fa7-e6f8-47a0-a787-ab65630caad0", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.12, para 3](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3b0043d4-0886-4860-a351-b99b797bbe3e", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.12, para 3](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "1a883c86d25d97fbaa0909df57efc34e1241593f41d886743c0cd77e4bd58feb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Discussion", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 13, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8418b005-ebac-40b8-a7a4-8481086ee69a": {"__data__": {"id_": "8418b005-ebac-40b8-a7a4-8481086ee69a", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.12, para 4](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ff208e7e-6822-49e7-9c3d-bcd035e119b5", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.12, para 4](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "9c4f3bd0aad0685920db8d62488e014c4a6d63f3f04525f7da2b06b85d59a983", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The concept of monoaminergic coding of behaviors originated from work in crustaceans and insects where fully coordinated behavioral sequences can be elicited by the injections of specific monoamines into the nervous system \\[6,16,17]. However, understanding how sensory inputs recruit the action of monoamines and how changes in circuit properties affect behavior remains a tremendous challenge in the mammalian and even insect nervous systems. Tyramine release from a single pair of neurons, acting on few tyramine receptors in the *C. elegans* nervous system with single-cell resolution, provides unique insights into how monoamines orchestrate independent motor programs in a complex behavior. In this study we analyzed how the G-protein coupled receptor SER-2 modulates the output of a neural circuit in a compound motor sequence.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 834, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ca1bed67-4f3e-4c08-aaa6-1b4d404aef68": {"__data__": {"id_": "ca1bed67-4f3e-4c08-aaa6-1b4d404aef68", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.12, para 5](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c2c91a5d-983c-4f38-90de-caf52eee4dc3", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.12, para 5](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "19bb3fe3235f2d4597d61218e58cab1ff85ce43f298d18c53398f1e65f1bb5e8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Tyramine Inhibits GABA Release", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 34, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "16e2fe28-abf4-49ae-8c3a-9eba9e4955e7": {"__data__": {"id_": "16e2fe28-abf4-49ae-8c3a-9eba9e4955e7", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.12, para 6](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "95db27e0-5947-4829-a682-4e857c90e3d3", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.12, para 6](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "7cbb4a6ff44176152b4d816f2420c5cb1b06c9ab05e556335bd27366aadccf71", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Our genetic data suggest that the tyramine receptor SER-2 acts in a G\u03b1o (GOA-1) pathway. The G\u03b1o/GOA-1 is expressed in all *C. elegans* neurons where it antagonizes G\u03b1q/EGL-30 function in many behaviors including locomotion, egg laying, and pharyngeal pumping \\[54,55]. Dopaminergic and serotonergic G-protein coupled receptors are expressed in *C. elegans* ventral cord neurons and their hyperactivation with exogenous dopamine or serotonin can induce paralysis within minutes \\[56\u201359]. However, *ser-2* and other individual biogenic amine receptor mutants have no obvious locomotion defects. This indicates that G\u03b1o/GOA-1 and G\u03b1q/EGL-30 integrate monaminergic signals to modulate neurotransmitter release from the motor neurons to control locomotion (Figure 1B). Dopamine, serotonin, and tyramine may allow the animal to refine locomotory patterns during different behavioral states. G\u03b1o/GOA-1 activity is thought to reduce the abundance of the synaptic priming protein UNC-13 at the synapse in *C. elegans* ventral cord neurons \\[33]. Our data indicate that tyramine reduces GABA release from VD motor neurons in a SER-2-dependent manner to augment the reorientation component of the escape response. In this regard, SER-2 shares similarities with mammalian alpha(2)-adrenergic receptors that inhibit neurotransmitter release and cause vasoconstriction during a fight-or-flight response \\[4].", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1395, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b956d504-9e12-445e-9059-9524d3339336": {"__data__": {"id_": "b956d504-9e12-445e-9059-9524d3339336", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.12, para 7](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "09da0742-8012-47c5-a8eb-a7640662a061", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.12, para 7](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "23a2e3362b004b58889865f03819ff157ff03ede9cc2477cd5990e86fc8b4f13", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Tyramine Acts Through Synaptic Activation of Ionotropic Receptors and Extrasynaptic Activation of Metabotropic Receptors", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 124, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "65917512-c8aa-44e9-ab50-99e578fac527": {"__data__": {"id_": "65917512-c8aa-44e9-ab50-99e578fac527", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.12, para 8](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "0b6e16d9-e0c0-46ce-ba44-6a03b8f3ef9e", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.12, para 8](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "5393377d0419281be5a55887385d0ec8530f338e45616ae380fbb370622f489b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Tyramine can act as a classical neurotransmitter in *C. elegans* through the synaptic activation of the tyramine-gated chloride channel, LGC-55 \\[22,60]. While LGC-55 is predominantly expressed in cells that are directly synaptic to tyraminergic RIM neurons, SER-2-expressing cells do not receive direct RIM innervation, indicating that SER-2 activation occurs extrasynaptically \\[28,36]. In addition, ionotropic and metabotropic receptors have distinct ligand affinity and signaling kinetics. Ligand-gated ion channels like LGC-55 have a relatively low affinity for their ligand (Kd 0.1 to 1 mM) and affect postsynaptic potentials within milliseconds. This allows for fast localized signaling between neurons and their postsynaptic partners. In contrast, G-protein coupled receptors have a high affinity for their ligand (Kd 0.1\u20131 \u03bcM) and operate on timescales from seconds to minutes \\[61]. Synaptic spillover from the synaptic cleft and diffusion can activate these high affinity receptors that are distant from the release site. As tyramine is released from a single pair of head neurons that extend processes into the nerve ring, the activation of SER-2 in the GABAergic VD neurons depends upon the diffusion of tyramine through the pseudocoelomic space to reach the VD processes along the length of the body. *C. elegans* has two other G-protein coupled receptors, TYRA-2 and TYRA-3, in addition to SER-2 that bind tyramine with high affinity \\[26,27]. *tyra-2* and *tyra-3* are", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1484, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "66d4547b-6f6e-462b-b3df-8c42aae62dcf": {"__data__": {"id_": "66d4547b-6f6e-462b-b3df-8c42aae62dcf", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.13, para 0](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "223d68c9-0338-4c72-bd99-233fdd19772f", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.13, para 0](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "0529411d93e48771fd9dbca7ea89a706864210903159fb7439da9cd53d280711", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Monoaminergic Orchestration of a Complex Behavior", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 51, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "27cdea47-3d20-49db-bcf0-2518dd711403": {"__data__": {"id_": "27cdea47-3d20-49db-bcf0-2518dd711403", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.13, para 1](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "908dbaf0-fd08-4729-8465-9ece5feb2258", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.13, para 1](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "7f38d00151ef539d34735891967498d030925384b2b51d0217a2b68e74afeb87", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "not expressed in cells that receive direct synaptic inputs from the tyraminergic RIM neurons \\[62]. Furthermore, no tyramine or octopamine reuptake transporter has been identified in either *C. elegans* or *Drosophila*, which suggests that tyramine diffusion from the synaptic cleft is part of its mechanism of action. Serotonin, dopamine, and octopamine receptors are also expressed in many *C. elegans* cells that are not directly postsynaptic to the small number of monoaminergic neurons that release them \\[36,58]. Similarly, in humans the monoaminergic cells are grouped in relative small nuclei that can affect large areas of the CNS or the periphery that do not receive direct synaptic inputs. Thus, monoamines are not confined to the anatomical connectome and can reconfigure outputs to large neuronal ensembles \\[63].", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 826, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cbfe1d95-f552-43a4-a38e-7795e7efc94a": {"__data__": {"id_": "cbfe1d95-f552-43a4-a38e-7795e7efc94a", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.13, para 2](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8e10678f-11ba-4e31-8e84-a93e4b829741", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.13, para 2](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "3de13d280e914011956eb90baf8131165afa8d459c4fbbde7bd4709790920843", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Tyramine Temporally Coordinates Independent Motor Programs in a Complex Behavior", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 83, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d2a3d7a5-1393-4377-b33e-55cf1c15e4b2": {"__data__": {"id_": "d2a3d7a5-1393-4377-b33e-55cf1c15e4b2", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.13, para 3](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e90c0092-71b0-4293-8324-e2d460546399", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.13, para 3](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "093190d14de25f387c9bfa387ebedca96b909f1ddf02c52bbc4d38c6cecac419", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The translation of sensory input into goal-directed behaviors requires the temporal coordination of independent motor programs. In response to gentle touch to the head, *C. elegans* engages in a compound motor sequence that allows the animal to retreat and navigate away from a touch stimulus (Figure 7A). In the base state, (I) forward locomotion is accompanied by exploratory head movements in which the tip of the nose moves from side to side. Gentle touch to the head of *C. elegans* elicits an escape response where the animal reverses its direction of locomotion while suppressing its exploratory head movements (II). Classic laser ablation experiments by Chalfie et al. (1985) \\[19] complemented by the known neural wiring diagram support a model in which the touch sensory neurons (ALM/AVM) inhibit the forward locomotion \u201ccommand\u201d neurons (PVC/AVB) and activate the backward locomotion \u201ccommand\u201d neurons (AVD/AVA), causing the animal to move backward away from the stimulus (Figure 7B). The AVA backward locomotion \u201ccommand\u201d neurons activate the electrically coupled tyraminergic RIM motor neurons, which exhibit coactivated calcium transients with the AVA \\[64,65]. Tyramine release from the RIM induces the suppression of head movements through the activation of the fast-acting inhibitory chloride channel, LGC-55, in neck muscles and cholinergic motor neurons that control head movements \\[13,22]. Activation of LGC-55 in the AVB forward locomotion \u201ccommand\u201d neurons further inhibits forward locomotion, stimulating long reversals that are coupled to the initiation of an omega turn \\[50,51]. The reversal is followed by a deep ventral head bend (III), allowing the animal to make a sharp (omega) turn (IV) where the head of the animal slides along the ventral side of the body and resumes forward locomotion (I). Our data show that extrasynaptic activation of the G-protein coupled tyramine receptor SER-2 contributes to the proper execution of the omega turn during the last stage of the escape response. The RIV and SMD head motor neurons have been implicated in the ventral head bend that initiates the omega turn \\[51]. *ser-2* mutants properly initiate the turn but bend less deep and the head often fails to touch the tail during the omega turn (IV).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2270, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e2813c17-308e-491a-bbaf-436165568f83": {"__data__": {"id_": "e2813c17-308e-491a-bbaf-436165568f83", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.13, para 4](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3b4539d4-97fa-4e55-b4f7-47019466e714", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.13, para 4](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "ea1b888c97209629f2124561cbc11e9c8d56a8e2d286b16dcc854ae0fd2299ec", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "*C. elegans* locomotion is controlled by cholinergic (A and B) and GABAergic (D) motor neurons that propel a wave of ventral-dorsal muscle flexures along the length of the body. We show that SER-2 inhibits neurotransmitter release from the GABAergic VD neurons. VD motor neurons release GABA on ventral body wall muscles and receive inputs from cholinergic DB neurons that synapse onto dorsal muscles. The DD motor neurons receive input from cholinergic VB motor neurons and release GABA on dorsal body wall muscles (Figure 4A) \\[20]. This organization indicates that GABAergic motor neurons are essential for contralateral muscle relaxation, thus promoting local bending during wave propagation \\[46].", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 702, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "33fe8e01-4c0b-4bae-b9ff-37d06e653954": {"__data__": {"id_": "33fe8e01-4c0b-4bae-b9ff-37d06e653954", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.13, para 5](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a860b5f7-f028-495f-b141-16af5a2813e7", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.13, para 5](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "c9506ad1dbc87034edc93d983e501ca05252c9833f92948c91f023f4811ec602", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "While spatial orientation in response to sensory stimuli is a fundamental component of animal behavior, the neural correlates are poorly understood. To change its direction of movement and navigate its environment, an animal needs to generate asymmetry in its locomotion pattern \\[66,67]. We show that the ablation of GABAergic VD neurons induces ventrally directed movement likely through the failure to properly relax the ventral muscles. Conversely, ablation of GABAergic DD neurons induces dorsally directed movement. Our experiments provide functional evidence that VD and DD neurons inhibit ventral and dorsal bending. Strikingly, the acute inhibition or activation of the DD motor neurons induces a sharp dorsal or ventral turn, respectively. Optogenetic neuronal stimulation can elicit distinct motor responses in multiple systems \\[47,68\u201370]. The optogenetic control of a single class of GABAergic neurons induces bi-directional steering and the remote control of animal navigation.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 991, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2fe02c3a-eb57-4214-b63c-f0e247f0be4e": {"__data__": {"id_": "2fe02c3a-eb57-4214-b63c-f0e247f0be4e", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.13, para 6](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fed34ba9-d893-47e2-9994-267d2d934336", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.13, para 6](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "f34c6b64a6bf08b6b28272f570afdfc1ba33a30da0e2e12949fb6069bd33cbea", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The ventral omega turn in the escape response occurs several seconds after the touch-induced reversal, which is within the time scale that GPCRs modulate neuronal activity. To make a tight turn the animal needs to generate an asymmetry in the excitation and inhibition of the ventral and dorsal muscle quadrants. Our data indicate that SER-2-mediated inhibition of GABAergic release onto the ventral muscles stimulates ventral muscle contraction and the proper propagation of the ventral body bend during the omega turn (Figure 7B). The kinetics of synaptic activation of the ion channel LGC-55 and extrasynaptic activation of the G-protein coupled receptor SER-2 temporally coordinates different phases of the escape response. Interestingly, the tyramine GPCR TYRA-3 modulates responses to pain-like stimuli and decision making \\[27,62]. This indicates that tyramine, much like the mammalian adrenergic signaling, coordinates different aspects of a flight response.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 966, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "72ede6a0-02c2-4ff0-965d-48be2180d83f": {"__data__": {"id_": "72ede6a0-02c2-4ff0-965d-48be2180d83f", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.13, para 7](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "daab672f-df5b-4f2b-ac39-a4baa4813e2f", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.13, para 7](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "896cc73d41a7ab8d0446d57fbbcedcfcce0774efe4ffe7acea42c9eb12f8614a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Our results provide molecular and neural insights on how monoamines reconfigure the output of neural circuits and orchestrate complex behaviors. Many neurotransmitters, including serotonin, GABA, acetylcholine, and glutamate, act through both ion channels and GPCRs in animals ranging from worms to man. We hypothesize that the temporally coordinated activation of ionotropic and metabotropic receptors may be a common signaling motif employed across organisms to orchestrate behavioral responses. Furthermore, the different monoamines appear to play a strikingly conserved role in the specification of distinct internal states, suggesting that the principles of neuronal modulation are conserved across species.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 712, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "50b7af74-872d-45d6-a921-2b277ec42169": {"__data__": {"id_": "50b7af74-872d-45d6-a921-2b277ec42169", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.13, para 8](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1fb56a1d-bca6-44b8-b15a-5229072a5494", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.13, para 8](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "8f9f3357b09bb2840a25dbfd87618d128b9f1902d4ee4f5076a387698fa36199", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Materials and Methods", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 24, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "038b4419-2e92-48e3-8455-41b9795aee1c": {"__data__": {"id_": "038b4419-2e92-48e3-8455-41b9795aee1c", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.13, para 9](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d2defdee-8897-431c-904b-15abf7597b01", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.13, para 9](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "d56b3e1fb96ee583187b49313bce7d45fc61db7c81107964d7fad146a493fb7c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "All *C. elegans* strains were grown at room temperature (22\u00b0C) on nematode growth media (NGM) agar plates with OP50 *E. coli* as a food source \\[71]. The wild-type strain used in this study was Bristol N2. G-protein coupled receptor and signaling component mutants used in this study were OH313: *ser-2(pk1357)*, QW329: *ser-2(ok2103)*, QW245: *lgc-55(tm2913)*, QW42: *tyra-2(tm1815)*, VC125: *tyra-3(ok325)*, JT734: *goa-1(sa734)*, JT748: *dgk-1(sa748)*, JT609: *eat-16(sa609)*, EG4532: *egl-30(tg26)*, CB156: *unc-25(e156)*, CB151: *unc-3(e151)*, QW284: *tdc-1(n3420)*, MT9455: *tbh-1(n3247)*, QW542: *unc-25(e156)*; *ser-2(pk1357)*, QW40: *lgc-55(n4331)*; *unc-3(e151)*, QW41: *ser-2(pk1357) unc-3(e151)*, QW837: *lgc-55(tm2913); ser-2(pk1357)*, and QW838: *lgc-55(tm2913); ser-2(pk1357) unc-3(e151)*. The rescue strains used were QW198: *Pser-2::SER-2::GFP, lin-15(+)*; *ser-2(pk1357) lin-15(n765ts)*, QW411: *Pser-2::SER-2::GFP, lin-15(+)*; *ser-2(pk1357) lin-15(n765ts)*, QW412: *Pser-2::SER-2::GFP, lin-15(+)*; *ser-2(pk1357) lin-15(n765ts)*, QW196:", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1056, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3b4f23d7-0f0e-4770-9486-84ce71f0a7a2": {"__data__": {"id_": "3b4f23d7-0f0e-4770-9486-84ce71f0a7a2", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.14, para 0](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "17377dff-5556-42f9-889f-a45d3f6a034b", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.14, para 0](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "4403f00630a50e2108a8f1583deb304a27e13d6930379e7fd9fa3f3c68f18f72", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Monoaminergic Orchestration of a Complex Behavior", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 51, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b9f80a2f-2be3-48db-8624-11ae4a8bffbf": {"__data__": {"id_": "b9f80a2f-2be3-48db-8624-11ae4a8bffbf", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.14, para 1](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "529e96f6-c93e-4106-8bf4-68785a575eca", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.14, para 1](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "63ddf9d8ec1aa2495381a45c1c92a811ad1cc78cad3bd312f40eb2b1393ba35f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Punc-47::SER-2, lin-15(+); ser-2(pk1357) lin-15(n765ts), QW897: \\[Punc-47::GOA-1::SL2::mCherry, unc-122::GFP] (zfEx347); goa-1(sa734), QW895: \\[Punc-47::EAT-16::SL2::mCherry, unc-122::GFP] (zfEx346); eat-16(sa609), and QW194: Pacr-2::SER-2, lin-15(+); ser-2(pk1357) lin-15(n765ts). The strains used for cell identification were EG1285: Punc-47::GFP(oxIs12), CX2835: Pglr-1::GFP(kyIs29), LX929: Punc-17::GFP(vsIs48), NY2037: Pflp-13::GFP(ynIs37), OH2246: Pser-2::GFP(otIs107), QW192: Pser-2::mCherry(zfIs8), QW122: Plgc-55::GFP(zfIs6), and QW84: Plgc-55::mCherry(zfIs4). The strains used for electrophysiological analysis were IZ33: unc-29(x29); acr-16(ok789) and IZ598: unc-29(x29); acr-16(ok789); ser-2(pk1357). The strains used for optogenetic assays were QW410: Pmec-4::ChR2::YFP, lin-15(+); ser-2(pk1357), QW409: Pmec-4::ChR2::YFP, lin-15(+); ser-2(ok2103), and QW429: Pflp-13::ChR2::GFP; Pflp-13::NpHR::CFP, lin-15(+); lite-1(ce314).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 938, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0d596040-636b-449d-af20-d3ec0c4f8584": {"__data__": {"id_": "0d596040-636b-449d-af20-d3ec0c4f8584", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.14, para 2](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "98ea68d4-a9da-4b16-a15d-b8756e55b7d0", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.14, para 2](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "6c780aab6689c5b675e77c5a4e382d098231030832452ccc72aa8b282cafe686", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Transgenic strains were generated by microinjection of plasmid DNA into the germ line of lin-15(n765ts) mutants with the pL15EK rescuing plasmid. Extrachromosomal arrays were integrated by X-ray irradiation (120 kV) and resulting transgenic strains were outcrossed at least four times to N2. A Pser-2::SER-2::GFP rescue construct was made by cloning 10.2 kb of genomic sequence including 2.2 kb upstream of the first translational start site into the pPD95.70 vector. The genomic rescue constructs used for exogenous tyramine and omega turn assays were injected between 10 and 20 ng/\u03bcl. A Pser-2::mCherry mini-gene reporter was constructed by cloning an 11.8 kb sequence that included the three start sites, first intron, and part of exon 2 into the pDM1247 vector. The GABAergic and cholinergic cell-specific rescue lines were cloned using ser-2a cDNA behind the unc-47 (1.2 kb) \\[72] and acr-2 (3.4 kb) promoters, respectively \\[73].", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 935, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f0a7be44-a70d-470a-bb67-c8a7372a78a0": {"__data__": {"id_": "f0a7be44-a70d-470a-bb67-c8a7372a78a0", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.14, para 3](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1a04469a-cb27-4823-8c2b-cb82b7353005", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.14, para 3](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "f05023c28960cce9f3915f00fc04cf92915907e65dc63bf5bb28eefe70f27436", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "A Pmec-4::ChR2::YFP plasmid \\[47] was injected at 80 ng/\u03bcl. The integrated strain was crossed into two ser-2 mutant allele backgrounds. Pflp-13::ChR2::GFP; Pflp-13::NpHR::CFP was cloned by inserting a 2 kb promoter from Pflp-13::GFP \\[37] into ChR2 and NpHR vectors \\[47,48]. The integrated strains carrying ChR2 or NpHR transgenes were cultured on NGM agar plates containing OP50 E. coli supplemented with 1.3 mM all-trans-retinal for one generation. Larval L4 animals were transferred to retinal plates 24 h before behavioral assays.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 535, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c3d480c3-5646-4a2d-88a1-70a9b9cbaa28": {"__data__": {"id_": "c3d480c3-5646-4a2d-88a1-70a9b9cbaa28", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.14, para 4](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b5511d85-771e-4866-ae4b-f485f6bbefba", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.14, para 4](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "c649eb85752288fc469c8ca170d32b43fcc388d40160682011633c409c449d44", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Ventral nerve cord expression analysis was performed using Pser-2::mCherry, Punc-47::GFP, and Punc-17::GFP transgenic animals. Head muscle analysis was done using Pser-2::GFP and Plgc-55::mCherry. Images were taken using confocal microscopy (Zeiss and Pascal imaging software) and formatted using ImageJ software.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 313, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1480671f-cc0c-47e8-9074-2d3c142f96c5": {"__data__": {"id_": "1480671f-cc0c-47e8-9074-2d3c142f96c5", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.14, para 5](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5e10a46b-406f-49ea-9d0f-751abd4ef0e9", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.14, para 5](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "6afb1e6e7814fe20f492323ccb60612fc5626fa52760596cfa0531c36e6e00a6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Behavioral Assays", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 20, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "79676535-0111-44eb-9b47-47c52d104b28": {"__data__": {"id_": "79676535-0111-44eb-9b47-47c52d104b28", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.14, para 6](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c853f91e-b6d7-4cba-9000-170647c0283a", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.14, para 6](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "76393dedceb2da8266919815c9242f50b2a33dad6fa7f9ab4891b0c24da192ff", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Behavioral assays were performed at room temperature. Drug assays were conducted on young adult animals aged 24 h post-L4 larval stage. Locomotion assays were performed on agar plates containing 2 mM acetic acid with or without tyramine hydrochloride (Sigma-Aldrich). Approximately 10 animals were transferred to assay plates and scored for locomotion every minute over a 20-minute period. Animals were scored as immobilized if there was no sustained forward or backward locomotion in a 5-s interval. Aldicarb drug assays were performed using NGM agar plates supplemented with 0.5 mM aldicarb (Sigma-Aldrich) with or without 30 mM tyramine. Locomotion is not obviously affected on plates with 30 mM tyramine dissolved in NGM agar instead of the agar used in exogenous tyramine paralysis assays. Animals were scored as paralyzed when they did not move when prodded with a platinum wire.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 885, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9463b964-68e6-46cf-a09b-22c20250958e": {"__data__": {"id_": "9463b964-68e6-46cf-a09b-22c20250958e", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.14, para 7](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "90c1867f-01b2-4b77-9417-f21ad4cfc039", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.14, para 7](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "8cc490f5283c30c1f1247e52c665e6c6fefc9db10857f33f64c7cd14a594f9f1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Optogenetic blue and green light-induced bending assays were performed with Pflp-13::ChR2::GFP; Pflp-13::NpHR::CFP; lite-1(ce314) transgenic animals. Bending behavior movies, worm tracking traces, and kymographs were generated using the CoLBeRT worm tracking system as previously described \\[49]. Animals were placed in between two glass slides in 200 \u03bcl of NGM containing 30% dextran. The space between the slides was approximately 0.127 mm and limited locomotion to two dimensions. The ventral nerve cord was illuminated with blue or green light using the micromirror control of the CoLBeRT system, and the behavior was analyzed using custom tracking software written in MATLAB. For assays used to calculate a bending index, young adult animals were transferred to NGM plates without food for 45 min. Food deprivation stimulated long forward runs, which facilitated the analysis of light-induced bending. Animals were exposed to blue or green light, using GFP (525 nm) and Rhodamine (550 nm) filters for 3 s. A dorsal or ventral bend were scored if the bend was larger than 45\u00b0. The bending index was calculated as the fraction of dorsally bending worms minus the fraction of ventrally bending worms. A positive fraction indicates a dorsal bias, a negative fraction indicates a ventral bias, and a zero value represents no directional bias or no response to light exposures.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1376, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5c88f3ca-d84a-4210-b553-133111cdc2c9": {"__data__": {"id_": "5c88f3ca-d84a-4210-b553-133111cdc2c9", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.14, para 8](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7a8c6435-d589-4883-95ba-266491637c07", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.14, para 8](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "459ce76863d6041fda4cd4e105f345fab9a4efdd5e3a9bf6b52012ace81bcece", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Omega turns were analyzed on NGM agar plates 2 d postpouring to control for assay plate humidity. Assay plates (60 mm diameter) were seeded with 40 \u03bcl OP50 E. coli and grown overnight at 37\u00b0C to produce a thin bacterial lawn. Young adult worms were transferred to an omega assay plate and allowed to acclimate for at least 10 min. Omega turns were induced by gentle anterior touch with fine eyebrow hair while recording using a FireWire camera and Astro IIDC software. For Pmec-4::ChR2::YFP-induced omega turns, animals were exposed to blue light for 5 s to induce a reversal. Bending angles and locomotion trajectories were calculated using Image J software analysis of movie stills. An omega turn was classified as a sharp turn larger than 90\u00b0 from the initial trajectory, following a reversal of three or more body bends. The omega angle was measured using the deepest part of the bend as the apex with vectors extending to the closest points along the body. Angles larger than 60\u00b0 were not scored. The escape angle was measured as the angle between the reversal trajectory and the trajectory of reinitiation of forward locomotion after the omega turn.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1155, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "80107aa3-016a-4d3c-b88e-34707b176389": {"__data__": {"id_": "80107aa3-016a-4d3c-b88e-34707b176389", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.14, para 9](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8023efa1-6ea5-4231-afcf-d2a6747720ec", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.14, para 9](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "53b38115772d7d53dffe416eac2f6d5e98aabfb0a07288d77bfd2702d4acf7ac", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Laser Ablations", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 18, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "9da0fe13-2f49-416a-adc7-bf6540465341": {"__data__": {"id_": "9da0fe13-2f49-416a-adc7-bf6540465341", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.14, para 10](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4143b620-55f9-48ad-9670-b0de26b12084", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.14, para 10](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "a20b97b713f024770e32c5cce06d6b6eb967b3d94a6fc166025624135f9a02af", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Animals were mounted on agar pads and anesthetized with 20 mM sodium azide. Laser ablations were done using standard methods \\[74]. DD and VD motor neurons were identified in Pflp-13::GFP animals in the L2 larval stage and Pser-2::GFP animals in the L3\u2013L4 larval stage, respectively. Following a recovery period of 1 to 3 d postablation, locomotion and omega turn assays were conducted on young adult animals. Locomotion patterns of animals that exhibited coordinated long runs were recorded at 7.5 fps. Movie analysis was done using MATLAB and the MATLAB Image Acquisition Toolbox \\[75]. To determine directionality for each locomotion trace, the slope of instantaneous direction over time was measured for individual 360 degree turning events. Laser ablation of motor neurons was confirmed by lack of GFP expression in the cell body positions in adult animals following behavioral experiments.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 895, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ae57b6cd-a61d-45f7-adaa-b86fa2b36e9e": {"__data__": {"id_": "ae57b6cd-a61d-45f7-adaa-b86fa2b36e9e", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.14, para 11](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6f0f2c50-02ce-4da9-9e2d-3e346d773c5a", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.14, para 11](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "8465b7f34f967154a36f03f79b7d826207bdf2668c50f6bdee63a94949a87941", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Electrophysiology", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 20, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c58ac31c-57d3-4e16-bcb2-4e4ee2c5af12": {"__data__": {"id_": "c58ac31c-57d3-4e16-bcb2-4e4ee2c5af12", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.14, para 12](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2ae2873c-e629-445e-84c1-82aac34d688d", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.14, para 12](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "e2951cc17b4748690d77a69bcbb54a0c1ee8a2a413657d1608580bf5a259c11a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Endogenous postsynaptic currents were recorded from body wall muscles as previously described \\[43]. All electrophysiology experiments were carried out at room temperature. Adult animals", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 186, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a1b9555f-2d0a-4187-b065-7c051105f4a1": {"__data__": {"id_": "a1b9555f-2d0a-4187-b065-7c051105f4a1", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.15, para 1](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8de7164f-c1d4-465b-84f4-ddb25ae55b1a", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.15, para 1](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "8be2501a1fb04865708092c50a8ba1ae13267750b2017e225b8645f8cbdb2f7a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "held at drop of bath solution were glued down to the sylgard\ncoated glass coverslip with cyanoacrylate tissue adhesive (Skin-\nstitch Corp.) applied along the dorsal side of the body. A\nlongitudinal incision was made by sharp glass electrode tip in the\ndorsolateral area, the intestine and gonad were removed, and the\ncuticle flap along the incision was glued down in order to expose\nthe ventral medial body wall muscles along the ventral nerve cord.\nThe preparation was then washed briefly for \\~20 s with a solution\nof collagenase type IV from Clostridium hystolyticum (Sigma-\nAldrich) in extracellular bath solution (at a concentration of 1 mg/\nml) in order to remove the basement membrane overlying the\nmuscles.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 714, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4cd6bf57-fed7-4fe9-b500-1865414ba29c": {"__data__": {"id_": "4cd6bf57-fed7-4fe9-b500-1865414ba29c", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.15, para 2](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e9cda2cf-9b35-46c6-897b-4dc09f81ac96", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.15, para 2](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "23f38263ad6c455aa18f7ded1cfdf1b90a33d5ebe5a535e038ba323002eb45c5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The extracellular solution consisted of 150 mM NaCl, 5 mM\nKCl, 4 mM MgCl2, 1 mM CaCl2, 15 mM HEPES, and 10 mM\nglucose (pH 7.4, osmolarity adjusted with 20 mM sucrose). The\nintracellular fluid (ICF) consisted of 25 mM K-gluconate, 115 mM\nKCl, 0.1 mM CaCl2, 50 mM HEPES, 5 mM Mg-ATP, 0.5 mM\nNa-GTP, 0.5 mM cGMP, 0.5 mM cAMP, and 1 mM BAPTA\n(pH 7.4, osmolarity adjusted with 10 mM sucrose). Whole-cell\nvoltage clamp recordings from *C. elegans* body wall muscle cells\n(group of ventral medial muscles 9, 11, 13) from +/+ and *ser-2*\nmutant strains were performed as previously described \\[43] using\nan EPC-10 amplifier (HEKA). Data acquisition and voltage\nprotocols were controlled by HEKA Patchmaster software. Patch-\nclamp electrodes were pulled from borosilicate glass with filament\n(Sutter Instrument), fire-polished to a resistance of 4\u20136 M\u03a9, and\nfilled with an internal solution. 1 M KCl electrode with agarose\nbridge served as reference electrode. Leak currents and liquid\njunction potentials were not compensated, though pipette offset\nwas zeroed immediately before getting a gigaohm seal. The\nmembrane potential was clamped at \u201360 mV. Data were\ndigitized at 6.67 kHz and low pass filtered at 3.3 kHz. Membrane\ncapacitance and the series resistance (at least 20%, up to 60%)\nwere compensated, and only recordings in which the series\nresistance was stable throughout the course of the recording were\nincluded. Endogenous synaptic activity data were collected in\ncontinuous mode (saved as 30-s recording sweeps). Typically, 60\u2013\n90 s of control endogenous activity was recorded followed by a 90-\ns bath tyramine application (100 \u00b5M), and subsequent tyramine\nwash-out (occasional). The muscle preparation was continuously\nperfused by extracellular solution with or without tyramine by\ngravity-flow at a perfusion rate of 2 ml/min. Cells were excluded\nfrom analysis if a leak current >300 pA was observed. Only\nrecordings with series resistance Rs<15 M\u03a9 were included in the\nanalysis. Data analysis and graphing were performed using Excel\n(Microsoft), Igor Pro (WaveMetrics Inc.), and GraphPrism\n(GraphPad Software). Mini Analysis software (Synaptosoft Inc.)\nwas used to detect and analyze the endogenous events off-line.\nParameters for detection of events were set as follows: amplitude\nthreshold 12 pA, period to search local minimum 80 ms, time\nbefore a peak for baseline 20 ms, period to search a decay time\n30 ms, fraction of peak to find a decay time 0.37, period to\naverage a baseline 10 ms, area threshold 10, and number of points\nto average for peak 3. In addition, following automatic detection of\nendogenous postsynaptic currents, traces were visually inspected,\nand all events were manually verified and accepted/rejected or\nrecalculated, if necessary. Sixty seconds of continuous data were\nused in analysis. Segments of 60-s recording prior to tyramine\napplication served as a control. The tyramine effect was evaluated\nin the last 60 s of a 90-s perfusion\u2014that is, initial 30 s of recording\nwith tyramine in bath solution were eliminated from analysis in\norder to allow enough time for adequate tyramine perfusion and\nstabilization effect. Data from each group were averaged, and\nstatistical significance between the strains was determined by two-\ntailed unpaired Student\u2019s *t* test. All chemicals were purchased from\nSigma-Aldrich.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 3346, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3ccacc3b-d81c-499e-ba7a-450be9c67e0e": {"__data__": {"id_": "3ccacc3b-d81c-499e-ba7a-450be9c67e0e", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.15, para 3](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8733145c-48e5-4fe0-8fb5-5c30d2976c5b", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.15, para 3](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "dcd034a820109d9e45ca4dc307d1a51564a2ef5a798f204b1853bceac648c1b3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Supporting Information", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 25, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "54a08e61-2854-47ae-8726-f8b0c936fe41": {"__data__": {"id_": "54a08e61-2854-47ae-8726-f8b0c936fe41", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.15, para 4](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d0fcdc85-d873-4491-a804-15dc1f9909bc", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.15, para 4](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "caed05de3cd67a40f0d6e18c4694e59f315b159de8beec3df7ad349bc050cceb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Figure S1** *C. elegans* become immobilized on exogenous tyramine\nin a dose-dependent manner. (A) Wild-type animals become\nimmobilized within 5 min on 30 mM tyramine (also see Pirri et\nal., 2009 \\[22]). (B) *ser-2* mutants are resistant to body immobiliza-\ntion compared to wild-type, but become immobilized by 60 mM\ntyramine. Each data point represents the mean \u00b1 SEM for at least\nfour trials totaling a minimum of 40 animals.\n(TIF)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 435, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "58ca428d-4a34-4fee-b971-9de86bb4c460": {"__data__": {"id_": "58ca428d-4a34-4fee-b971-9de86bb4c460", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.15, para 5](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f0380123-31dd-429b-92c9-6bcec0a10917", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.15, para 5](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "5f4ae9c1939607e41ab10eaff0ef3744abe06c34ff202de604ab47364200063e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Figure S2** *tyra-2* and *tyra-3* mutant animals paralyze on\nexogenous tyramine. (A) *tyra-2* and *tyra-3* mutants become\nimmobilized on plates containing 30 mM exogenous tyramine\nsimilar to wild-type. (B) Two additional SER-2 rescue strains\n(10 ng/\u00b5l injection) also rescue the immobilization resistance\nphenotype of *ser-2* mutants. Rescue denotes the transgenic line\n*Pser-2::SER-2; ser-2(pk1357)*. Each data point represents the mean\n\u00b1 SEM for at least five trials totaling a minimum of 50 animals.\n(TIF)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 510, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0b9f8589-bff8-4e91-ad35-4b08d5e1e532": {"__data__": {"id_": "0b9f8589-bff8-4e91-ad35-4b08d5e1e532", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.15, para 6](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "914500b9-ce3a-4505-8777-18743a466f69", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.15, para 6](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "d4f4772ed986a1bf97782e4466ef0114e6774a097b7d7a684ad3d00a0bce1675", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Figure S3** *Pser-2::GFP* and *Plgc-55::mCherry* are expressed in\ndifferent cells. (A\u2013C) Transgenic adult animal co-expressing (A)\n*Pser-2::GFP* and (B) *Plgc-55::mCherry*. (C) Merge. Head muscle\nexpression of *Pser-2::GFP* does not overlap with neck muscle\nexpression of *Plgc-55::mCherry*. Unlike *lgc-55* mutants, *ser-2*\nmutants do suppress head movements in response to touch. *ser-2*\nmutants occasionally reinitiate head movements before the\nreinitiation of forward locomotion (unpublished observation),\nwhich may suggest a role for *ser-2* in head muscles.\n(TIF)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 571, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "742f65bb-bcb1-46cc-96d8-5942bb7bfcb4": {"__data__": {"id_": "742f65bb-bcb1-46cc-96d8-5942bb7bfcb4", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.15, para 7](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a85fd827-0307-44f7-be24-74a604da5708", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.15, para 7](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "41d5ef11b2cb8ea53951a3c7f536463e6b96070236b526b798b7b702af8c6dd1", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Figure S4** SER-2 acts in a G\u03b1o pathway in GABAergic neurons.\n(A) Shown is the percentage of animals that display sustained\nlocomotion on 30 mM exogenous tyramine (see also Figure 2E).\n*unc-25* (GABA deficient) mutants and *unc-25; ser-2(pk1357)* double\nmutants are not resistant to the paralytic effects of exogenous\ntyramine. Expression of SER-2 in all GABAergic neurons (*Punc-\n47::SER-2*) restores sensitivity of *ser-2* mutants to exogenous\ntyramine. (B) Expression of GOA-1/G\u03b1o or EAT-16/RGS in all\nGABAergic neurons (*Punc-47::GOA-1* or *Punc-47::EAT-16*) partial-\nly restores sensitivity to exogenous tyramine in the respective *goa-1*\nand *eat-16* mutants. Each data point represents the mean percentage\nof animals immobilized by tyramine each minute for 20 min \u00b1\nSEM for at least three trials, totaling a minimum of 30 animals.\n(TIF)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 845, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "850d3838-ced3-4216-91d1-ee7851068a60": {"__data__": {"id_": "850d3838-ced3-4216-91d1-ee7851068a60", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.15, para 8](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7e5a825d-1d0a-4c35-bb3d-c0e69d71b430", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.15, para 8](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "f7f9c4f975650d19065e1e78175d8a64c654666eea7dff3d9d425db0b5c80975", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Figure S5** Ablation of GABAergic DD neurons impair ventral\nomega turns. Average number of closed omega turns made by\nanimals with either VD (*n* = 7) or DD (*n* = 12) neurons ablated or\nmock ablated animals (*n* = 13). Error bars represent SEM,\n\\*\\**p*<0.001, two-tailed Student\u2019s *t* test.\n(TIF)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 299, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "11a12581-27ff-4f8d-9226-c8b80307fd38": {"__data__": {"id_": "11a12581-27ff-4f8d-9226-c8b80307fd38", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.15, para 9](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1dd47002-6147-469e-b10d-3c5644756bae", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.15, para 9](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "d9ef16fd4fa11627e1f311a64f21cd29e99282465d56687741c6c4ca6f7f4739", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Figure S6** Reversal length after gentle anterior touch. Distribu-\ntion of the number of backward body bends in response to anterior\ntouch of wild-type and *ser-2* mutants. *n*\u2265250 animals per\ngenotype.\n(TIF)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 210, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8a2fbb08-6818-4d45-9dfe-4ed77be933af": {"__data__": {"id_": "8a2fbb08-6818-4d45-9dfe-4ed77be933af", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.15, para 10](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "59fc9da7-79fb-429d-a06c-0cb25d4b94ad", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.15, para 10](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "f75744c486fd24a32b6e6998f54cb71fb7de5651278fbf89932021e9fdeb5060", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Movie S1** Laser ablation of the DD GABAergic motor neurons\nresults in a dorsal bias during forward locomotion. The operated\nanimal locomotes in a circular pattern with its ventral side\n(location of the vulva) facing the outside of the circles.\n(MOV)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 252, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2ca6b54c-49b2-43c1-8a5f-f304847da2bd": {"__data__": {"id_": "2ca6b54c-49b2-43c1-8a5f-f304847da2bd", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.16, para 0](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "52ab44d0-e78f-4396-8cfb-8e30684b7cc0", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.16, para 0](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "360cc57f690b8c443bdd999a40d2d043d8475b7673b12a3d712ac5044b897f62", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Monoaminergic Orchestration of a Complex Behavior", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 51, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b4588ee4-59fa-495d-83b2-b97f558c2aac": {"__data__": {"id_": "b4588ee4-59fa-495d-83b2-b97f558c2aac", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.16, para 1](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6881a5b7-d766-4804-82a7-1dba2154e002", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.16, para 1](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "d058967cc26bbc09dd01658b31fd47dcef6c95b9e1fd26bad844de76544f99e7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Movie S2", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 11, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "dc4be705-b6fe-4418-9a1e-9f591009aeba": {"__data__": {"id_": "dc4be705-b6fe-4418-9a1e-9f591009aeba", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.16, para 2](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9037c3cf-424d-4069-bd24-f41ef3728872", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.16, para 2](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "0b32010d7385bf8c22e283d9080112936c413212fb77c5a8250212b3e183b2cd", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Laser ablation of the VD GABAergic motor neurons results in a ventral bias during forward locomotion. The operated animal locomotes in a circular pattern with its ventral side (location of the vulva) facing the inside of the circles. (MOV)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 239, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a12a6d78-e54b-4157-a33b-2677b1be5dc7": {"__data__": {"id_": "a12a6d78-e54b-4157-a33b-2677b1be5dc7", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.16, para 3](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7289c341-5525-4353-9796-ec67f309aae2", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.16, para 3](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "efe97b3812f8149d76f640a177fb7bdb9c4839dcf64159d2cd4d1cf42bd354d6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Movie S3", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 11, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "aee45397-041a-4847-ade1-d3074e5c3fd0": {"__data__": {"id_": "aee45397-041a-4847-ade1-d3074e5c3fd0", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.16, para 4](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "09c7f9ae-8b6d-4eb4-a8de-efff4e4b0a60", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.16, para 4](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "1471c87d3f9cc2bdd372657b4e892480431eeaf6f131d6e5682318382fba3912", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Tracking of a \\[Pflp-13::ChR2; Pflp-13::NpHR] single worm\u2019s locomotion and spatial illumination of the ventral nerve cord using the CoLBeRT system \\[49]. Inhibition of the DD motor neurons with green light activation of NpHR causes a dorsal bend. Activation of the DD motor neurons with blue light activation of ChR2 causes a ventral bend. (MOV)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 345, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "72f9de0c-3bd8-41bc-8f88-e1f3cabcfcd9": {"__data__": {"id_": "72f9de0c-3bd8-41bc-8f88-e1f3cabcfcd9", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.16, para 5](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8357f567-fbd1-4179-bded-7bb2c463e65b", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.16, para 5](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "0065d5842e1467e9f0096587e00e9bd95fcd94a480435984381fb7bb77599d98", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Movie S4", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 11, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e44000e4-b909-416a-aa02-9b0a244e4d1e": {"__data__": {"id_": "e44000e4-b909-416a-aa02-9b0a244e4d1e", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.16, para 6](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ca184df1-4dbe-473c-b78a-b34c78fcc774", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.16, para 6](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "8f7521c93a16b04e6106264d9af509b7d57bce33c6be030e3f1ed872f0cc6c21", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "A wild-type animal executing a complete omega turn in response to an anterior touch. Following a long reversal, the animal makes a deep ventral turn where the head of the animal touches and slides along the ventral side of the body and resumes forward locomotion in the direction opposite its original trajectory. (MOV)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 319, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "79cb1936-5688-4005-9480-15c11b1004e4": {"__data__": {"id_": "79cb1936-5688-4005-9480-15c11b1004e4", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.16, para 7](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "dc5103b6-a814-41c8-a3fe-5384ce608bdc", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.16, para 7](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "a141ec015acf625e034a01a009d7eaae0114b61b0ee0ae524a4df22ccb9499f0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Movie S5", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 11, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3a0435c3-6463-4f53-8652-59d4e8adea06": {"__data__": {"id_": "3a0435c3-6463-4f53-8652-59d4e8adea06", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.16, para 8](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3ab17508-f697-454b-a7da-4e3f3a8aca2f", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.16, para 8](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "e5f1cc5193de60dadf02c54c3ae9adc340b2271e91369a7e7f2fac8683b18fa7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "A *ser-2* mutant animal does not execute a complete omega turn in response to an anterior touch. Following a long reversal, the animal\u2019s head fails to touch the ventral side of the body. (MOV)", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 192, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "99b0493e-4fa5-4898-bc29-0192b19a36c6": {"__data__": {"id_": "99b0493e-4fa5-4898-bc29-0192b19a36c6", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.16, para 9](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "114bef96-e7c1-4962-847c-21ebb1579385", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.16, para 9](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "1f137789912501158c902ef7831fffb7bbf88e4fba2d403a2092417e24d09531", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Acknowledgments", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 18, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3e3f9815-da3b-4b7c-a33b-2879f41cd411": {"__data__": {"id_": "3e3f9815-da3b-4b7c-a33b-2879f41cd411", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.16, para 10](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6395d096-04f2-4bd6-abca-61a583f3dfd3", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.16, para 10](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "bf0bc7b2a86c90f30db930cfafff93fab34534283c802b0d6eaa318133799a76", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We thank the *Caenorhabditis* Genetics Center (CGC) for nematode strains; Andrew Fire, Chris Li, Michael Koelle, Alexander Gottschalk, and Yuji Kohara for reagents; and Claire B\u00e9nard and Scott Waddell for comments and helpful discussions.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 238, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "259ec4b5-45f5-44d7-ae02-b981b7f6c0a9": {"__data__": {"id_": "259ec4b5-45f5-44d7-ae02-b981b7f6c0a9", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.16, para 11](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "98fab202-424d-4008-8f7d-3bddfdfddd60", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.16, para 11](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "83abc0c74678f8aa06e488825a0c9cb0c9b6a203f9aeaff0ea6c70964c2627a7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Author Contributions", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 23, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "909ddafd-8ae0-4fad-b895-558251e22a27": {"__data__": {"id_": "909ddafd-8ae0-4fad-b895-558251e22a27", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.16, para 12](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2178a5de-d744-429b-baa1-7fbd2a8cd8fb", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.16, para 12](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "ab5f17111c55ba142593b029cc543f4a49ba8fcdcc191b995d3de576332c6d27", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The author(s) have made the following declarations about their contributions: Conceived and designed the experiments: JLD CMC AML JKP MMF ADTS MJA. Performed the experiments: JLD CMC AML JKP MH MMF MJA. Analyzed the data: JLD CMC AML JKP MH MMF ADTS MJA. Contributed reagents/materials/analysis tools: JLD CMC AML JKP MMF ADTS MJA. Wrote the paper: JLD CMC MMF MJA.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 365, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "84bcb0c8-264f-4eb4-a2e6-68e03d2c78d0": {"__data__": {"id_": "84bcb0c8-264f-4eb4-a2e6-68e03d2c78d0", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.16, para 13](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "54e5523f-edce-471b-9bdf-2608a8ec60c5", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.16, para 13](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "23eee5e935c06bce534d2ed1f41966518284b95f568a69d9f298bba2bc9a0219", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## References", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 13, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "78ef3e52-c532-423e-a1f8-297a8bcc584a": {"__data__": {"id_": "78ef3e52-c532-423e-a1f8-297a8bcc584a", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.16, para 14](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bfc75f24-a983-4f9d-b634-d83023d358f3", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.16, para 14](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "db3587ae70184fae2c2ef3d563a195f82816da9150e1411bc79ce4e149937d6a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "1. 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Curr Biol 13: 1317\u20131323.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 7052, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "439092e0-a466-4b95-9766-9931fb825726": {"__data__": {"id_": "439092e0-a466-4b95-9766-9931fb825726", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.17, para 0](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cf417a1f-0c22-4a3c-b505-6963a50414e4", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.17, para 0](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "a1f775c7c546284e7d63c88d45991d29b3f7f570357a73ff559da767406e1244", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# Monoaminergic Orchestration of a Complex Behavior", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 51, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fc8d2c51-39ac-4026-a0eb-9722176655e5": {"__data__": {"id_": "fc8d2c51-39ac-4026-a0eb-9722176655e5", "embedding": null, "metadata": {"source document": "Publication: [Donnelly2013, p.17, para 1](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "62319a9e-861a-4982-b99a-0458971a70ae", "node_type": "4", "metadata": {"source document": "Publication: [Donnelly2013, p.17, para 1](https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001529)"}, "hash": "e67ae0accc1abfba398bf8d4465ffc69b277101e87156241efa9f5d7adb221da", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "42. 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PLoS One 3: e2208. doi: 10.1371/journal.pone.0002208", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 5994, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cc660808-9fc9-4221-97c6-5393c3a6c1ce": {"__data__": {"id_": "cc660808-9fc9-4221-97c6-5393c3a6c1ce", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.1, para 0](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2f3f611c-bb24-4130-ada6-f4a5cbb153fb", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.1, para 0](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "c0255264221c51c34431a4beec5706fb7ad964590a7eb123f15ee5e00f9239cb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "TOXICOLOGICAL SCIENCES 106(1), 5\u201328 (2008)\ndoi:10.1093/toxsci/kfn121\nAdvance Access publication June 19, 2008", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 109, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c5aa2a40-a915-48ce-9bd1-26101b1a1acc": {"__data__": {"id_": "c5aa2a40-a915-48ce-9bd1-26101b1a1acc", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.1, para 1](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "35fb5441-7523-4408-b609-07009c2b4f07", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.1, para 1](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "4dcbcb74899b351e4f69c81d4db6214145fa79bf0dcee1ee963d0e2bdf28368d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# REVIEW", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 8, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ba9add90-f40f-4803-b448-41f3183cfa13": {"__data__": {"id_": "ba9add90-f40f-4803-b448-41f3183cfa13", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.1, para 2](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3e4cbbea-cce6-4bb9-85cf-39d71ca44caf", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.1, para 2](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "58a86ebc45580743b2f57104606901119b9b0cf9b66cc9749ef6acda71a01c1c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Caenorhabditis elegans: An Emerging Model in Biomedical and Environmental Toxicology", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 87, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d0bd6ba9-d291-4c2c-9fbe-9d41f0c05453": {"__data__": {"id_": "d0bd6ba9-d291-4c2c-9fbe-9d41f0c05453", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.1, para 3](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "987fc550-2914-4e78-9a70-f48cc7dca9d8", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.1, para 3](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "c28734a6388f21368016712322f61cc53224c91acf92088bae9bff1756a9e7d5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Maxwell C. K. Leung,\\* Phillip L. Williams,\u2020 Alexandre Benedetto,\u2021 Catherine Au,\u2021 Kirsten J. Helmcke,\u2021 Michael Aschner,\u2021 and Joel N. Meyer\\*^1", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 142, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "634220d7-4ca2-4b37-b7e8-90a11c3bf162": {"__data__": {"id_": "634220d7-4ca2-4b37-b7e8-90a11c3bf162", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.1, para 4](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "35ddf70f-232a-44cf-a04d-88f1f68af12a", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.1, para 4](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "3b67a72edec2b99547a9c46dfd3db81f2ff1a19da108a9b2daa043a1ddcb140e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "\\*Nicholas School of the Environment, Duke University, Durham, North Carolina 27750; \u2020Department of Environmental Health Science, College of Public University of Georgia, Athens, Georgia 30602; and \u2021Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee 37240", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 289, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "68965841-48e1-4e67-9ccc-a1100d95f7a2": {"__data__": {"id_": "68965841-48e1-4e67-9ccc-a1100d95f7a2", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.1, para 6](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "014009eb-3ef6-4c8e-9796-2b21be8bb235", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.1, para 6](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "4368002655200953cc3778adcb5d80dd905227a418c71c7afd2c1fe0ef5ebe8e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The nematode *Caenorhabditis elegans* has emerged as an important animal model in various fields including neurobiology, developmental biology, and genetics. Characteristics of this animal model that have contributed to its success include its genetic manipulability, invariant and fully described developmental program, well-characterized genome, ease of maintenance, short and prolific life cycle, and small body size. These same features have led to an increasing use of *C. elegans* in toxicology, both for mechanistic studies and high-throughput screening approaches. We describe some of the research that has been carried out in the areas of neurotoxicology, genetic toxicology, and environmental toxicology, as well as high-throughput experiments with *C. elegans* including genome-wide screening for molecular targets of toxicity and rapid toxicity assessment for new chemicals. We argue for an increased role for *C. elegans* in complementing other model systems in toxicological research.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 998, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6f5c36ea-4b7f-4065-926a-b688489303f3": {"__data__": {"id_": "6f5c36ea-4b7f-4065-926a-b688489303f3", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.1, para 7](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cb329a04-f0ee-43e6-bb60-5f6b361b7b95", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.1, para 7](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "93445d28acd09689a8c6578c2cb0d729de6782307fd422e5b131f6a3b98b378c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "**Key Words:** *Caenorhabditis elegans*; neurotoxicity; genotoxicity; environmental toxicology; high-throughput methods.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 120, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cae3c11e-42f4-4155-809a-d401f73ec340": {"__data__": {"id_": "cae3c11e-42f4-4155-809a-d401f73ec340", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.1, para 8](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f68f0a72-0a0d-4547-bc42-872071de5fdc", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.1, para 8](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "fadedceea781e4f7e9620189e448dd9a00b2eea03cb8d98ecaf168dbf6ad24d2", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "*Caenorhabditis elegans* is a saprophytic nematode species that has often been described as inhabiting soil and leaf-litter environments in many parts of the world (Hope, 1999); recent reports indicate that it is often carried by terrestrial gastropods and other small organisms in the soil habitat (Caswell-Chen *et al.*, 2005; Kiontke and Sudhaus, 2006). Although scientific reports on the species have appeared in the literature for more than 100 years (e.g., Maupus, 1900), the publication of Brenner\u2019s seminal genetics paper (Brenner, 1974) signaled its emergence as an important experimental model. Work with *C. elegans* has since led in a short time span to seminal discoveries in neuroscience, development, signal transduction, cell death, aging, and RNA interference (Antoshechkin and Sternberg, 2007). The success of *C. elegans* as a model has attracted increased attention as well in the fields of in biomedical and environmental toxicology.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 954, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "dce314de-a257-4768-8e92-ea6f328dba56": {"__data__": {"id_": "dce314de-a257-4768-8e92-ea6f328dba56", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.1, para 9](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c4b1b26d-6523-47a7-910e-3ea6e0436527", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.1, para 9](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "ef57a3538ecb7964a8cc06943b81407595669cf51a325f26d2f76d3322bf3437", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Clearly, *C. elegans* will be a valuable toxicity model only if its results were predictive of outcomes in higher eukaryotes. There is increasing evidence that this is the case both at the level of genetic and physiological similarity and at the level of actual toxicity data. Many of the basic physiological processes and stress responses that are observed in higher organisms (e.g., humans) are conserved in *C. elegans*. Depending on the bioinformatics approach used, *C. elegans* homologues have been identified for 60\u201380% of human genes (Kaletta and Hengartner, 2006), and 12 out of 17 known signal transduction pathways are conserved in *C. elegans* and human (NRC, 2000; Table 1). We discuss specific examples in the areas of neurotoxicology and genetic toxicology in this review.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 787, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2dc9f53f-69a0-48ca-9409-d704c2ab3a93": {"__data__": {"id_": "2dc9f53f-69a0-48ca-9409-d704c2ab3a93", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.1, para 10](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e579233b-d3e7-4ef9-984d-0a4d7d7c1ea4", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.1, para 10](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "e6f7440a6784ac927088c102ccff0963126e5d7d0e479c57da68048efa6e368a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "*Caenorhabditis elegans* has a number of features that make it not just relevant but quite powerful as a model for biological research. First of all, *C. elegans* is easy and inexpensive to maintain in laboratory conditions with a diet of *Escherichia coli*. The short, hermaphroditic life cycle (\\~3 days) and large number (300+) of offspring of *C. elegans* allows large-scale production of animals within a short period of time (Hope, 1999). Since *C. elegans* has a small body size, *in vivo* assays can be conducted in a 96-well microplate. The transparent body also allows clear observation of all cells in mature and developing animals. Furthermore, the intensively studied genome, complete cell lineage map, knockout (KO) mutant libraries, and established genetic methodologies including mutagenesis, transgenesis, and RNA interference (RNAi) provide a variety of options to manipulate and study *C. elegans* at the molecular level (Tables 2 and 3; for a more detailed presentation of genetic and genomic resources, see Antoshechkin and Sternberg, 2007). We address the particular power of these genetic and molecular tools in *C. elegans* at more length below.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1169, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3f216d9a-46d9-4c6d-a0ac-07e957998336": {"__data__": {"id_": "3f216d9a-46d9-4c6d-a0ac-07e957998336", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.1, para 11](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3a7001dd-8d52-49c4-abd3-acf8f5165712", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.1, para 11](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "50b1940c39debd99168a7836902efdb59bc54e0365919954cf37f43123df2e8e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Since reverse genetic and transgenic experiments are much easier and less expensive to conduct in *C. elegans* as compared", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 122, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ca34f465-b3b8-4898-9c15-fea4debd070a": {"__data__": {"id_": "ca34f465-b3b8-4898-9c15-fea4debd070a", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.1, para 12](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "67eb0d98-79d9-4f5c-9581-61e793ec3bbd", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.1, para 12](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "71a036500165c63a268ae430864c48f900b3f8ef856588c753cc3bfa9acc78b4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "^1To whom correspondence should be addressed at Nicholas School of the Environment, Box 90328, Duke University, Durham, NC 27708-0328. Fax: (919) 668-1799. E-mail:", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 163, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "59e6708b-1d68-4694-8d26-e26c22ab9ac5": {"__data__": {"id_": "59e6708b-1d68-4694-8d26-e26c22ab9ac5", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.1, para 13](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "91b52ba7-b79d-4513-b593-e2a08e2d3a1f", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.1, para 13](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "663a849877b359daf3598f2b30c4d6c09ae47e1cf78af441711ce50de3d8b1fb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ".", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7cc7268b-b973-493c-b739-f56ca964d1a7": {"__data__": {"id_": "7cc7268b-b973-493c-b739-f56ca964d1a7", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.1, para 14](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fe0eaeec-3eea-4c33-872d-1149d595c747", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.1, para 14](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "e0ba75abaf2ec747605e44eec536af3f08dcc0efde78433dddee9b8009c78acf", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "\u00a9 The Author 2008. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.\nFor permissions, please email:", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 147, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6ffc2ddd-8838-43ca-bd34-ff96575b965d": {"__data__": {"id_": "6ffc2ddd-8838-43ca-bd34-ff96575b965d", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.1, para 15](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "23b92f79-c205-4972-880a-5c8d9db2da9e", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.1, para 15](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "b24f69046e8e02bd21cb46a499343fe8784e8a5b5dd17bfcc5909d25c6559957", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ".\nThe online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 607, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6d937940-0cf4-4ab9-afbe-a50c26a997b6": {"__data__": {"id_": "6d937940-0cf4-4ab9-afbe-a50c26a997b6", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.1, para 16](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "909854d0-b870-42a0-af33-5a1460f97926", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.1, para 16](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "738c508c6d5712b20b0e1b6e87bffe65fb3c92ab5483ac59e1bf4d2f4b024066", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": ".", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b8f66386-f2c8-4412-a1d9-c86abcfc5a2b": {"__data__": {"id_": "b8f66386-f2c8-4412-a1d9-c86abcfc5a2b", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.2, para 0](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5092b10b-6e27-4825-9f97-da6865ee1568", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.2, para 0](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "655ec736789dbd819c3da94da8550996d0f289d322f7ecb39e5b2d639d4a18c8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "6                                                                              LEUNG ET AL.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 91, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "34cb778a-4bab-4cde-bef1-c7327a3c89bb": {"__data__": {"id_": "34cb778a-4bab-4cde-bef1-c7327a3c89bb", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.2, para 1](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6590ac96-8340-4380-85fe-dac0570fdd0a", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.2, para 1](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "a000e1b8d7e32a4fb9c88fc0f357434354ca4f5b6f214b98194a56d9958cfb51", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "```\n                                                       TABLE 1                             the study of a functional multicellular unit, such as a seroto-\n                               Signal Transduction Pathways Conserved in Nematodes and     nergic synapse, instead of a single cell (Kaletta and Hengartner,\n                               Vertebrates^a,b                                   2006). *Caenorhabditis elegans* also enables the detection of\n                                                                                           organism-level end points (e.g., feeding, reproduction, life\n```", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 614, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "79cae226-4974-43e8-837c-e3259931fa02": {"__data__": {"id_": "79cae226-4974-43e8-837c-e3259931fa02", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.2, para 2](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8aa5e495-5753-43cc-b2dd-9394abe08f34", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.2, para 2](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "6c0784dd3eae3781086fb1f37e663e28e3e9cba08f4fe8d8a9cf4199007916d4", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Pathways involved in early development                                                         span, and locomotion) and the interaction of a chemical with\nWnt pathway via \u03b2-catenin                                                                 multiple targets in an organism. Thus, *C. elegans* complements\nReceptor serine/threonine kinase (tumor growth factor-\u03b2 receptor) pathway                 both *in vitro* and *in vivo* mammalian models in toxicology.\nReceptor tyrosine kinase pathway (small G-protein \\[Ras] linked)                           Of note, these characteristics facilitate high-throughput experi-\nNotch-delta pathway\nReceptor-linked cytoplasmic tyrosine kinase (cytokine) pathway                            ments that can examine both fundamental toxicity, which are\nPathways involved in later development (e.g., organogenesis and tissue                         critical since so many chemicals have yet to be thoroughly tested,\nrenewal)                                                                                  and the gene-gene and gene-environment interactions whose\nApoptosis pathway (cell death pathway)                                                    importance is just beginning to be appreciated in toxicology.\nReceptor protein tyrosine phosphatase pathway                                             Here we review three major applications of *C. elegans* in\nPathways involved in the physiological function of differentiated cells of the\nfetus, juvenile, and adult                                                                biomedical and environmental toxicology: (1) mechanistic\nG-protein\u2013coupled receptor (large G-protein) pathway                                      toxicology, with a focus on neurotoxicity and genotoxicity; (2)\nIntegrin pathway                                                                          high-throughput screening capabilities; and (3) environmental\nCadherin pathway                                                                          toxicology and environmental assessment. We emphasize\nGap junction pathway                                                                      studies of neurotoxicity because they are the area of toxicology\nLigand-gated cation channel pathway\nin which *C. elegans* has been most exploited to date. We ^aAdapted from NRC (2000).                                                      discuss research methods, recent advances, and important ^bSignal transduction pathways that are not conserved in nematodes and                     considerations including limitations of the *C. elegans* model.\nvertebrates include the Wnt pathway via c-Jun N-terminal kinase, the\nHedgehog pathway (patched receptor protein), the nuclear factor kappa-B\npathway, the nuclear hormone receptor pathway, the receptor guanylate cyclase\npathway, and the nitric oxide receptor pathway.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2883, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fd6a472f-7ffc-48af-800a-5ba4608a7966": {"__data__": {"id_": "fd6a472f-7ffc-48af-800a-5ba4608a7966", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.2, para 3](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e5d7d71c-67c1-4fb1-9d48-611040e30cf1", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.2, para 3](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "39dc168dab2a2bba12e9de900bf30a55aa5d2d3549fc7e260ed9857d0af34821", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "to many other model systems, it is a useful model for molecular                                        Caenorhabditis elegans AND NEUROTOXICITY\nanalyses of the response of conserved pathways to *in vivo*                   Caenorhabditis elegans Is Well Suited for\nchemical exposure. As an *in vivo* model, *C. elegans* provides                                          Neurophysiology Analysis of Neurotoxicity\nseveral characteristics that complement *in vitro* or cellular                           With 302 neurons representing 118 characterized neuronal\nmodels. The use of whole-organism assays, first of all, allows                                  subtypes (Hobert, 2005), *C. elegans* provides an *in vivo* model", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 718, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "65cc412e-71e1-478a-862b-631ea643c6aa": {"__data__": {"id_": "65cc412e-71e1-478a-862b-631ea643c6aa", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.2, para 4](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e59eae0d-02c1-414f-a80b-f26fe8bd3a98", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.2, para 4](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "e4e30a4bf1becdbfa0cf2d3de74a2b18d39713bc89ce69e3be377e85dc3b0dde", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "```\n                                                                                                                        TABLE 2\n                                                                                    Examples of Mutational Analysis of *Caenorhabditis elegans* in Toxicology Research\n```", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 302, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3ee0b9f9-3927-4707-a49b-9ab1c4bd4038": {"__data__": {"id_": "3ee0b9f9-3927-4707-a49b-9ab1c4bd4038", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.2, para 5](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1a69f94c-cd10-4210-bb89-22b3089a1a42", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.2, para 5](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "b4b14c5ac3fc496c69c98eace848079a9d245adb7aa0db13d35ffd740984196e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Approach/toxin investigated|Mutants used|Major findings|References|\n|-|-|-|-|\n|\\*\\*A. KO mutant analysis\\*\\*||||\n|Black widow spider venom|\\*lat-1\\*: KO of latrophilin|Latrophilin is the receptor responsible for the toxicity of venom|Mee \\*et al.\\* (2004)|\n|As|\\*asna-1\\*: KO of ArsA ATPase|ArsA ATPase is important in Ar resistance in both bacteria and animals|Tseng \\*et al.\\* (2007)|\n|Cd|\\*pgp-5\\*: KO of a ABC transporter|ABC transporter is required for resistance to Cd toxicity|Kurz \\*et al.\\* (2007)|\n|PCB52|\\*cyp-35A1\\* to \\*cyp-35A5\\*: KOs of cytochrome P450 35A subfamily|CYP35A is required for fat storage and resistance to PCB52 toxicity|Menzel \\*et al.\\* (2007)|\n|\\*\\*B. Forward genetics screen\\*\\*||||\n|BPA|\\*bis-1\\*: mutant created from EMS mutagenesis|Collagen mutants are hypersensitive to BPA|Watanabe \\*et al.\\* (2005)|\n|Phosphine|\\*pre-1\\*, \\*pre-7\\*, \\*pre-33\\*: mutants created from EMS mutagenesis|Uptake and oxidization of phosphine are directly associated with oxidative stress in cells|Cheng \\*et al.\\* (2003)|\n|Bt toxins|\\*bre-1\\* to \\*bre-5\\*: mutants created from EMS mutagenesis|Five new genes involved in Bt toxicity are identified|Marroquin \\*et al.\\* (2000)|\n||\\*bre-5\\*: KO of \u03b2-1,3-galactosyltransferase|Carbohydrate modification is involved in Bt toxicity|Griffiths \\*et al.\\* (2001)|\n||\\*bre-2\\* to \\*bre-5\\*: KOs of glycolipid carbohydrate metabolism|Glycolipid receptors are targets of Bt toxins|Griffiths \\*et al.\\* (2005)|\n||\\*bre-1\\*: KO of GDP-mannose 4,6-dehydratase|The monosaccharide biosynthetic pathway is involved in Bt toxicity|Barrows \\*et al.\\* (2007b)|\nNote. ABC, ATP-binding cassette; PCB52, polychlorinated biphenyl 52; EMS, ethane methyl sulfonate.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1705, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8299031f-aa4f-427d-807d-7a1574633f8a": {"__data__": {"id_": "8299031f-aa4f-427d-807d-7a1574633f8a", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.3, para 1](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "32b2ea25-baef-4834-9fdb-370b40a7860d", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.3, para 1](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "0ef2f0d9b9d32ae5a5982b55597116a42b8878e5e2272bb80011c65ef1c0e69b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "TABLE 3\nExamples of Transgenic *Caenorhabditis elegans* Used in Toxicology Research", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 83, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "63bc490f-1c74-4cf4-b614-f25850857d6f": {"__data__": {"id_": "63bc490f-1c74-4cf4-b614-f25850857d6f", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.3, para 2](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "9a555554-5390-4020-95e1-a6093de6365f", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.3, para 2](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "1a503ac09fb4ca6afe2d8ee51d244357e1a2033b83ffda1df1f06903d6694c79", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Field/target tagged|Reporter used|Applications|References|\n|-|-|-|-|\n|\\*\\*A. Mechanistic studies\\*\\*||||\n|DAergic neurons|GFP|Detect neurodegradation caused by chemicals|Jiang \\*et al.\\* (2007)|\n|CYP14A3 and 35A3|GFP|Detect intestinal CYP overexpression in response to PCB52 as well as other xenobiotic CYP inducers|Menzel \\*et al.\\* (2007)|\n|GST|GFP|Measure GST induction in response to acrylamide as well as other inducers of oxidative stress|Hasegawa and van der Bliek (in press)|\n|\\*\\*B. Environmental biomonitoring\\*\\*||||\n|Heat shock proteins|GFP; \u03b2-galactosidase|Widely used for measuring stress response associated to toxicity of heavy metals, fungicides, pharmaceuticals, as well as field samples|Dengg and van Meel (2004); Easton \\*et al.\\* (2001); Mutwakil \\*et al.\\* (1997); Roh \\*et al.\\* (2006)|\n|Metallothionein|\u03b2-galactosidase|Specifically used for monitoring the bioavailability of heavy metals|Cioci \\*et al.\\* (2000)|\n|ATP level|Firefly luciferase|Measure the reduction of metabolic activity in response to environmental stressor|Lagido \\*et al.\\* 2001|\nNote. CYP, cytochrome P450; GST, glutathione S-transferase.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1133, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "97377652-68fb-4086-8475-675fd681f2ef": {"__data__": {"id_": "97377652-68fb-4086-8475-675fd681f2ef", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.3, para 3](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e327cc6f-189d-4f3f-8516-201c60a2e1e8", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.3, para 3](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "c4bcebad66c39b56e5d7369dddf172bcb2925c9ef39f28509bacfc11dbde660b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "for studying mechanisms of neuronal injury with resolution of single neurons. It initially underwent extensive development as a model organism in order to study the nervous system (Brenner, 1974), and its neuronal lineage and the complete wiring diagram of its nervous system are stereotyped and fully described (Sulston, 1983; Sulston *et al.*, 1983; White *et al.*, 1986). Each neuron has been assigned a code name corresponding to its location. For example, ADEL describes the dopaminergic (DAergic) head neuron \u201canterior deirid left.\u201d This relatively \u201csimple\u201d nervous system is comprised of 6393 chemical synapses, 890 electrical junctions, and 1410 neuromuscular junctions (Chen *et al.*, 2006). Additionally, the main neurotransmitter systems (cholinergic, \u03b3-aminobutyric acid (GABA)ergic, glutamatergic, DAergic, and serotoninergic) and their genetic networks (from neurotransmitter metabolism to vesicle cycling and synaptic transmission) are phylogenetically conserved from nematodes to vertebrates, which allows for findings from *C. elegans* to be extrapolated and further confirmed in vertebrate systems.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1116, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2781693b-f7f9-4652-8b21-f9e5c738ae63": {"__data__": {"id_": "2781693b-f7f9-4652-8b21-f9e5c738ae63", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.3, para 4](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "26ba5774-11d8-4296-ba08-eba8998c6131", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.3, para 4](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "344e42f48c9ec97f94e2e1a2deaa00a274d8787db1d40fea06a284cfc374afe6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Several genes involved in neurotransmission were originally identified in *C. elegans*. This is exemplified by the GABA vesicular transporter *unc-47* and the regulatory transcription factor *unc-30* (for review on the GABAergic system \\[Jorgensen, 2005]), the vesicular acetylcholine (ACh) transporter *unc-17* (for review on the cholinergic system \\[Rand, 2007]), the glutamate-gated chloride channel subunits \u03b11 and \u03b2 (*glc-1* and *glc-2*, respectively, for review on the glutamatergic system \\[Brockie and Maricq, 2006]), and the synaptic proteins *unc-18*, *unc-13*, *unc-26* (for review on synaptic function \\[Richmond, 2005]). Experiments challenging the *C. elegans* nervous system by laser ablation of individual neurons/axons, exposure to drugs, and other external stimuli have facilitated the design of robust behavioral tests to assess the function of defined neuronal populations (Avery and Horvitz, 1990; Bargmann, 2006; Barr and Garcia, 2006; Brockie and Maricq, 2006; Chase and Koelle, 2007; Goodman, 2006; Morgan *et al.*, 2007; Rand, 2007). For example, inhibitory GABAergic and excitatory cholinergic motor functions are assessed by quantifying the sinusoidal movement (amplitude and frequency of body bends) and foraging behavior of the worm. Motor and mechanosensory functions of glutamatergic neurons are evaluated by measuring the pharyngeal pumping rate and the response to touch. Mechanosensory functions of DAergic and serotoninergic neurons are appraised by observing the ability of worms to slow down when they encounter food. Furthermore, the creation of transgenic strains expressing fluorescent proteins in defined neurons allows *in vivo* imaging of any desired neuron. While experimentally challenging in the cells of microscopic animals, electrophysiology studies can be conducted with relative ease and success in live worms and cultured *C. elegans* neurons, establishing that they are electrophysiologically comparable to vertebrate neurons in their response to various drugs (Bianchi and Driscoll, 2006; Brockie and Maricq, 2006; Cook *et al.*, 2006; Schafer, 2006). Given the relative ease with which gene KO and transgenic animals can be generated, the ability to culture embryonic or primary *C. elegans* cells offers unique perspectives for neurotoxicology applications and study designs.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2330, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "537b5323-82be-44ad-afd2-74b96e1811e4": {"__data__": {"id_": "537b5323-82be-44ad-afd2-74b96e1811e4", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.3, para 5](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ac14a974-30b9-4997-8f9f-3aa1a0318f32", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.3, para 5](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "5c35bd94b20f858adfd7e0d764369b8f06f2a776b982f43bdd47f0bf449d8f41", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Caenorhabditis elegans Is a Potent Model to Decipher Genetic Aspects of Neurotoxicity", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 88, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "97c4b007-ab26-43ff-874b-04b9434388be": {"__data__": {"id_": "97c4b007-ab26-43ff-874b-04b9434388be", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.3, para 6](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cd715db9-f0d9-4384-9274-b502839d2aaf", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.3, para 6](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "5023f9bc86dfaedf634e0246a7ec960e1b9f7fc4c29f3da3175b705ec3b797f6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The conservation of neurophysiologic components from nematodes to humans largely relies on shared genetic networks and developmental programs. Hence, the availability of mutants for many of the *C. elegans* genes facilitated significant progress in unraveling of evolutionarily conserved cellular and genetic pathways responsible for neuron fate specificity", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 357, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "87f6584c-e2f4-4a1e-9d66-682ca774b0f2": {"__data__": {"id_": "87f6584c-e2f4-4a1e-9d66-682ca774b0f2", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.4, para 0](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d951f71f-4132-447f-8670-1f38a52d1348", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.4, para 0](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "8583bc4f630756ae6af4c224878f25331a3ab70788830c5650608c1977d690c8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "8                                                  LEUNG ET AL.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 63, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "66e2ca66-9a07-4004-a1f2-a2cab5c8191b": {"__data__": {"id_": "66e2ca66-9a07-4004-a1f2-a2cab5c8191b", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.4, para 1](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "72f7c253-1382-4f29-ba37-10348b10f3b7", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.4, para 1](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "2b27e0814f8de98f7da4ffd2050b1af3a8e82cabc865b0cf9e019549fc849f3d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "(Hobert, 2005), differentiation (Chisholm and Jin, 2005), migration (Silhankova and Korswagen, 2007), axon guidance (Quinn and Wadsworth, 2006; Wadsworth, 2002), and synaptogenesis (Jin, 2002, 2005). Recently, laser axotomy in *C. elegans* has been successfully applied to identify axon regeneration mechanisms (Gabel et al., 2008; Wu et al., 2007), which are of utmost importance in developing treatments to reverse neurodegenerative processes and spinal cord injuries. Essential cell functions relevant to neurotoxicity studies are also conserved. This is best exemplified by the mechanistic elucidation of the apoptotic pathway in *C. elegans*, for which the 2002 Nobel Prize in Physiology or Medicine was awarded (Hengartner and Horvitz, 1994; Horvitz, 2003; Sulston, 2003). The pathway is of direct interest to neurotoxicologists since apoptosis is implicated in many neurodegenerative diseases and toxicant-induced cell demise (Bharathi et al., 2006; Hirata, 2002; Koh, 2001; Mattson, 2000; Ong and Farooqui, 2005; Savory et al., 2003). Pathways relevant to oxidative stress\u2013related neuronal injuries, such as the p38 mitogen-activated protein kinase and AKT signaling cascades, the ubiquitin-proteasome pathway, and the oxidative stress response are also conserved in the worm (Ayyadevara et al., 2005, 2008; Daitoku and Fukamizu, 2007; Gami et al., 2006; Grad and Lemire, 2004; Inoue et al., 2005; Kipreos, 2005; Leiers et al., 2003; Tullet et al., 2008; Wang et al., 2007a).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1483, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4baa7e1a-46df-48bc-813d-6587c4b2609d": {"__data__": {"id_": "4baa7e1a-46df-48bc-813d-6587c4b2609d", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.4, para 2](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "531ad58a-717e-4893-b78f-09282604b932", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.4, para 2](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "e6664631ed3e72e86d44fb91e1bf516068a0417035c8e0501fb8b4acf4c0bffe", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The nematode model is also amenable to interesting genetic alterations. Hence, it is very easy to generate transgenic worms expressing any kind of mutant recombinant protein, providing means for the study of neurodegenerative diseases (see additional discussion below). Gene KO and altered function mutations are in many cases available from the Gene Knockout Consortium or the National BioResource Project of Japan (currently \\~1/3 of the \\~20,000 total genes in *C. elegans*; Antoshechkin and Sternberg, 2007) or alternatively are conveniently generated using chemicals, radiations, or transposons (discussed below under *Caenorhabditis elegans* and Genotoxicity). Hence, classical approaches to elucidate intracellular pathways in *C. elegans* include forward and modifier screens following random mutagenesis (Inoue and Thomas, 2000; Malone and Thomas, 1994; Morck et al., 2003; Nass et al., 2005; O\u2019Connell et al., 1998). Finally *C. elegans* is amenable to gender manipulation (possible generation of males, feminized males, masculinized hermaphrodites, or feminized hermaphrodites) permitting studies on sex specificity mechanisms of neurotoxicants or disorders and \u201crejuvenation\u201d by forcing development through the quiescent dauer larval stage (Houthoofd et al., 2002).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1277, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "afce41ab-d916-48c4-863b-f3d7228de128": {"__data__": {"id_": "afce41ab-d916-48c4-863b-f3d7228de128", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.4, para 3](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "822d19b8-a3cf-4d5b-9954-936e7c69de8e", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.4, para 3](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "076b7b4735a0e56449fbb58f4243fe60c5e6c874845c388f3b529f899fd3d252", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Neurotoxicological Studies in *C. elegans*", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 45, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5db583a7-38c5-46eb-bebe-8134ef5e924f": {"__data__": {"id_": "5db583a7-38c5-46eb-bebe-8134ef5e924f", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.4, para 4](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6605d991-05c9-4d3d-8143-c47bdb002bcb", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.4, para 4](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "d2ceff27b147eafe5fd077127d41fe02484c6d1795a00a472a0fc44e60068b8b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Years before the latest technologic developments (RNAi and high-throughput techniques), *C. elegans* was used to study toxicity mechanisms of environmental factors affecting the nervous system. The following section provides a synopsis of the available literature on neurotoxicity-related issues addressed in *C. elegans*. It is not meant to be exhaustive but rather to illustrate typical studies that are amenable in the *C. elegans* platform. We highlight studies with exposure outcomes to various metals and pesticides, as well as general considerations on studies of neurodegenerative diseases. We emphasize the utility of *C. elegans* in addressing hypothesis-driven mechanisms of neurotoxicity and extrapolations to vertebrate systems.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 741, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "87af0e17-29cf-40a1-83ab-c52197956a85": {"__data__": {"id_": "87af0e17-29cf-40a1-83ab-c52197956a85", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.4, para 5](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ef61499b-d41e-4b03-9c6f-e2532e49f0ee", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.4, para 5](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "16502a7a77360f8cb8efbcb41904646ea98d5882254f8613f9abef5331d75d88", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Toxicity Mechanisms of Neurotoxic Metals in *C. elegans*", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 60, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "71068746-0291-4c36-8038-ff2463124115": {"__data__": {"id_": "71068746-0291-4c36-8038-ff2463124115", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.4, para 6](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "51168d10-50da-4542-9165-7496c0db3a31", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.4, para 6](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "10b0d1a0dc3bd73d86c117c132b0e93b1f668b196506f632f83cccc3c16b056b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "*Caenorhabditis elegans* has been used as a model system to elucidate the toxicity and toxicological mechanisms of various heavy metals, such as Aluminum (Al), Arsenic (As), Barium (Ba), Cadmium (Cd), Copper (Cu), Lead (Pb), Mercury (Hg), Uranium (U), and Zinc (Zn). In general, these studies focused on various toxic end points, such as lethality, reproduction, life span, and protein expression. Some focus has also been directed to the effects of these metals on the nervous system by assessing behavior, reporter expression and neuronal morphology. We provide here a few examples of these approaches.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 604, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "81fe8281-102e-46b9-aa9c-12b1804f9a7a": {"__data__": {"id_": "81fe8281-102e-46b9-aa9c-12b1804f9a7a", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.4, para 7](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e2542235-9872-4bdc-9f33-41197b16bd9c", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.4, para 7](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "e56a4703473d4aa4c72fa03c75adb3ca4a9fc8906a429e59ea82ed3bfba56cc9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Investigators have performed numerous studies to assess behavior-induced alterations following exposure of the worm to heavy metals. Depending on the end point assessed, neurotoxic effects on specific neuronal circuitries can be inferred.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 238, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "04c6c26b-9f64-4683-ae18-02cb4962de27": {"__data__": {"id_": "04c6c26b-9f64-4683-ae18-02cb4962de27", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.4, para 8](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "96dbd32c-b92a-46aa-9773-7190207824d9", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.4, para 8](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "8f32fc2ecc64607fc6a6eb1c336cbb3bd928b99721ad232ebbd9a43418c873dc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "For instance, a defect in locomotion reflects an impairment of the neuronal network formed by the interneurons AVA, AVB, AVD, and PVC providing input to the A- and B-type motor neurons (responsible for forward and backward movement) and the inhibitory D-type motor neurons involved in the coordination of movement (Riddle et al., 1997). By recording short videos and subsequently analyzing them using computer tracking software, it has been possible to quantify the overall movement of *C. elegans* (distance traveled, directional change, etc.), body bends and head thrashes, upon metal treatments, allowing to further correlate the data with damages to neuron circuitries. These computer tracking studies showed that worms displayed a dose-dependent decrease in locomotory movement upon exposure to Pb (Anderson et al., 2001, 2004; Johnson and Nelson, 1991) and Al (Anderson et al., 2004), while an increase in locomotion was observed upon exposure to low concentrations of Hg as compared with Cu (Williams and Dusenbery, 1988). Another study showed that exposure to Ba impaired both body bend and head thrashing rates in a dose-dependent manner (Wang et al., 2008), corroborating mammalian data on the effect of Ba on the nervous system attributed to its ability to block potassium channels (Johnson and Nelson, 1991).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1320, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "45214000-b21c-4437-b571-c87e690eb3b1": {"__data__": {"id_": "45214000-b21c-4437-b571-c87e690eb3b1", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.4, para 9](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7eccb5ce-dc34-470d-8414-b53196fd159b", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.4, para 9](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "0963e8d1004d8dcc9411b4f4de68b3e9a5ea8dab3511438c06e13e838cbbbbc8", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Feeding behavior has also been shown to be affected upon heavy metal exposure. Feeding requires a different neuronal circuitry including M3 (involved in pharyngeal relaxation), MC", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 179, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1be4f9a9-e98d-4b79-8933-8d6f655374be": {"__data__": {"id_": "1be4f9a9-e98d-4b79-8933-8d6f655374be", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.5, para 0](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d6463cc0-3297-45b1-9df4-a6bfc882c294", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.5, para 0](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "7046fdfcb450758b2b119b7e8eef1ad673db4f2bffc1d986c920bbaa1c91051f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "CAENORHABDITIS ELEGANS IN TOXICOLOGY RESEARCH                                                               9", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 109, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4483315c-b279-4c35-b994-f967c3282f91": {"__data__": {"id_": "4483315c-b279-4c35-b994-f967c3282f91", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.5, para 1](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "706a1e6b-322a-40b7-a3d3-91f43d2f19e1", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.5, para 1](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "56488cddccd7a22e29c5cbb05c3148efb0016f8c20a6b542644e3af1bdb1335a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "(control of pumping rate), M4 (control of isthmus peristalsis), NSM (stimulate feeding), RIP, and I neurons (Riddle et al., 1997). A decrease in feeding was observed when worms were exposed to Cd or Hg (Boyd et al., 2003; Jones and Candido, 1999).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 247, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8e1a083f-5b72-4e56-bcc8-c8db24d16145": {"__data__": {"id_": "8e1a083f-5b72-4e56-bcc8-c8db24d16145", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.5, para 2](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a28b6a72-2f7d-4fc3-979e-cce911c91310", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.5, para 2](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "2a8dc8b189fdfda7f3605c3d19c8dae00028553576a63d19ebd1afe7b1a0436d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Behavioral research studying the effect of heavy metals on *C. elegans* has also taken the route of assessing the ability of the worm to sense the toxin and alter its behavior accordingly, involving other neural circuitry, such as the amphid and phasmid neurons responsible for chemosensation (Riddle et al., 1997). By generating concentration gradient\u2013containing plates, Sambongi et al. (1999) discovered that *C. elegans* was able to avoid Cd and Cu but not Ni and that the amphid ADL, ASE, and ASH neurons were responsible for this avoidance as their combined ablation eliminated the avoidance phenotype. Furthering the investigation into the role of ASH neurons, researchers found that a calcium (Ca^2+) influx could be elicited upon exposing the *C. elegans* to Cu, which may provide insight into the mechanism of the ability of the worm to display avoidance behaviors (Hilliard et al., 2005).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 898, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "eb236014-b60f-4af1-8311-c9af69da69ce": {"__data__": {"id_": "eb236014-b60f-4af1-8311-c9af69da69ce", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.5, para 3](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d807a2b4-859e-41f7-b54d-4374fe29d2df", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.5, para 3](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "a025cd7d3c4187977a27ba7a0dcf4e5b523f836ecd8ea25d1b1311c8a2c15784", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "*Caenorhabditis elegans* exhibits both short-term and long-term learning-related behaviors in response to specific sensory inputs (Rankin et al., 1990), which involve defined neuronal networks. As an example, thermosensation-associated learning and memory rely on the AFD sensory neuron sending inputs to the AIY and AIZ interneurons, whose signals are integrated by the RIA and RIB interneurons to command the RIM motor neuron (Mori et al., 2007). When assessing the function of this circuitry, worms grown and fed at a definite temperature are moved to a food-deprived test plate exposed to a temperature gradient. The ability of the worms to find and remain in the area of the test plate corresponding to the feeding temperature reflects the functioning of the thermosensation learning and memory network aforementioned (Mori et al., 2007). Interestingly, worms exposed to Al and Pb exhibit poor scores at this test, indicative of a significant reduction of the worms\u2019 learning ability (Ye et al., in press). This recapitulates the learning deficits observed in young patients overexposed to the same metals (Garza et al., 2006; Goncalves and Silva, 2007).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1159, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d5114d71-9d0f-47b4-a1ad-7ff5b88ed309": {"__data__": {"id_": "d5114d71-9d0f-47b4-a1ad-7ff5b88ed309", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.5, para 4](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e0c48026-9292-4293-838a-837e266690e9", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.5, para 4](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "fbf585935d3621537f465069ec52ca11c9be5d1db91618197c5dc2f767fd3f06", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "While behavioral testing was informative of the neuronal circuitries affected by heavy metals, additional experiments uncovered the molecular mechanisms of their neurotoxic effects. For example, in the previously described study, after determining that Al and Pb induced memory deficits, the investigators showed that the antioxidant vitamin E effectively reversed these deficits, indicating a role of oxidative stress in Al and Pb neurotoxicity (Ye et al., in press). The involvement of oxidative stress in metal-induced toxicity was further confirmed when worms mutated in glutamylcysteine synthetase (*gcs-1*), the rate-limiting enzyme in glutathione synthesis, exhibited hypersensitivity to As exposure when compared to wild-type animals (Liao and Yu, 2005).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 762, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f082c01d-e8b3-4113-8661-109eb4391c59": {"__data__": {"id_": "f082c01d-e8b3-4113-8661-109eb4391c59", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.5, para 5](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "599194ee-5757-4100-a50b-e77ca1642e34", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.5, para 5](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "76a3e9032bb1f36ae33ce091ecaf7b96ffa72bf36522bb8718033168b559c814", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Studies conducted in mammalian models found that Hg is able to block Ca^2+ channels. In neurons, this blockage can induce spontaneous release of neurotransmitters (Atchison, 2003). In *C. elegans*, the Ca^2+ channel blocker verapamil was found to protect against Hg exposure, suggesting that Ca^2+ signaling plays a role in the toxicity of Hg in this model organism as in mammals (Koselke et al., 2007).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 403, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "4e36e2d9-a54b-483e-a2f8-4eae89b388f4": {"__data__": {"id_": "4e36e2d9-a54b-483e-a2f8-4eae89b388f4", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.5, para 6](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2d345811-bf53-43e8-a77c-fec78f0ca64d", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.5, para 6](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "9d62f632314e6acaa878584d2c875228022ec98d2051ef7ab1fc2f7b3e0b007e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Observation of neuron morphology following heavy metal exposure was also performed using *C. elegans* strains expressing the green fluorescent protein (GFP) in discrete neuronal populations. Tests using depleted U evoked no alterations in the DAergic nervous system of *C. elegans*, an observation corroborated with data from mammalian primary neuronal cultures (Jiang et al., 2007). Meanwhile, *kel-8* and *numr-1*, which are involved in resistance to Cd toxicity, were upregulated upon Cd exposure. In particular, GFP levels of KEL-8::GFP and NUMR-1::GFP were increased in the pharynx and the intestine in addition to the constitutive expression observed in AWA neurons (Cui et al., 2007a; Freedman et al., 2006; Jackson et al., 2006; Tvermoes and Freedman, 2008). Furthermore, *numr-1* was shown to be induced in response to heavy metals, such as Cd, Cu, Cobalt (Co), Chromium (Cr), Ni, As, Zn, and Hg. NUMR-1::GFP was localized to nuclei within the intestine and the pharynx and colocalized with the stress-responsive heat-shock transcription factor HSF-1::mCherry (Tvermoes and Freedman, 2008). This indicates that these particular genes were altered in response to heavy metals and this may aid in the understanding of the toxicity of or the protection against these agents.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1280, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6f0f9df4-8429-4d22-a606-008e58de16cc": {"__data__": {"id_": "6f0f9df4-8429-4d22-a606-008e58de16cc", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.5, para 7](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ea6e839a-01a7-40da-a105-2f7ccef66e39", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.5, para 7](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "232d480a54087c234d619a95a1a3f4aae29a2641918420124910cb170a6d944c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Toxicity Mechanisms of Neurotoxic Pesticides in *C. elegans*", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 63, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fa536c30-692c-4155-8071-0b9519224290": {"__data__": {"id_": "fa536c30-692c-4155-8071-0b9519224290", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.5, para 8](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fc49693a-fdea-43ca-adb1-a7731152323f", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.5, para 8](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "b694858623756715c89414cbd832dce2dfc4ba8ca0799c8b0db2b9ea16b4e826", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Currently, there are over a hundred types of pesticides available and substantial efforts have been put forth to examine the neurotoxicity of these agents. Similarity in neural circuitry and the conservation in genetic makeup between *C. elegans* and humans have led to a number of recent studies on pesticide neurotoxicity in this species (summarized in Table 4). In this section, we discuss the effects of three groups of pesticides on neurological pathways in *C. elegans* and their relevance to understanding mechanisms of human neurotoxicity.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 547, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e20ed20e-baa3-457c-8e88-f403065a2fe8": {"__data__": {"id_": "e20ed20e-baa3-457c-8e88-f403065a2fe8", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.5, para 9](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4329f537-1667-41ee-9d3a-22dea0b8691a", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.5, para 9](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "8359b000a5545b2297f824c59d9dbbd2d3c99e1c6c59459be3664f7cea9638bb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Paraquat, also known as methyl viologen (mev), is mainly used as an herbicide. Increased concerns for the potential human risks associated with paraquat exposure stems from studies indicating that subjects experiencing exposure to this and other herbicides/insecticides have a higher prevalence of Parkinson disease (PD) (Liou et al., 1997; Semchuk et al., 1992) (Gorell et al., 1998) and increased mortality from PD (Ritz and Yu, 2000). The use of *C. elegans* to study the etiology of PD will be discussed in the later section. This is due to the specificity with which these pesticides target the nigrostriatal DAergic system via an elevation of dopamine and amine turnover (Thiruchelvam et al., 2000a, 2000b). All forms of paraquat are easily reduced to a radical ion, which generates superoxide radical that reacts with unsaturated membrane lipids (Uversky, 2004), a likely mechanism of", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 891, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "a5df1f1c-093d-44d9-a719-bbc0a0160abb": {"__data__": {"id_": "a5df1f1c-093d-44d9-a719-bbc0a0160abb", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.6, para 0](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d8ffec86-43ca-48fb-a46a-7f672c5979fd", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.6, para 0](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "b538b2811390da2ecddc0228cbb93af703196564f09dbeef75bd2baeb0b28856", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "10                                                                                                                        LEUNG ET AL.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 134, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "24970526-31af-4191-b714-e2f9fdf1ea9e": {"__data__": {"id_": "24970526-31af-4191-b714-e2f9fdf1ea9e", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.6, para 1](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a64618ea-8afa-400c-bf27-6b5db555abe2", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.6, para 1](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "6037c00f86247663a2fb5fdb4f906a09faee7115b7afbc41cbf4787371636fd6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "```\n                                                                                                                        TABLE 4\n                                                                                   Pesticides that Have Been Tested Using *Caenorhabditis elegans* as a Model Organism\n```", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 302, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "74a93589-b202-403f-88fe-a8179dae1091": {"__data__": {"id_": "74a93589-b202-403f-88fe-a8179dae1091", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.6, para 2](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2385c250-fd19-4e0d-b116-fd6df24fb6ce", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.6, para 2](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "c035415624e7bdaac9a1de7a4a98f0b50a711d0e0b06e691b352de6f9fb2e57d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Compound|Strains investigated|Observations|References|\n|-|-|-|-|\n|Paraquat|\\`mev-1(kn1)^a\\`, \\`mev-2(kn2)^a\\`\\\\`rad-8(mn162)\\`|Hypersensitive to oxygen and paraquat, decreased SOD activity\\^b\\\\Hypersensitive to oxygen and paraquat, reduced fecundity,\\decreased life span|Ishii \\*et al.\\* (1990)\\Ishii \\*et al.\\* (1993)|\n||\\`age-1(hx542)\\`, \\`age-1(hx546)\\`|Increased catalase and Cu/Zn SOD activity, increased life span\\Vitamin E (antioxidant) inhibits oxidative damage from paraquat\\^b\\|Vanfleteren (1993)\\Goldstein and Modric (1994)|\n||\\`mev-1(kn1)\\`, \\`rad-8(mn162)\\`|Paraquat and high oxygen content inhibit development,\\inversely proportional to life span|Hartman \\*et al.\\* (1995)|\n||\\`age-1(hx546)\\`, \\`daf-16(m26)\\`,\\\\`mev-1(kn1)^a\\`|Increased resistance to paraquat and heat, extended life span,\\increased SOD, and catalase mRNA level only in \\`age-1\\`\\mutant, but not \\`daf-16\\` or \\`mev-1\\`|Yanase \\*et al.\\* (2002)|\n||\\`mev-5(qa5005)^a\\`, \\`mev-6\\`\\\\`(qa5006)^a\\`, \\`mev-7(qa5007)^a\\`|Longevity and sensitivity to paraquat, UV or heat do\\not correlate|Fujii \\*et al.\\* (2005)|\n||\\`mev-1(kn1)\\`, \\`gas-1(fc21)\\`|Overproduction of superoxide anion in submitochondrial\\particles upon paraquat exposure|Kondo \\*et al.\\* (2005)|\n||\\`skn-1(zu67)\\`|Activation of SKN-1 transcription factor, localizes to the\\nucleus following paraquat exposure|Kell \\*et al.\\* (2007)|\n||\\`daf-2(e1370)\\`|Extended animal life span and increased resistance to ROS\\produced by paraquat|Kim and Sun (2007);\\Yang \\*et al.\\* (2007)|\n||Overexpression of GSTO,\\\\`gsto-1\\` RNAi|Increased resistance to paraquat-induced oxidative stress|Burmeister \\*et al.\\* (2008)|\n|Rotenone|\\`gas-1(fc21)\\`|Increased sensitivity to rotenone under hyperoxia|Ishiguro \\*et al.\\* (2001)|\n||\\`pdr-1\\`, \\`djr-1.1\\` RNAi|Increased vulnerability to rotenone|Ved \\*et al.\\* (2005)|\n||Overexpression of LRRK2,\\\\`lrk-1\\` RNAi|Overexpression of wild-type LRRK2 strongly protects\\against rotenone toxicity|Wolozin \\*et al.\\* (2008)|\n|Ops|N2|Computer tracking system is a promising tool for assessing\\neurobehavioral changes associated with OP toxicity\\Cholinesterase inhibition associated with high behavioral toxicity\\Absorption effects are more prominent than biodegradation\\in soil toxicity tests|Williams and\\Dusenbery 1990\\Cole \\*et al.\\* (2004)\\Saffih-Hdadi \\*et al.\\* (2005)|\n|Carbamates|N2|Rank order of toxicity of carbamate pesticides in \\*C. elegans\\*\\correlates well with values for rats and mice, and degree\\of behavioral alteration correlates with AChE inhibition|Melstrom and\\Williams (2007)|\n|\\*Bt\\* toxin|\\`bre-1(ye4)\\`, \\`bre-2(ye31)\\`, \\`bre-3\\`\\\\`(ye28)\\`, \\`bre-4(ye13)\\`, \\`bre-5(ye17)\\`|Extensive damage to gut, decreased fertility, and death|Marroquin \\*et al.\\* (2000)|\n||\\`bre-5(ye17)\\`|Increased resistance to \\*Bt\\* toxin|Griffiths \\*et al.\\* (2001)|\n||\\`bre-2(ye31)\\`, \\`bre-2(ye71)\\`,\\\\`bre-3(ye28)\\`, \\`bre-4(ye13)\\`|\\*Bt\\* toxin resistance involves the loss of glycosyltransferase\\in the intestine|Griffiths \\*et al.\\* (2003)|\n||\\`glp-4(bn2)\\`, \\`kgb-1(um3)\\`,\\\\`jnk-1(gk7)\\`, \\`sek-1(km4)\\`|\\*Bt\\* toxin reduces brood size and causes damage to the intestine\\A p38 MAPK and a c-Jun N-terminal-like MAPK are both\\transcriptionally upregulated by \\*Bt\\* toxin|Wei \\*et al.\\* (2003)\\Huffman \\*et al.\\*\\(2004a, 2004b)|\n|||Survival rate, infection level, and behavior differed in\\\\*C. elegans\\* isolated from geographically distinct strains|Schulenburg and\\Muller (2004)|\n||\\`bre-2(ye31)\\`, \\`bre-3(ye28)\\`,\\\\`bre-4(ye13)\\`, \\`bre-5(ye17)\\`|\\*Bt\\* toxin resistance entails loss of glycolipid carbohydrates and\\the toxin directly and specifically binds to Glycolipids|Griffiths \\*et al.\\* (2005)|\n||\\`bre-3(ye28)\\`|Resistance to \\*Bt\\* toxin develops as a result of loss of glycolipid\\receptors for the toxin|Barrows \\*et al.\\* (2006)|\n||\\`bre-1(ye4)\\`, \\`bre-2(ye31)\\`|Resistance to toxin is achieved by mutations in\\glycosyltransferase genes that glycosylate glycolipid or with\\a loss of the monosaccharide biosynthetic pathway|Barrows \\*et al.\\*\\(2007a, 2007b)|\n||\\`daf-2(e1370)\\`, \\`daf-2(e1368)\\`, \\`age-1\\`\\\\`(hx546)\\`, \\`daf-16(mgDf50)\\`, \\`daf-2(0(m26)\\`|Mutations in the insulin-like receptor pathway lead to\\distinct behavioral responses, including the evasion\\of pathogens and reduced ingestion|Hasshoff \\*et al.\\* (2007)|\n|Captan|\\`hsp-16.48;hsp-16.1::lacZ\\`|Reproduction and growth significantly reduced by \\*Bt\\* toxin\\Stress induction localized to muscle cells of the pharynx\\Inhibits feeding, cessation of muscular contraction|Hoss \\*et al.\\* (2008)\\Jones \\*et al.\\* (1996)|\n|Dithiocarbamate fungicides|\\`hsp-16.48;hsp-16.1::lacZ\\`|Induction of stress response|Guven \\*et al.\\* (1999)|\n|Organochlorinated pesticides|N2|Decreased sensitivity to organochlorinated pesticide in \\*C. elegans\\*\\than other soil invertebrates. Compared to other organic\\pollutants tested, organochlorinated pesticides are the most\\toxic substances in soil or aquatic medium|Bezchlebova \\*et al.\\* (2007);\\Sochova \\*et al.\\* (2007)|\nNote. MAPK, mitogen-activated protein kinase; ROS, reactive oxygen species.\n^aThese mutants showed defective dye filling, indicative of chemosensory neuron damage.\n^bSOD, superoxide dismutase.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 5196, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "40298709-d957-487a-8d00-13995c0e7403": {"__data__": {"id_": "40298709-d957-487a-8d00-13995c0e7403", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.7, para 0](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "979ec489-774d-40b0-a6f3-6848a4290a1d", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.7, para 0](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "575bff1e1228678e12a01d2b448c091381a504d8c584112a3aab1728da66fff0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "CAENORHABDITIS ELEGANS IN TOXICOLOGY RESEARCH                                                                 11", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 112, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b11c16e3-5c6c-48c6-b574-356d3c05e453": {"__data__": {"id_": "b11c16e3-5c6c-48c6-b574-356d3c05e453", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.7, para 1](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f412a94a-c9e1-49f8-9b12-b79893a8d4ff", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.7, para 1](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "22aa7b1cec64a31c3bf68e453a58b2d1b969e8e6656dc1ea655568abd6559556", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "neurotoxicity. *Caenorhabditis elegans*, has a well-defined, yet simple DAergic network, consisting of eight neurons in the hermaphrodite and an additional six neurons located in the tail of the male (Chase and Koelle, 2007) and four DA receptors. Dopamine is known to be required in the modulation of locomotion and in learning in *C. elegans* (Hills et al., 2004; Sanyal et al., 2004; Sawin et al., 2000). To date, several paraquat/mev\u2013altered strains have been generated to study potential pathways in which paraquat exerts its toxic effects. *mev-1* (mutated for the succinate dehydrogenase) (Hartman et al., 1995; Ishii et al., 1990; Kondo et al., 2005) and *mev-3* (Yamamoto et al., 1996) were generated first, and both strains displayed increased sensitivity to paraquat- and oxygen-mediated injury as a result of increased production of superoxide radicals (Guo and Lemire, 2003; Ishii et al., 1990) and hypersensitivity to oxidative stress. *mev-4* (Fujii et al., 2004), *mev-5*, *mev-6*, and *mev-7* (Fujii et al., 2005) displayed resistance to paraquat. However, since the proteins that are encoded by these genes are currently unknown, future mapping of these genes will likely reveal pathways involved in paraquat toxicity.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1236, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b1b5b896-d1fc-4a42-8957-353555c859f2": {"__data__": {"id_": "b1b5b896-d1fc-4a42-8957-353555c859f2", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.7, para 2](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8c8d4b83-6154-4104-a250-0febc679edff", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.7, para 2](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "33c599adad94c3882911ebaafb4cf728510afb2fd4a4f42182bf7b46868ec339", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Paraquat exerts oxidative damage in vertebrates, which has also been corroborated in *C. elegans*. Mutants that lack antioxidant enzymes such as cytosolic or mitochondrial superoxide dismutases (*sod-1* and *sod-2*) show increased sensitivity to paraquat (Yang et al., 2007), whereas mutants with increased superoxide dismutase levels, such as *age-1* (encoding the catalytic subunit of phosphoinositide 3-kinase) (Vanfleteren, 1993; Yanase et al., 2002) and worms overexpressing the omega-class glutathione transferase *gsto-1* (Burmeister et al., 2008) display increased resistance to paraquat toxicity. Moreover, *C. elegans* mutants hypersensitive to oxygen toxicity, such as *rad-8* (Honda et al., 1993; Ishii et al., 1990) or those with a prolonged life span, such as *daf-2* (encoding insulin/insulin growth factor receptor) (Bardin et al., 1994; Kim and Sun, 2007) show increased tolerance to paraquat. Taken together, these results provide novel information on mechanisms by which paraquat mediates its toxicity (by enhancing sensitivity to oxygen toxicity with an elevation in production of reactive oxygen species and shortening life span) and provide directions for future investigations on mechanisms that lead to DAergic neurodegeneration.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1253, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0dfc1340-658e-40fd-86e1-4c13a41fab9e": {"__data__": {"id_": "0dfc1340-658e-40fd-86e1-4c13a41fab9e", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.7, para 3](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b4ba1250-e1d9-4c2f-aa22-90c28850beab", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.7, para 3](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "5e8a9f3bac1ec352932c31b5dc0eae34edbd440525855b1243f8369e5c554a76", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "A second ubiquitous pesticide is rotenone; it is a naturally occurring and biodegradable pesticide effective in killing pests and fish (Uversky, 2004). Researchers first reported in 2000 that Iv exposure to rotenone may lead in humans to the development of PD-like symptoms accompanied by the selective destruction of nigral DAergic neurons (Betarbet et al., 2000). Since rotenone acts by inhibiting mitochondrial NADH dehydrogenase within complex I (Gao et al., 2003), the development of a mutant *C. elegans* strain that exhibits mitochondrial inhibition provided an experimental platform where the role of this enzyme could be directly evaluated. A mutation in a 49-kDa subunit of mitochondrial complex I in", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 710, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3d901c67-1420-4771-ae8f-9290e7a70deb": {"__data__": {"id_": "3d901c67-1420-4771-ae8f-9290e7a70deb", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.7, para 4](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5b90ead1-decb-450d-9b96-35ea00c8305b", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.7, para 4](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "a30ec4aee78155041dc23c10381421bcf895091f8b8d761a9b6c64fdf982e43f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "*C. elegans* mutant *gas-1* displays hypersensitivity to rotenone and oxygen (Ishiguro et al., 2001), highlighting the importance of a functional complex I in rotenone resistance. Moreover, *C. elegans* with alterations in PD causative genes are highly sensitive to rotenone toxicity, suggesting the ability of these proteins to protect against rotenone-induced oxidative damage in DAergic neurons (Ved et al., 2005; Wolozin et al., 2008) (see neurodegenerative disease section below).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 485, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1b37f9a6-98f6-4ddf-a668-8caabe4b07da": {"__data__": {"id_": "1b37f9a6-98f6-4ddf-a668-8caabe4b07da", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.7, para 5](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6692e3cf-e306-44ee-bad7-2cf099d9ca67", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.7, para 5](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "6f0df003bd06e51fca92444f71fd1a01221eef288cfc0ac1cbad704544693590", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The organophosphates (OPs) are a group of insecticides that target the cholinergic system. ACh is the primary neurotransmitter involved in motor function in most organisms, including the nematode (Rand and Nonet, 1997). Due to the involvement of the neuromuscular system, a computer tracking system was used to study the neurobehavioral changes in *C. elegans* associated with two OP pesticides (malathion and vapona). *Caenorhabditis elegans* showed a remarkable decline in locomotion at a concentration below survival reduction (Williams and Dusenbery, 1990b). Comparison studies using similar behavioral analyses were later developed to assess movement alteration as an indicator of the neurotoxicity of 15 OP pesticides (Cole et al., 2004) and carbamate pesticides, which unlike OP pesticides are reversible AChE inhibitors (Melstrom and Williams, 2007). The LD50 values in *C. elegans* closely correlated with LD50 in both rats and mice. Pesticides (vapon, parathion, methyl parathion, methidathion, and funsulfothion) that showed cholinesterase inhibition were associated with pronounced behavioral toxicity (i.e., decrease in movement). A recent study has compared end points using OPs and found AChE inhibition to be the most sensitive indicator of toxicity but also the most difficult to measure (Rajini et al., in press). Reduction in movement for 10 OPs was found to correlate to rat and mouse acute lethality data. Finally, simulation studies examining the rate of absorption and biodegradation of OP (parathion) also (Saffih-Hdadi et al., 2005) establish the relevance and reliability of *C. elegans* as an experimental model and predictor for soil toxicity.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1671, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5c6657d3-7491-4914-8a33-a0aa89742aee": {"__data__": {"id_": "5c6657d3-7491-4914-8a33-a0aa89742aee", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.7, para 6](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f7c54a09-8aa3-4849-8a5e-b1ec7cf611de", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.7, para 6](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "3ddf50b9b61bf2d87178b6e51c11abafeb42f64a0a29abe421aed4fd96cf1091", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Caenorhabditis elegans in the Study of Neurodegeneration", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 59, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "589fe71e-6bab-4aa4-9e65-94671613a881": {"__data__": {"id_": "589fe71e-6bab-4aa4-9e65-94671613a881", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.7, para 7](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b918a0fd-0795-4d86-a9ee-241997330a83", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.7, para 7](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "c33e8830daca908835a06f3240ca666a4bbb5736000213f0131e4e6077dea28b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "As previously stated, the *C. elegans* nervous system functionally recapitulates many of the characteristics of the vertebrate brain. In particular, it can undergo degeneration through conserved mechanisms and is thus a powerful model for uncovering the genetic basis of neurodegenerative disorders. In this section, we will focus on PD, Alzheimer disease (AD), Huntington disease (HD), and Duchenne muscular dystrophy (DMD).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 425, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "80566165-7a9a-49df-a58b-e4a597f6c03d": {"__data__": {"id_": "80566165-7a9a-49df-a58b-e4a597f6c03d", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.7, para 8](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "546057cb-3e04-43e1-b600-ec4bfe5488bc", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.7, para 8](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "17bdc4d21d1290090cd212df77a46e742e959d6987a66ba67de328a49e11db84", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "PD is a progressive, neurodegenerative disorder afflicting \\~2% of the U.S. population (Bushnell and Martin, 1999). Characteristic features include a gradual loss of motor function due to the degeneration of DAergic neurons within the substantia nigra pars compacta and loss of DAergic terminals in the striatum (Wilson et al., 1996). At the cellular level,", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 357, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cbea9a62-ef1d-4a85-9945-be5725b44c45": {"__data__": {"id_": "cbea9a62-ef1d-4a85-9945-be5725b44c45", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.8, para 0](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bf05494c-6473-4155-8fd5-32993899b705", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.8, para 0](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "ee7f1427771540787f17caba90b433b78501f7c31800b6de3fe370ad4db2e74f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "deposition of cytoplasmic Lewy bodies composed of aggregated protein, such as \u03b1-synuclein, is observed. PD cases are referred as familial (FPD) or idiopathic (IPD) depending on whether the disease is hereditary (FPD) or from unknown origin, possibly due to environmental exposure to neurotoxicants (IPD) (Dauer and Przedborski, 2003; Samii et al., 2004). Among 11 genomic regions (PARK1 to 11) associated with FPD, 7 were narrowed down to single genes: PARK1 (\u03b1-SYNUCLEIN), PARK2 (PARKIN), PARK4 (\u03b1-SYNUCLEIN), PARK5 (UCHL1), PARK6 (PINK1), PARK7 (DJ1), PARK8 (DARDARIN/LRRK2), and PARK9 (ATP13A2) (Wood-Kaczmar et al., 2006). All but \u03b1-SYNUCLEIN are strictly conserved in the nematode with most residue positions mutated in PD patients encoding identical amino acids in C. elegans orthologues (Benedetto et al., 2008). Worms overexpressing wild type, mutant A30P, or A53T human \u03b1-SYNUCLEIN in DAergic neurons show differential levels of injury, including reduced DA content, DAergic neuron degeneration, motor deficits reversible by DA administration, intracellular \u03b1-SYNUCLEIN aggregates similar to Lewy bodies, and increased vulnerability to mitochondrial complex-I inhibitors, which is reversed by treatment with antioxidants (Kuwahara et al., 2006; Lakso et al., 2003; Ved et al., 2005). Furthermore, deletion (Springer et al., 2005) and knockdown of the C. elegans PARKIN and DJ1 genes produce similar patterns of pharmacological vulnerability as those described above for \u03b1-SYNUCLEIN overexpression (Ved et al., 2005). Other PD genes in C. elegans have been investigated. For example, ubh-1 and ubh-3 (Chiaki Fujitake et al., 2004) share similar functions with the human PARK5/UCHL1 orthologue. Studies on other genes have been instrumental in unraveling previously unknown functions. For example, examination of the PARK8/DARDARIN orthologue lrk-1 showed that the protein allows the proper targeting of synaptic vesicle proteins to the axon (Sakaguchi-Nakashima et al., 2007) and protects against rotenone-induced mitochondrial injury (Wolozin et al., 2008). Recently, RNAi, genomic, and proteomic approaches using human \u03b1-SYNUCLEIN transgenic worms identified genetic networks linking PD to G-protein signaling, endomembrane trafficking, actin cytoskeleton, and oxidative stress (Cooper et al., 2006; Gitler et al., 2008; Hamamichi et al., 2008; Ichibangase et al., 2008; van Ham et al., 2008; Vartiainen et al., 2006), illustrating the power of this transgenic model for PD study.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2490, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "08bb972c-2e73-4b67-a699-f1e45299ec60": {"__data__": {"id_": "08bb972c-2e73-4b67-a699-f1e45299ec60", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.8, para 1](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "79e150f8-2d7e-46e2-899d-5df714a5024a", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.8, para 1](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "cd59efd6a3f63ebfb86540ec0ae588e754a44846797d3519a0f041ee6863adc9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Nonhereditary PD cases have also been associated with exposure to 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine, a designer drug that is converted intracerebrally (by astrocytes) to 1-methyl-4-phenylpyridinium (MPP+) by the monoamine oxygenase B. MPP+ damages the DAergic nervous system, leading to a typical Parkinsonian syndrome (Kopin and Markey, 1988; Langston et al., 1984). Similarly, MPP+-exposed C. elegans show specific degeneration of DAergic neurons and associated behavioral defects (Braungart et al., 2004), which is due to ATP depletion (Wang et al., 2007b). Exposures to rotenone (see above) or 6-hydroxydopamine also lead to PD syndromes that share similar features both in humans and worms (Cao et al., 2005; Ishiguro et al., 2001; Marvanova and Nichols, 2007; Nass et al., 2002, 2005; Ved et al., 2005). Though the nematode does not truly exhibit PD-like symptoms, results with transgenic and drug-exposed worms emphasize the relevance of C. elegans as a model organism that (1) permits rapid insights in the genetic pathways involved in PD and (2) enables high-throughput screening methods for the development of new anti-PD drugs (Schmidt et al., 2007).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1172, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2d7ce1ce-5d70-4d77-a792-83c9f67abecd": {"__data__": {"id_": "2d7ce1ce-5d70-4d77-a792-83c9f67abecd", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.8, para 2](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "35329890-b735-4191-9b91-84c405541ae7", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.8, para 2](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "9f554fbde11391c7ac2c80286d45eaeca406bc7ba2c5de3640b4b6112ba80677", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Tauopathies and polyglutamine extension disorders have also been investigated in the worm using mutants and transgenic strains (Brandt et al., 2007; Dickey et al., 2006, Link, 2001; Kraemer et al., 2003, 2006, and Kraemer and Schellenberg, 2007). The first AD-associated proteins identified were the beta-amyloid peptide precursor (betaAPP) and the presenilins PS1 and PS2. Study of the C. elegans presenilin orthologues sel-12 (Baumeister et al., 1997; Levitan and Greenwald, 1995) and hop-1 (Li and Greenwald, 1997; Smialowska and Baumeister, 2006) linked AD to the apoptotic pathway (Kitagawa et al., 2003) and Notch signaling, which was later confirmed in vertebrates (Berezovska et al., 1998, 1999; Ray et al., 1999). Characterization of the C. elegans betaAPP orthologue revealed a key role for microRNA in AD gene regulation (Niwa et al., 2008). However, most of the knowledge about AD acquired in C. elegans came from two transgenic models: worms expressing the human betaAPP (Boyd-Kimball et al., 2006; Drake et al., 2003; Gutierrez-Zepeda and Luo, 2004; Wu and Luo, 2005; Wu et al., 2006) or TAU (Brandt et al., in press; Kraemer et al., 2003). Studies on betaAPP transgenic worms revealed toxicity mechanisms of AD by identifying two new genes, aph-1 and pen-2, likely involved in the progression of the disease (Boyd-Kimball et al., 2006; Francis et al., 2002). They also allowed the characterization of oxidation processes preceding fibrillar deposition (Drake et al., 2003) and the identification of genes activated upon induction of betaAPP expression (Link et al., 2003). Furthermore, protective mechanisms were identified (Florez-McClure et al., 2007; Fonte et al., 2008) and potential therapeutic drugs for AD (ginkgolides, Ginkgo biloba extract EGb 761, soy isoflavone glycitein) were originally and successfully assayed in worms (Gutierrez-Zepeda et al., 2005; Luo, 2006; Wu et al., 2006). Caenorhabditis elegans overexpressing the human TAU or a pseudohyperphosphorylated mutant TAU were found to exhibit age-dependent motor neuron dysfunctions, neurodegeneration, and locomotor defects due to impaired neurotransmission (Brandt et al., 2007; Kraemer et al., 2003).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2186, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "7a5f6f0f-3fd4-4c2e-8c4a-37206a614d13": {"__data__": {"id_": "7a5f6f0f-3fd4-4c2e-8c4a-37206a614d13", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.8, para 3](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7a379a4b-145d-4ffc-983a-1b2491790843", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.8, para 3](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "7520f1813f980a47b242c167a7797bb0b1cba09bdf202405622261dee0ce7216", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Likewise, while a few Huntingtin (Htt)-interacting genes were identified in C. elegans (Chopra et al., 2000; Holbert et al., 2003), most data came from transgenic worms expressing polyQ variants of Htt. Several groups targeted different neuronal subsets to study polyQHtt neurotoxicity in the worm. They described behavioral defects prior to neurodegeneration and protein aggregation and axonal defects and uncovered a role for apoptosis in HD neurodegeneration (Bates et al., 2006; Faber", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 488, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "34749386-6e76-4e55-b5ce-f0a45bc37118": {"__data__": {"id_": "34749386-6e76-4e55-b5ce-f0a45bc37118", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.9, para 1](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f66f1876-9162-4df3-8284-da5a2a0f4c52", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.9, para 1](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "97b259d295053ee11da46600e958a3468cb23d49807cbde2d28df90bd6cf6835", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "et al., 1999; Holbert et al., 2003; Parker et al., 2001). Protective mechanisms of the polyQ enhancer-1 and ubiquilin were demonstrated (Faber et al. 2002; Wang et al., 2006), and pharmacological screening using polyQHtt transgenic C. elegans is ongoing (Faber et al. 2002; Wang et al., 2006).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 293, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "df3bd953-fc4d-4eb9-8120-8da4a990b490": {"__data__": {"id_": "df3bd953-fc4d-4eb9-8120-8da4a990b490", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.9, para 2](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2ced2e80-8522-4c7b-995c-f4be6911b339", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.9, para 2](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "1a3f907ea7920a49c06516031904c4e60a206fd0cbfb24d49376237888d61062", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "A final illustration of the successful use of C. elegans in elucidating the genetic basis of neurodegenerative disorder is exemplified by the characterization of the genetic network implicated in DMD. DMD is mainly characterized by a progressive loss of muscular mass and function occurring in males due to mutations in the DYSTROPHIN gene located on the X chromosome, which commonly leads to paralysis and death by the age of 30. DYSTROPHIN is both muscular and neuronal, being required for brain architecture and neurotransmission, such that DMD patients exhibit neurodegeneration associated with motor deficits and reduced cognitive performances (average IQ is 85 in DMD boys) (Anderson et al., 2002; Blake and Kroger, 2000; Poysky, 2007). DYSTROPHIN is conserved in C. elegans, but its loss-of-function in the worm results in hypercontractility due to impaired cholinergic activity and does not affect muscle cells (Bessou et al., 1998; Gieseler et al., 1999b). Nevertheless, the observation that double mutants for Dystrophin/dys-1 and MyoD/hlh-1 display severe and progressive muscle degeneration in the worm (as observed in mice), set up the basis for a C. elegans model to study dystrophin-dependent myopathies (Gieseler et al., 2000). Using this model, several partners of DYSTROPHIN were characterized, establishing their role in cholinergic neurotransmission and muscle degeneration (Gieseler et al., 1999a, 1999b, 2001; Grisoni et al., 2002a, 2002b, 2003). Additionally, it was shown that the overexpression of DYSTROBREVIN/dyb-1 delays neurological and muscular defects (Gieseler et al., 2002), and mutations in CHIP/chn-1, chemical inhibition of the proteasome, and prednisone or serotonin treatments suppress muscle degeneration in C. elegans (Carre-Pierrat et al., 2006; Gaud et al., 2004; Nyamsuren et al., 2007).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1830, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "481484d0-7e72-4025-9e05-95dc7bbc41b6": {"__data__": {"id_": "481484d0-7e72-4025-9e05-95dc7bbc41b6", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.9, para 3](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f638b2a9-e1aa-4919-81ee-b3ccca068b0c", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.9, para 3](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "a9ab199642580f76a20681b10467fea0f59ec4cb13893b1edc7ee17c109112d6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Thus, though at first glance C. elegans appears quite different from vertebrates, its nervous circuitry and the cellular processes guiding neuronal development, neuronal death or survival, neurotransmission, and signal integration rely on the same neuronal and molecular networks as vertebrates. Combined with the advantages of a small and fast-growing organism, these properties make C. elegans a perfect system for rapid genetic analysis of neurotoxicity mechanisms.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 468, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8670bbb7-d902-4460-b261-af66b0e35fab": {"__data__": {"id_": "8670bbb7-d902-4460-b261-af66b0e35fab", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.9, para 4](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "447d5eda-77ca-4389-83b4-235d59f99be6", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.9, para 4](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "9e4fdbd5ac7ca22309a5a91b4922457aa7f0e66afefa9960981705f29f8e884a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "cesses related to DNA damage have been extensively studied in C. elegans, providing an important biological context and clear relevance to mechanistic studies. Finally, powerful tools for the study of DNA damage, DNA repair, and mutations have been developed in this organism.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 276, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "977da58f-524f-47ac-b6ce-1fc585a872d3": {"__data__": {"id_": "977da58f-524f-47ac-b6ce-1fc585a872d3", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.9, para 5](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a2426973-6163-4425-a5b6-a7a6afee0c07", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.9, para 5](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "ffdec0fb8cfc11c00d76a212997075be5ce4a3485bb1968ccc05af6e4d48e41a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## DNA Damage Response Proteins Are Conserved between C. elegans and Higher Eukaryotes", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 86, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c6eda8e5-d422-486c-a640-7481e47ee3ab": {"__data__": {"id_": "c6eda8e5-d422-486c-a640-7481e47ee3ab", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.9, para 6](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "95c3bcd5-d548-4080-b8a1-f47c922892eb", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.9, para 6](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "7214d19aaa0c10cc42bc96b3eaae7163bfbbc6589baaa9da5fc2dce7bfa2598e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Genes and pathways involved in DNA repair in mammals are generally well conserved in C. elegans (Boulton et al., 2002; Hartman and Nelson, 1998; O\u2019Neil and Rose, 2005). Proteins involved in nucleotide excision repair, mismatch repair, homologous recombination, and nonhomologous end joining, for instance, are almost entirely conserved between C. elegans, mouse, and human based on nucleotide sequence homology (", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 412, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f5728ed7-2933-46b3-bef9-bf6b0876d41a": {"__data__": {"id_": "f5728ed7-2933-46b3-bef9-bf6b0876d41a", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.9, para 7](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "66353796-f38e-409b-aa8e-c6c52dc9b49d", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.9, para 7](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "b536937e3e45b091c5751f0851eb47aba38f34284539d01858c727f6b7ed4e21", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "). This is also true for proteins involved in many DNA repair\u2013related processes, such as translesion DNA polymerases, helicases, and nucleases. Base excision repair proteins, interestingly, show somewhat less conservation. While this conservation is based in some cases only on sequence homology, many of these proteins have now been biochemically or genetically characterized. Critically, proteins involved in other DNA damage responses including apoptosis and cell cycle arrest are also conserved in C. elegans and mammals (Stergiou and Hengartner, 2004).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 557, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6b03a1bc-20e0-4d92-9578-ec695fec479c": {"__data__": {"id_": "6b03a1bc-20e0-4d92-9578-ec695fec479c", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.9, para 8](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "624df299-a68c-4b21-a224-55dd3f0164b5", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.9, para 8](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "3d7d3bf1eb620b7f55800c0e1e35e92bde4ad8a1f3958d52971dd01cb471c139", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## DNA Repair in C. elegans", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 27, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e0696684-3bc2-4f7c-bf12-566332ecd8fb": {"__data__": {"id_": "e0696684-3bc2-4f7c-bf12-566332ecd8fb", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.9, para 9](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ee0923f2-6183-43fd-b527-60372eb20aab", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.9, para 9](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "e6e743b22595f66bd6d046cad979dbde971e7289a947ffb23f370e74b8d3479b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Early studies on DNA repair in C. elegans were carried out by Hartman and colleagues, who identified a series of radiation-sensitive mutants (Hartman, 1985; Hartman and Herman, 1982) and used an antibody-based assay to measure induction and repair of ultraviolet (UV) radiation-induced damage (Hartman et al., 1989). These and more recent studies (Hyun et al., 2008; Meyer et al., 2007) have shown that nucleotide excision repair is similar in C. elegans and humans both in terms of conservation of genes and kinetics of repair. Nucleotide excision repair is a critical pathway in the context of exposure to environmental toxins since it recognizes and repairs a wide variety of bulky, helix-distorting DNA lesions, including polycyclic aromatic hydrocarbon metabolites, mycotoxins such as aflatoxin B1, UV photoproducts, cisplatin adducts, and others (Friedberg et al., 2006; Truglio et al., 2006).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 899, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "428aaf35-1be6-4bfd-8528-adff5e3fb3a8": {"__data__": {"id_": "428aaf35-1be6-4bfd-8528-adff5e3fb3a8", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.9, para 10](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "55e8642d-b15f-4022-9715-5c4f6b51705c", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.9, para 10](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "eb28bbd4f9b000a4e10604396ac5adbd68443701ece69ecc0d247ce2ba846f9a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "While nucleotide excision repair has been the best-studied DNA repair pathway in C. elegans, significant progress has been made in the study of genes involved in other DNA repair pathways as well. The role of specific C. elegans gene products in DNA repair has been studied both via high-throughput and low-throughput methods. High-throughput methods including", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 360, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fde03830-4741-439d-b021-fbf06f6a92a3": {"__data__": {"id_": "fde03830-4741-439d-b021-fbf06f6a92a3", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.9, para 11](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5e54fa2a-a48a-44fb-9ecf-0753676b061c", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.9, para 11](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "0ad7a5a23600148477e0947e132d34477deaa80f9176d9824aae4fafd37077ec", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "### Caenorhabditis elegans AND GENOTOXICITY", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 43, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b12199ae-d73f-46a9-82c8-b09c812a6654": {"__data__": {"id_": "b12199ae-d73f-46a9-82c8-b09c812a6654", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.9, para 12](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5b110e2c-cad2-45fd-a03c-a18d96411c7a", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.9, para 12](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "d4af2a3e0546df1cf0b0bbe604e74f418bfd539cbba655083ed2f9a538d9b270", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "As is the case for neurotoxicity, C. elegans provides a cost-effective, in vivo, genetically manipulable and physiological model for the study of the toxicological consequences of DNA damage. As described below, the machinery that responds to DNA damage in C. elegans is very similar genetically to the corresponding machinery in higher eukaryotes. Many pro-", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 358, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c2aa6fa5-11fe-467b-b6b8-1e693f02805d": {"__data__": {"id_": "c2aa6fa5-11fe-467b-b6b8-1e693f02805d", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.10, para 0](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c978bc44-c81b-4e4b-9ca3-63dc2feeb531", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.10, para 0](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "96e708c41749817341b1162e366c7d9aa8ef10e4fec3aec672b88bd20432e14f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "14                                                      LEUNG ET AL.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 68, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0baf623d-ca51-4fdf-ae29-1edcf1794337": {"__data__": {"id_": "0baf623d-ca51-4fdf-ae29-1edcf1794337", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.10, para 1](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bf306eb3-1cca-4f6b-ace6-2d9172e55912", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.10, para 1](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "f55d60d2788519f15f020e557d21b4e0feb8acdde477e6d0488be49a24b58bd6", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "RNAi knockdown and yeast two-hybrid analysis of protein-protein interaction have been used to identify a large number of genes coding for proteins involved in responding to DNA damage (Boulton et al., 2002; van Haaften et al., 2004a, 2004b). Lower throughput studies involving biochemical analyses of DNA repair activities (Dequen et al., 2005a; Gagnon et al., 2002; Hevelone and Hartman, 1988; Kanugula and Pegg, 2001; Munakata and Morohoshi, 1986; Shatilla et al., 2005a, 2005b; Shatilla and Ramotar, 2002) as well in vivo sensitivity to DNA damaging agents (Astin et al., 2008; Boulton et al., 2004; Dequen et al., 2005b; Lee et al., 2002, 2004; Park et al. 2002, 2004; St-Laurent et al., 2007) or other DNA damage\u2013related phenotypes (Aoki et al., 2000; Kelly et al., 2000; Sadaie and Sadaie, 1989; Takanami et al., 1998) have supported the sequence similarity\u2013based identification of *C. elegans* homologues of DNA repair genes in higher vertebrates, as well as in some cases permitting identification of previously unknown genes involved in these pathways.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1061, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8898a961-84f6-4571-bddb-9a10c5170eac": {"__data__": {"id_": "8898a961-84f6-4571-bddb-9a10c5170eac", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.10, para 2](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a8618bea-468f-402e-a085-7a8aa5d644e9", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.10, para 2](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "2228bca3fa4389a6b534356df56b50da727cf650740ec867c926ebf861a95f87", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "and Kenyon, 2007; Poulin et al., 2004; Sherwood et al., 2005; van Haaften et al., 2004a), aging (Antebi, 2007; Brys et al., 2007; Hartman et al., 1988; Johnson, 2003; Kenyon, 2005; Klass, 1977; Klass et al., 1983; Murakami, 2007; Rea et al., 2007; Ventura et al., 2006), and neurodegenerative diseases (described above) are also areas of active research in *C. elegans*. This research has both established the relevance of *C. elegans* as a model for the study of genotoxic agents (due to conservation of the DNA damage response) and enormously increased its utility in such studies by providing a wealth of complementary and contextual biological information related to the pathological responses to DNA damage in this organism.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 729, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8f2606c7-9cd0-4418-8415-c16d7f4353f1": {"__data__": {"id_": "8f2606c7-9cd0-4418-8415-c16d7f4353f1", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.10, para 3](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c8ce5c37-7301-4e32-8c60-ba2ef83cd760", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.10, para 3](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "4e0736fb6821354945c4ff506d2137970fd2e6bbf26e65afbd870c537d4c6734", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Tools for the Study of DNA Damage, Repair, and Mutation in *C. elegans*", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 74, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "bea1cc48-a3e6-48c6-8532-3170de95e64d": {"__data__": {"id_": "bea1cc48-a3e6-48c6-8532-3170de95e64d", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.10, para 4](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "653b04bc-ab4c-47a1-865d-2e0e5dbf0059", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.10, para 4](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "58fe6f95c5f6a262d65baa37f287d3e0054eda00c33d3e82c009ac72531b2f5c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "*Caenorhabditis elegans* is an excellent model for studies of genotoxicity due to the plethora of powerful tools available. Genetic manipulation via RNAi and generation of KOs or other mutants is relatively straightforward. If suitable mutants are not already available, they can be generated by a variety of approaches. These include untargeted and targeted methods, including chemical mutagenesis, transposon insertion, and biolistic transformation (Anderson, 1995; Barrett et al., 2004; Berezikov et al., 2004; Plasterk, 1995; Plasterk and Groenen, 1992; Rushforth et al., 1993).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 582, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e23c77c1-d17e-472c-b93c-7f39c6d211a2": {"__data__": {"id_": "e23c77c1-d17e-472c-b93c-7f39c6d211a2", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.10, para 5](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "e77213b5-8838-4bad-af1c-ef57e18337f3", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.10, para 5](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "14fd65889c19bbd6096a4eccf1d43a544c9f01061bc460ecce9db5d698976136", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Assays for the measurement of mutagenesis, DNA damage and repair, and transcriptional activity have also been developed for genotoxicity assessment in *C. elegans* (Table 5). Some DNA damage and repair assays in *C. elegans* can be carried out with as few as one or a few individual nematodes, permitting studies of interindividual differences and permitting high-throughput screening of DNA- damaging agents or genes involved in DNA repair. It is also possible, using PCR- or Southern blot\u2013based methods, to distinguish damage and repair in different genomic regions and genomes (i.e., mitochondrial vs. nuclear DNA; (Hyun et al., 2008; Meyer et al., 2007)). Mutagenesis has been studied by a variety of methods (Table 5) including phenotype-based genetic mutation reversion screens, an out-of-frame LacZ transgene reporter, and direct sequencing.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 848, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8172855c-66d6-4ce9-8050-c8cc1091948e": {"__data__": {"id_": "8172855c-66d6-4ce9-8050-c8cc1091948e", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.10, para 6](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4cb7edb8-f873-47c1-8127-cbf6d9eb271d", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.10, para 6](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "4d5794a66ab538ac1952cb443f4491530f940193df46eaa8756f1241f4dd73fb", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Apoptosis and Cell Cycle Checkpoints in *C. elegans*", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 55, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8b2028d4-7682-40ce-ab70-cbcc7b633bb2": {"__data__": {"id_": "8b2028d4-7682-40ce-ab70-cbcc7b633bb2", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.10, para 7](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "85ddb58f-a8a9-422e-bb8c-bc7103257a01", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.10, para 7](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "d447ae7a59d6f25e4902a233636835d410dfaed50686e08026f71404310d6421", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "DNA damage that is not repaired can trigger cell cycle arrest and apoptosis, and these pathways are very well studied in *C. elegans*. The great progress made in understanding them mechanistically demonstrates the power of this model organism. As mentioned, the cellular mechanisms regulating apoptosis were discovered in *C. elegans*, and apoptosis and cell cycle responses to DNA damage continue to be heavily studied in *C. elegans* (Ahmed et al., 2001; Ahmed and Hodgkin, 2000; Conradt and Xue, 2005; Gartner et al., 2000; Jagasia et al., 2005; Kinchen and Hengartner, 2005; Lettre and Hengartner, 2006; Olsen et al., 2006; Schumacher et al., 2005; Stergiou et al., 2007). The short life span of *C. elegans* has especially lent itself to groundbreaking studies on the mechanisms of germ line immortality (Ahmed, 2006; Ahmed and Hodgkin, 2000). Another important advantage of *C. elegans* is the ability to easily study in vivo phenomena such as age- or developmental stage\u2013related differences in DNA repair capacity. For example, Clejan et al. (2006) showed that the error-prone DNA repair pathway of nonhomologous end joining has little or no role in the repair of DNA double-strand breaks in germ cells but is functional in somatic cells. Holway et al. (2006) showed that checkpoint silencing in response to DNA damage occurs in developing embryos but not in the germ line. Both these findings are important in our understanding developmental exposure to genotoxins in that they suggest a special protection for germ line cells.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1535, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6d80743d-3973-4ced-9b3e-91805dd26709": {"__data__": {"id_": "6d80743d-3973-4ced-9b3e-91805dd26709", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.10, para 8](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "03c2c614-43f9-4c5c-9044-a91f0984590a", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.10, para 8](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "c4d602b99b77ce8757545c4129b54903b01b84e7c3ea928cc02a8ea99e43892e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Genotoxin Studies in *C. elegans*", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 36, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5330e444-5fd0-4016-bc52-98759049e56b": {"__data__": {"id_": "5330e444-5fd0-4016-bc52-98759049e56b", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.10, para 9](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "97c0a4a8-f889-4412-ae67-e195887d42b7", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.10, para 9](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "8b1a476fa06e3cacdb7037150343b482641d30afab5c11f687a14672cca41572", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Unlike the case of neurotoxicology, there have so far been relatively few studies of genotoxicity per se using *C. elegans*. One exception has been the study of UV radiation, typically as a model genotoxin that introduces bulky DNA lesions (Astin et al., 2008; Coohill et al., 1988; Hartman, 1984; Hartman et al., 1988; Hyun et al., 2008; Jones and Hartman, 1996; Keller et al., 1987; Meyer et al., 2007; Stergiou et al., 2007; Stewart et al., 1991). However, other classes of genotoxins have been studied, including ionizing radiation (Dequen et al.,", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 551, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "975b1336-04ef-4d7d-8976-475d2549c737": {"__data__": {"id_": "975b1336-04ef-4d7d-8976-475d2549c737", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.10, para 10](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a7638aa3-65c0-48d2-93dd-ddd20bb9e3e8", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.10, para 10](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "58eb95b22b21bdc0fa8476d4d74d82e7a87a032bb5f3179459909ad2d544c91c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## DNA Damage\u2013Related Pathological Processes in *C. elegans*", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 60, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6ce0b9d8-cb94-44a8-8805-94c12ad89349": {"__data__": {"id_": "6ce0b9d8-cb94-44a8-8805-94c12ad89349", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.10, para 11](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "884cc4f6-c6df-460c-b50f-a5889eb5e82b", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.10, para 11](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "b63b12ac6c2373386d6d3ed0964d6bd6647eabeca9a4db158d923bb9f6adc7dd", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "DNA damage\u2013related pathological processes including carcinogenesis (He et al., 2007; Kroll, 2007; Pinkston-Gosse", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 112, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0d0e4a6f-d8a8-40df-9c74-5db10fbcf163": {"__data__": {"id_": "0d0e4a6f-d8a8-40df-9c74-5db10fbcf163", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.11, para 1](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a12ba291-138b-42c6-95e5-e91a7e370007", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.11, para 1](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "da517848578c40ec82f174e914f5850a4a570889b92044be8b396c3cbcb6b11d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "TABLE 5\nGenotoxicity Assays Available for the *Caenorhabditis elegans* Model", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 76, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "faeeb4bb-9550-4e8c-8b22-5de08c8fbf8a": {"__data__": {"id_": "faeeb4bb-9550-4e8c-8b22-5de08c8fbf8a", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.11, para 2](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6e11ef9d-6f5b-4e87-b31d-abb15a8abaa5", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.11, para 2](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "cab8baadb7d7527767fb897ae10a7e0e3060ad43c80d0107fa39779aca110c4a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Endpoint|Assay|Principle|References|\n|-|-|-|-|\n|A. Mutagenesis|Direct sequencing|The mutation rate of a given locus is calculated using data from DNA sequencing.|Denver \\*et al.\\* (2000, 2004, 2006)|\n||\u201cBig blue worms\u201d|Transgenic \\*C. elegans\\* carrying an out-of-frame LacZ reporter gene expresses blue pigment upon frameshift or insertion/deletion mutations.|Pothof \\*et al.\\* (2003); Tijsterman \\*et al.\\* (2002)|\n||Reversion assay|Mutants with an easily scored phenotype (e.g., uncoordinated movement) are exposed to a chemical of interest; the restoration of a normal phenotype indicates mutagenesis.|Degtyareva \\*et al.\\* (2002); Greenwald and Horvitz (1980); Hartman \\*et al.\\* (1995)|\n||Lethality assay|The lethality of transgenic, mutation-sensitive \\*C. elegans\\* was measured for mutagen detection|Rosenbluth \\*et al.\\* (1983); Rosenbluth \\*et al.\\* (1985)|\n|B. DNA damage and repair|PCR-based assay|The amount of PCR product is inversely proportional to the amount of DNA damage on a given length of template|Meyer \\*et al.\\* (2007); Neher and Sturzenbaum (2006)|\n||Southern blot|T4 endonuclease\u2013sensitive sites in specific genes (identified by genomic DNA sequence) indicate the presence of UV photodimers|Hyun \\*et al.\\* (2008)|\n||Immunoassay|Antibodies to specific UV photoproducts are identified|Hartman \\*et al.\\* (1989)|\n||Enzymatic activity|A diagnostic enzymatic activity is measured \\*in vitro\\*|Shatilla and Ramotar (2002)|\n||Reproduction/development assay with KO mutants|Specific DNA damage (e.g., DNA adduct) can be tested using simple reproduction/development assays with mutants lacking a specific DNA repair pathway (e.g., nucleotide excision repair)|Park \\*et al.\\* (2002, 2004)|\n|C. Transcriptional activities|RNA: DNA ratio|A decrease in RNA: DNA ratio indicates the inhibition of transcriptional activities|Ibiam and Grant (2005)|\n2005a; Johnson and Hartman, 1988; Stergiou *et al.*, 2007; Weidhaas *et al.*, 2006), heavy metals (Cui *et al.*, 2007b; Neher and Sturzenbaum, 2006; Wang *et al.*, 2008), methylmethane-sulphonate (Holway *et al.*, 2006), polycyclic aromatic hydrocarbons (Neher and Sturzenbaum, 2006), photosensitizers (Fujita *et al.*, 1984; Hartman and Marshall, 1992; Mills and Hartman, 1998), and prooxidant compounds (Astin *et al.*, 2008; Hartman *et al.*, 2004; Hyun *et al.*, 2008; Salinas *et al.*, 2006). Studies have taken advantage of the utility of *C. elegans* as an *in vivo* model; for example, it was shown that nucleotide excision repair slowed in aging individuals (Meyer *et al.*, 2007) and that longer lived and stress-resistant strains have faster nucleotide excision repair (Hyun *et al.*, 2008) than do wild type. It has been possible to identify cases in which UV resistance was correlated to life span (Hyun *et al.*, 2008; Murakami and Johnson, 1996), and others in which it was not (Hartman *et al.*, 1988), so that theories about the relationship of DNA damage and repair with aging can be directly tested. Studies of aging populations or individuals are slow and expensive in mammalian models and impossible *in vitro*.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 3096, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "5b998125-5827-43e5-84b9-f0f9844b8654": {"__data__": {"id_": "5b998125-5827-43e5-84b9-f0f9844b8654", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.11, para 4](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4e1e4616-4216-491b-b818-f3ff317439d6", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.11, para 4](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "8dfd6fdf7c8733002d511fe9355b89a7bbc681853d7b0ebe7ca6a92803e0c08b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "High-throughput screening has two specific definitions in toxicology: (1) genome-wide screens for molecular targets or mediators of toxicity and (2) rapid, high-content chemical screens to detect potential toxicants. A genome-wide screen can serve as a hypothesis-finding tool, providing a direction for further mechanistic investigation. This approach is particularly useful for studying any toxicant with a poorly understood mechanism of action. Genome-wide screens can be done using forward genetics, DNA microarrays, or genome-wide RNAi in *C. elegans*.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 557, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "08fd505a-566e-4718-904a-b093cab8641c": {"__data__": {"id_": "08fd505a-566e-4718-904a-b093cab8641c", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.11, para 5](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7cff36b5-6e8a-4ffe-a9c2-a058ad3ffc04", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.11, para 5](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "03fc7d28086716a8f102e1cb44bfbbf89643d17f72d3ebdecd8af5e61ff0da4d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "High-throughput chemical screening, in comparison, has been proposed as a quicker and less expensive method for toxicity testing (Gibb, 2008). The conventional animal testing used by companies or agencies is labor intensive and time consuming, resulting in a large number of toxicants not being tested at all. It is estimated, for instance, that there are more than 10,000 environmental chemicals from several Environmental Protection Agency programs that require further testing (Dix *et al.*, 2007). The objective of high-throughput chemical screening is to shortlist chemicals showing high toxicity, thereby setting priority for regulations as well as further toxicity testing in mammalian models.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 700, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "946d44ca-c91a-463b-86f9-3732917c65f0": {"__data__": {"id_": "946d44ca-c91a-463b-86f9-3732917c65f0", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.11, para 6](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "2a2f351e-cbe4-4e89-8e6f-3469ac595488", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.11, para 6](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "0620cb4046a68358cee32c19b087ac16bae6c803c8a0eb19856c3c6cd5555f79", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "High-throughput screening is feasible with *C. elegans* due to its experimental manipulability as well as several automation technologies. *Caenorhabditis elegans* is easy to handle in the laboratory; it can be cultivated on solid support or in liquid, in Petri dishes, tubes, or 6-, 12-, 24-, 96-, or 384-well plates. It can also be exposed to toxicants acutely or chronically by injection, feeding, or soaking. Automated imaging methods for absorbance, fluorescence, movement, or morphometric", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 494, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "236e5f9e-cfeb-43a1-a072-f414689ff156": {"__data__": {"id_": "236e5f9e-cfeb-43a1-a072-f414689ff156", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.12, para 0](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a1a58c5c-9dd5-4e7a-9f18-7eda10e9b2b3", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.12, para 0](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "1dabce1e264d57dc78bd3116332775cce00986a63de358ce4a741ae453768548", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "16                                                   LEUNG ET AL.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 65, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1d38c04e-dee3-4585-a1df-9c1a5e15de71": {"__data__": {"id_": "1d38c04e-dee3-4585-a1df-9c1a5e15de71", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.12, para 1](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "11f63118-2882-4ade-9742-c29c17a38468", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.12, para 1](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "bf1f93651459381633b4bb660830a55520d851260e8fe2fa19fff2d635edfea9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "measurement have been developed since the late 1980s (Baek *et al.*, 2002; Bennett and Pax, 1986; Hoshi and Shingai, 2006; Simonetta and Golombek, 2007; Tsibidis and Tavernarakis, 2007; Williams and Dusenbery, 1990b). Nowadays, cell sorters adapted to sort worms based on morphometric parameters or expression of fluorescent proteins combined with imaging platforms have been successfully used for large-scale promoter expression analyses and drug screening purposes (Burns *et al.*, 2006; Dupuy *et al.*, 2007; Pulak, 2006). Recently, a microfluidic *C. elegans* sorter with three dimensional subcellular imaging capabilities was developed, allowing high-throughput assays of higher complexity (Rohde *et al.*, 2007).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 718, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "ad168696-ca22-43a7-8f2b-7f7fa4d583b8": {"__data__": {"id_": "ad168696-ca22-43a7-8f2b-7f7fa4d583b8", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.12, para 2](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "bb2e4b4c-63a8-429a-8304-d2370d1c4fe6", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.12, para 2](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "5143d4d1858c1d07e3aa2557e88c1df4f9272b67b1328903f1119c251605943e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "While the simplicity and manipulability of the *C. elegans* system enables high-throughput approaches, it also leads to several potential disadvantages in toxicology studies. *Caenorhabditis elegans* exhibits important metabolic differences compared to vertebrates. For example, *C. elegans* is highly resistant to benzo\\[a]pyrene (Miller and Hartman, 1998), likely because it does not metabolize the chemical (M. Leung and J. Meyer, unpublished data). This problem can be potentially solved, however, by expressing the vertebrate cytochrome P450s in *C. elegans*. The impermeable cuticle layer as well as selective intestinal uptake, furthermore, may block the entry of chemicals, thereby necessitating high exposure doses to impact the worm\u2019s physiology. A mutant strain (*dal-1*) has recently been isolated that is healthy under laboratory conditions but exhibits altered intestinal morphology and increased intestinal absorption of a wide range of drugs (C. Paulson and J. Waddle, personal communication). The resultant-increased vulnerability of this strain to the toxic or pharmacological activities of tested compounds has the potential to increase the sensitivity of the *C. elegans* system.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1199, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8f386368-661a-4b17-826c-cf4afb5f8c3a": {"__data__": {"id_": "8f386368-661a-4b17-826c-cf4afb5f8c3a", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.12, para 3](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d30af8ce-5533-4d5d-a9b4-9a1242df1b1d", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.12, para 3](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "e5d2f7e40622ff4e63e776503685d210e3376bc09af00a2886bf5bdb5ba02133", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "epithelium in *C. elegans*. Such a tissue-specific mechanism would have been difficult to detect using *in vitro* cell cultures.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 128, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d0c136ba-39c9-4ef5-b065-d7aa0a117ebc": {"__data__": {"id_": "d0c136ba-39c9-4ef5-b065-d7aa0a117ebc", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.12, para 4](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "8d7b7d84-8690-4054-95c4-88fb3fc82382", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.12, para 4](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "dfcd5f51f0cc25763f37b94071602553b198c961170bbf2911060aee49451643", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Gene Expression Analysis in *C. elegans*", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 43, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3c1573fe-2536-41e9-be3e-fb2930630bec": {"__data__": {"id_": "3c1573fe-2536-41e9-be3e-fb2930630bec", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.12, para 5](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "cc6cc5c4-d63d-422d-8d95-f90da7e47739", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.12, para 5](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "4ad922da4f49633d8c65f0cf40e42f122f724e97e30a664e535539123a8fa492", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "*Caenorhabditis elegans* has several advantages over other species in gene expression analysis. WormBase (Harris *et al.*, 2004), the information-rich central genomic database of *C. elegans*, provides an intuitive interface into a well-annotated genome. *Caenorhabditis elegans* also has a consistent system of gene identification, thereby avoiding the confusion of gene identification that is common in many species, including human. The interactome modeling of *C. elegans* is also the most developed among all animal species (Dupuy *et al.*, 2007; Li *et al.* 2004, 2008; Zhong and Sternberg, 2006) and along with other genome-level bioinformatics tools (Kim *et al.*, 2001) greatly facilitates system-based analysis.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 721, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f8273786-b426-44f3-9a79-f2f6981d7859": {"__data__": {"id_": "f8273786-b426-44f3-9a79-f2f6981d7859", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.12, para 6](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "fd729972-186c-472d-8c9b-85052a3738b2", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.12, para 6](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "aa2a220aad57456aef9f91d811478f350dd7dc4392a06f4bee04ba2152fed4fe", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The results of gene expression analysis can be validated *in vivo* using mutational or transgenic approaches in *C. elegans*. For example, the gene expression of *C. elegans* exposed to ethanol, atrazine, polychlorinated biphenyls, endocrine disrupting chemicals, and polycyclic aromatic hydrocarbons have been profiled (Custodia *et al.*, 2001; Kwon *et al.*, 2004; Menzel *et al.*, 2007; Reichert and Menzel, 2005). Follow-up studies with transgenic *C. elegans* expressing fluorescent markers were used to detect overexpression of protein in specific tissues *in vivo* (Menzel *et al.*, 2007; Reichert and Menzel, 2005). Mutant *C. elegans* were also used to confirm the role of specific molecular targets based on gene expression analysis (Menzel *et al.*, 2007).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 767, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "74e53efd-7841-4cfe-9ccd-c59469605967": {"__data__": {"id_": "74e53efd-7841-4cfe-9ccd-c59469605967", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.12, para 7](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7a64e35d-1b17-4fd4-a656-97d63cf4899b", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.12, para 7](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "ccb11aa447a3c7650a3e309506eeb7dbdb6877b4fab93d72f9c08a7a0382c155", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Forward Genetics Screens in *C. elegans*", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 43, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8b9d991d-cc99-4814-82c5-e4f1c082828b": {"__data__": {"id_": "8b9d991d-cc99-4814-82c5-e4f1c082828b", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.12, para 8](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "b6318e75-bf27-4b32-8e9f-b50a3d312545", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.12, para 8](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "ca51b8ad406a6d051b23c8c99f1018a8b44df77e9356303333ae3b2ad7a32dba", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Forward genetics refers to the study of genes based on a given phenotype. In a forward genetics screen, *C. elegans* are treated with a mutagen, as described above. Mutant strains are then exposed to a toxicant and are screened for increased resistance or sensitivity. Once a resistant or hypersensitive mutant is identified, the mutation is located using two-point and three-point mapping and confirmed using single-gene rescue or RNAi phenocopying (Hodgkin and Hope, 1999). Forward genetics is efficient in *C. elegans* because the mutants can cover genes expressed in a variety of tissues. *Caenorhabditis elegans* is hermaphroditic, so homozygous mutant strains can be produced in the F2 generation via self-crossing.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 721, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "b606fd1a-9bb7-43a1-a323-d30d5cbdf4ad": {"__data__": {"id_": "b606fd1a-9bb7-43a1-a323-d30d5cbdf4ad", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.12, para 9](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "7d8ed56e-2a81-4b87-a702-21e8f667f5d6", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.12, para 9](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "ac51c1130764c4a38ae3fef56723cf4993a01c32f067f0b4d2656ddcd119a640", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Forward genetics screens are a useful method in mechanistic toxicology. Griffiths *et al.* (2001, 2005), for instance, discovered the role of glycolipid receptors and carbohydrate metabolism in *Bacillus thuringiensis* (Bt) toxins using *C. elegans* subjected to a forward genetics screen. The mutation of glycolipid receptors prevents Bt toxin from entering intestinal", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 369, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e4d046ba-d623-4f0c-85e3-abc71e80ebd3": {"__data__": {"id_": "e4d046ba-d623-4f0c-85e3-abc71e80ebd3", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.12, para 10](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "dda57e94-8e60-400f-b564-4bfa549c9db0", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.12, para 10](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "545a14918112ff978a115e9a9067d1ab3b87ae5f67e853ca5f190636e868e7e9", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Genome-Wide RNAi Screens in *C. elegans*", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 43, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "cc9e9bd8-f179-432d-a8d1-ecd4934ccb56": {"__data__": {"id_": "cc9e9bd8-f179-432d-a8d1-ecd4934ccb56", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.12, para 11](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "58f24c20-4091-4e5b-973f-8e3150652787", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.12, para 11](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "0d095dea60f4de95f85f6150a36f33b9a2a7926259b6013234dd41b3cee1bb87", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The discovery of RNAi mechanisms in *C. elegans* for which the 2006 Nobel Prize was awarded (Fire *et al.*, 1998) and the complete sequencing of the nematode genome (*C. elegans* Sequencing Consortium, 1998) led to the generation of publicly available RNAi libraries covering \\~90% of its genes (Fewell and Schmitt, 2006; Kamath and Ahringer, 2003). Strategies to improve RNAi efficiency, especially in neurons, were further developed (Esposito *et al.*, 2007; Lee *et al.*, 2006; Simmer *et al.* 2002, 2003; Tabara *et al.*, 2002; Tops *et al.*, 2005). RNAi can be triggered by injection of worms with interfering double-strand RNA (dsRNA), by feeding them with transgenic bacteria producing the dsRNA or by soaking them in a solution of dsRNA. The latter allow timed RNAi exposure and genome-wide screens in 96- or 384-well plates with liquid worm cultures and have contributed to discoveries of mechanisms of axon guidance as well as mitochondrial involvement in oxidative stress and aging (Ayyadevara *et al.*, 2007; Hamamichi *et al.*, 2008; Hamilton *et al.*, 2005; Ichishita *et al.*, 2008; Lee *et al.*, 2003; Schmitz *et al.*, 2007; Zhang *et al.*, 2006).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1164, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8aaf0e2e-94e6-4940-84e0-95499d5c48a8": {"__data__": {"id_": "8aaf0e2e-94e6-4940-84e0-95499d5c48a8", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.13, para 0](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f00e406a-b561-4b8e-b2ca-b67462279b91", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.13, para 0](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "dfa80e11838d842bc2f18624fd50b437f1e11b80252240b54e1923d0c22e646e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "CAENORHABDITIS ELEGANS IN TOXICOLOGY RESEARCH                                                                 17", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 112, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "d000a6ff-bca7-48ad-873c-62755f74f087": {"__data__": {"id_": "d000a6ff-bca7-48ad-873c-62755f74f087", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.13, para 1](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "a123cd46-95f0-4afb-8f45-64926798276f", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.13, para 1](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "a319a9d079fe887887643b0b343701a377a3de7945cbe7d9d6c24682b6ab7189", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "A genome-wide RNAi screen typically assesses a number of physiological parameters at the same time, such as viability, movement, food intake, and development, thereby facilitating the interpretation of screening results. While most RNAi screens have been done in wild-type *C. elegans*, some are performed using KO mutants to provide more sensitive or selective assays (Kaletta and Hengartner, 2006). Genome-wide RNAi screens are becoming a method of choice for discovering gene function. A recent study by Kim and Sun (2007), for example, identified a number of *daf-2*-dependent and nutrient-responsive genes that are responsive to paraquat-induced oxidative stress.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 668, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6e3ab778-c4e6-41bd-9c31-a803c7ea35bc": {"__data__": {"id_": "6e3ab778-c4e6-41bd-9c31-a803c7ea35bc", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.13, para 2](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "42753822-9a3b-4125-8990-091ad813095b", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.13, para 2](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "800b9a0a2629a39b9a8fb649922e796eae3879b3253352824382fb894d81246c", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "throughput screen to detect specific modes of action, including metal response (Cioci *et al.*, 2000), oxidative stress (Hasegawa *et al.*, 2008; Leiers *et al.*, 2003), and DNA damage (Denver *et al.*, 2006). A microfluidic *C. elegans* sorter with three-dimensional subcellular imaging capabilities was recently reported, thereby allowing high-throughput assays of higher complexity (Rohde *et al.*, 2007).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 408, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "88793846-897a-4192-a9ec-deec412f5423": {"__data__": {"id_": "88793846-897a-4192-a9ec-deec412f5423", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.13, para 3](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "5404960f-af36-4228-b4a0-31a71fd15473", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.13, para 3](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "12935824ebc0157ea8191a23c984c97e88b453c0d20a7e155d7edfa8aaa510c0", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## Environmental Assessment of Chemical Exposure", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 48, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "952cce10-ea35-416b-8607-4d6373ddf5f5": {"__data__": {"id_": "952cce10-ea35-416b-8607-4d6373ddf5f5", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.13, para 4](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "46211b31-a5a4-4ca0-8fa5-20498fa65abd", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.13, para 4](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "e908705759bf223cfa4558498df6d17fb0ae01cd861134b9d43e7d34c5c82cfc", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Nematodes are the most abundant animal in soil ecosystems and also found in aquatic and sediment environments. They serve many important roles in nutrient cycling and in maintaining environmental quality. These features have supported their use in ecotoxicological studies and, from the late 1970s, a variety of nematode species have been used to study environmental issues. During the late 1990s, *C. elegans* began to emerge as the nematode species of choice based on the tremendous body of knowledge developed by basic scientists using this model organism for biological studies. Although generally considered a soil organism, *C. elegans* lives in the interstitial water between soil particles and can be easily cultured within the laboratory in aquatic medium. The majority of environmental studies have been performed in an aquatic medium, given its ease of use, and as toxicological end points have been developed, the assessment tools have been applied to sediment and soil medium which allows for a more relevant direct environmental comparison.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1054, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "28503350-2100-4877-a340-44e217555131": {"__data__": {"id_": "28503350-2100-4877-a340-44e217555131", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.13, para 5](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3cc97c6b-12bf-4047-9730-9ee378196989", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.13, para 5](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "58923b5f11f4ca29f6899b24b7abccbb7466ba8340f51335ec707f12b8b807b7", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## High-Content Chemical Screens", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 32, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "c68a8255-ab1b-4b00-8bcc-6e1b42b4bb0b": {"__data__": {"id_": "c68a8255-ab1b-4b00-8bcc-6e1b42b4bb0b", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.13, para 6](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "3220a928-d342-401b-bc68-987fb711bebe", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.13, para 6](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "bb8c65f579b12f23becd28c976a7f800cd2f3d619b17810d7d698dee5b2d5dd3", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The use of *C. elegans* as a predictive model for human toxicity was first proposed in the context of heavy metals (Williams and Dusenbery, 1988). The *C. elegans* assay was validated as a predictor of mammalian acute lethality using eight different metal salts, generating LC50 values parallel to the rat and mouse LD50 values. A later study investigated the acute behavioral toxicity of 15 OP pesticides in *C. elegans* (Cole *et al.*, 2004). The toxicity of these pesticides in *C. elegans* was found to be significantly correlated to the LD50 acute lethality values in rats and mice. Several other studies have also validated a number of *C. elegans*-based assays for predicting neurological and developmental toxicity in mammalian species (Anderson *et al.*, 2004; Dhawan *et al.*, 1999; Tatara *et al.*, 1998; Williams *et al.*, 2000).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 841, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "2d71baba-381e-4c4e-b31e-f25656c7c595": {"__data__": {"id_": "2d71baba-381e-4c4e-b31e-f25656c7c595", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.13, para 7](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "021dbabf-11de-43bc-9967-7a92491c2d58", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.13, para 7](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "ea2b25adb1d6f66e6f6e7b7de72d9ffba78a54e4678d736ba75b45788dc8ff65", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "A *C. elegans*-based, high-throughput toxicity screen was first published by the Freedman group at National Institute of Environmental Health Sciences (Peterson *et al.*, in press); additional groups including industry and government groups in the United States and elsewhere are also carrying out high-throughput toxicity screening. Screens are typically conducted on a 96-well plate with a robotic liquid handling workstation (Biosort, Union Biometrica, Inc., Holliston, MA) to analyze the length, optical density, motion, and fluorescence of *C. elegans*. *Caenorhabditis elegans* is cultured in liquid from fertilized egg to adult through four distinct larval stages. The development, reproduction, and feeding behaviors of the *C. elegans* culture in response to different chemical exposures are characterized. The screen has been validated by the Freedman group with 60 chemicals including metals, pesticides, mutagens, and nontoxic agents (Peterson *et al.*, in press).", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 976, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8410644b-dd57-4af6-8cbc-6b173085514b": {"__data__": {"id_": "8410644b-dd57-4af6-8cbc-6b173085514b", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.13, para 8](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "07b1406c-5318-48ad-b761-96fba717b0e5", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.13, para 8](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "4169583023492126c49d8abf216f5be9d2e6fbf4375560939f110c246184833f", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The high-throughput toxicity screen is being further improved with additional genetics and automation techniques. The generalized stress response of *C. elegans*, for instance, was visualized with transgenic GFP constructs, providing a more sensitive end point for toxicity screens (Dengg and van Meel, 2004; Roh *et al.*, 2006). Nematode locomotion can be tracked automatically, providing a more sensitive screen of neurotoxicity (Cole *et al.*, 2004; Williams and Dusenbery, 1990b). Transgenic or mutant *C. elegans* can also be used in the high-", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 548, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "1c6d67df-3e69-4ad9-a4a0-4afc2aef72e3": {"__data__": {"id_": "1c6d67df-3e69-4ad9-a4a0-4afc2aef72e3", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.13, para 9](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1f05262b-7cd7-4255-afa4-908b6aeaec01", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.13, para 9](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "03bd559dd2342b6db8524955d42c1c1aa4e9b54b6bc016820350918571040248", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The environmental toxicological literature using *C. elegans* is extensive and Table 6 provides an overview of laboratory-based studies where a toxicant of environmental interest has been added to a medium (water, sediment, or soil) followed by exposure to *C. elegans* and the assessment of an adverse effect. In a limited number of situations, *C. elegans* testing has been used to assess contamination in field settings (Table 7). Much of the early work explored metal toxicity and used lethality as an endpoint. Over time, a wider variety of toxicants have been tested and more sophisticated sublethal end points have been developed including the use of transgenic strains with specific biomarkers (Candido and Jones, 1996; Chu *et al.*, 2005; Dengg and van Meel, 2004; Easton *et al.*, 2001; Mutwakil *et al.*, 1997; Roh *et al.*, 2006), growth and reproduction (Anderson *et al.*, 2001; Hoss and Weltje, 2007), feeding (Boyd *et al.*, 2003), and movement (Anderson *et al.*, 2004). These types of end points developed through environmental studies are directly applicable to the use of the organism as an alternative for mammalian testing.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1145, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "0eabf8f1-ba33-491e-b983-58222f7e88ad": {"__data__": {"id_": "0eabf8f1-ba33-491e-b983-58222f7e88ad", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.13, para 10](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "62cd659b-0771-4a0f-8669-4c71258cff6a", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.13, para 10](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "2df2193cfb7595393a8f375f5b442d02f64e3693793805a8d75433a838f01e20", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Two of the principal limitations in using *C. elegans* in environmental testing are concerns related to its comparison to other nematodes and reliable and simple methods for extracting them from soil and sediments. Given the almost countless variety of nematodes, it is impossible for one species to be representative of the entire Nematoda phylum. Limited studies", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 364, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "514c3cca-f90b-47c7-a841-6eea3e865200": {"__data__": {"id_": "514c3cca-f90b-47c7-a841-6eea3e865200", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.14, para 0](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "87db9b85-2930-49d2-b05d-c7667a75b1dd", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.14, para 0](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "71f01c7e49a58128b08505a39546bd759bd3c874d12f3205e5aea6f2f3bbb693", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "18                                                                                   LEUNG ET AL.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 97, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "669b2639-b119-4a51-bcd3-171aab18e621": {"__data__": {"id_": "669b2639-b119-4a51-bcd3-171aab18e621", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.14, para 1](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "aec61bfe-4b15-421f-852b-cf5ab75f38e4", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.14, para 1](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "3e7f9885c3ac56b1a1cb94cf2866479c57a03f628d8d3afacde6dd2f631b0871", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "```\n                                                                                   TABLE 6\n                                               Representative Laboratory Studies Evaluating Environmentally Relevant Toxicants\n```", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 225, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "bfb3a1e8-67bc-4130-a57e-4ac481116075": {"__data__": {"id_": "bfb3a1e8-67bc-4130-a57e-4ac481116075", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.14, para 2](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "c01221e7-0dc8-4a01-99bc-1646a7feb6aa", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.14, para 2](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "b8af42d515aef08173b0db82a6cab3ac5ff83e60378ba064de13aaaafb756875", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Medium|End point (test duration)|Chemicals tested/comments|References|\n|-|-|-|-|\n|A. Aquatic|Lethality (24\u201396 h)|Tested metallic salts of 14 metals (Ag, Hg, Be, Al, Cu, Zn, Pb, Cd, Sr, Cr, As, Tl, Ni, Sb). Established initial aquatic testing procedures and compared results to traditionally used aquatic invertebrates.|Williams and Dusenbery (1990a)|\n||Lethality and stress reporter gene induction (8\u201396 h)|Assessed the induction of \\*hsp16-lacZ\\* and lethality in \\*C. elegans\\* exposed to water-soluble salts of Cd, Cu, Hg, As, and Pb.|Stringham and Candido 1994|\n||Growth, behavior, feeding, and reproduction (4\u201372 h)|Compared a number of sublethal end points and found feeding and behavior to be the most sensitive. Tested metallic salts Cd, Cu, and Pb.|Anderson \\*et al.\\* (2001)|\n||Feeding and movement (4\u201324 h)|Determined changes in ingestion using microbeads and movement in the presence of metals and varying availability of food|Boyd \\*et al.\\* (2003)|\n||Behavior (4 h)|Tested a variety of toxicants from several categories of chemicals including metals, pesticides, and organic solvents. Established the use of a 4-h exposure period for behavioral assessments.|Anderson \\*et al.\\* (2004)|\n|B. Sediment|Reproduction (96 h)|Evaluated the effects on reproduction of several endocrine disruptors.|Hoss and Weltje (2007)|\n||Growth (72 h)|CuSO\\4\\ in spiked water added to whole sediments and refined method for using organism in sediments.|Hoss \\*et al.\\* (1997)|\n||Growth (72 h)|Spiked natural sediments with CdCl\\2\\ and extracted pore water to determine effects.|Hoss \\*et al.\\* (2001)|\n|C. Soil|Lethality (24 h)|Spiked soil with CuCl\\2\\ and developed the recovery method used with \\*C. elegans\\* exposed in soil.|Donkin and Dusenberry (1993)|\n||Lethality (24 h)|Tested metallic salts of five metals (Cu, Cd, Zn, Pb, Ni) in artificial soil. Compared \\*C. elegans\\* data to earthworm data from same medium. Determined that 24-h exposures for the nematode had similar effects to 14-day exposures with earthworms.|Peredney and Williams (2000)|\n||Lethality (24\u201348 h)|Tested seven organic pollutants (four azarenes, one short-chain chlorinated paraffin, and two organochlorinated pesticides) in soil, aquatic, and agar and compared results across media.|Sochova \\*et al.\\* (2007)|\n> comparing the toxicological effects between nematodes species indicate that *C. elegans* is as representative as any of the ones commonly used and, in many cases, little difference in response has been found between species (Boyd and Williams, 2003; Kammenga *et al.*, 2000). Further, this organism is much more thoroughly understood and benefits from its ease of use.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 2654, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "20f99f6e-0b24-4686-b1e0-d60ce37665c4": {"__data__": {"id_": "20f99f6e-0b24-4686-b1e0-d60ce37665c4", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.14, para 3](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6f810a1e-5c90-4fc7-a0cb-4ba61086f7fe", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.14, para 3](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "8b55ab70df67d419d6dcce39f7d2fd6e81579dcbc8ce76a4d0a9689eba58f57d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "```\n                                                                                   TABLE 7\n                                                         Examples of Field Studies Using *Caenorhabditis elegans* to Assess Environmental Samples\n```", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 244, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "202ce6e6-3c08-4af9-9331-a8b0eb6d8b4a": {"__data__": {"id_": "202ce6e6-3c08-4af9-9331-a8b0eb6d8b4a", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.14, para 4](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6b8ed7da-16fc-4c2d-8f9e-c33e57b93f6e", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.14, para 4](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "53f4936593bd697eb9c6cb8c11c1b88adfe95fa9a1be11be8415b39b5a2f4f47", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "|Field site|Environmental medium|Overview|References|\n|-|-|-|-|\n|Carnon River system (England)|Water|Transgenic strains of \\*C. elegans\\* that carry stress-inducible \\*lacZ\\* reporter genes were used to assess metal contamination of a river system.|Mutwakil \\*et al.\\* (1997)|\n|Wastewater treatment process (Georgia)|Water discharges from industrial operations and a municipal treatment plant|The contribution of several industrial operations to the waste stream feeding a municipal wastewater treatment plant and the treatment plant\u2019s discharge were assessed to identify sources of water contamination and effectiveness of waste treatment. The 72-h mortality was used as end point.|Hitchcock \\*et al.\\* (1997)|\n|Elbe River (Germany)|Sediments|Tested polluted sediments using growth and fertility as end points.|Traunspurger \\*et al.\\* (1997)|\n|Twelve freshwater lakes (Germany)|Fresh water sediment|Evaluated 26 sediment samples from unpolluted lakes in southern Germany to determine the effect of sediment size and organic content on growth and fertility.|Hoss \\*et al.\\* (1999)|\n|Middle Tisza River flood plain (Hungary)|Soil|Following a major release of cyanide and heavy metals from a mine waste lagoon in Romania, soil contamination was assessed following a 100-year flood event using mortality as end point.|Black and Williams (2001)|\n|Agricultural soil (Germany)|Soil|Assessed the toxicity of soil from fields cultivated with transgenic corn (\\*Bt\\* corn; MON810) compared to isogenic corn. Growth and reproduction used as end points.|Hoss \\*et al.\\* (2008)|", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 1566, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "307fb1ef-d652-4299-b6ec-2cec0bd54667": {"__data__": {"id_": "307fb1ef-d652-4299-b6ec-2cec0bd54667", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.15, para 0](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "4ce56cd8-7807-4dce-b326-d8a66af8e855", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.15, para 0](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "e67015b4ce9ca15d0a754bae019cda7ecf273a9399dd81d049afa854eb10b93d", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "# CAENORHABDITIS ELEGANS IN TOXICOLOGY RESEARCH", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 47, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "f49ab0b3-e923-4dbf-98df-8e1d10a43193": {"__data__": {"id_": "f49ab0b3-e923-4dbf-98df-8e1d10a43193", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.15, para 1](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "6d289ec3-56dc-46d3-975f-85eff551cc05", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.15, para 1](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "d965ecf32bc09411d78631b1bec99143f51fa3f010b508dd5cbea23a5a1afd1b", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Much progress has been made to develop better methods to extract the worm from soil and sediments. The initial method developed by Donkin and Dusenbery (1993) has led to a standardized soil toxicological testing method adopted in 2001 by the American Society for Testing and Materials (ASTM, 2002) and recently the International Standards Organization in Europe (ISO 2007). The initial extraction method has been improved through the use of transgenic strains of nematodes (Graves *et al.*, 2005) which allows for GFP-labeled worms to be used that distinguishes the worms being tested in soils from the large numbers of indigenous species that are similar in size and appearance. It also makes easier removal from soil with high organic content. All this work has led to more interest in using *C. elegans* in environmental studies.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 832, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6aa08196-650b-40c3-8aa4-9045aafe9ca2": {"__data__": {"id_": "6aa08196-650b-40c3-8aa4-9045aafe9ca2", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.15, para 2](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "f4655291-22fa-4f25-b548-e67bf8efdb35", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.15, para 2](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "c6a2f3ec00b793063303d2b8da9f582c7cd0a9f19cc092cf431483814315de8e", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## CONCLUSION: THE ROLE OF *C. elegans* IN TOXICOLOGY RESEARCH", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 62, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "8341ae0c-3a16-446c-a071-a563743d4a3d": {"__data__": {"id_": "8341ae0c-3a16-446c-a071-a563743d4a3d", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.15, para 3](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d6f88844-5aa4-44db-ae6b-678bf91e4678", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.15, para 3](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "88dcdc6588356cde5cd8ff8eb0308385ea4142a96bfaefe6f0166afefd6bd508", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "The unique features of *C. elegans* make it an excellent model to complement mammalian models in toxicology research. Experiments with *C. elegans* do not incur the same costs as experiments with *in vivo* vertebrate models, while still permitting testing of hypotheses in an intact metazoan organism. The genetic tools available for *C. elegans* make it an excellent model for studying the roles of specific genes in toxicological processes and gene-environment interactions, while the life history of this organism lends itself to high-throughput analyses. Thus, *C. elegans* represents an excellent complement to *in vitro* or cell culture\u2013based systems and *in vivo* vertebrate models.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 689, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "fe0f6c30-01a4-43de-a908-f3cf74f452bd": {"__data__": {"id_": "fe0f6c30-01a4-43de-a908-f3cf74f452bd", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.15, para 4](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "43066c0a-fc5e-4bc6-8920-bbf29c9b06a1", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.15, para 4](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "27d1718c3bc543973676b8cc3013a7e9c43206828ee31db4ed6981900a1588d5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## FUNDING", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 10, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "479f7c5d-4162-4607-af8f-3eb2e4c9761e": {"__data__": {"id_": "479f7c5d-4162-4607-af8f-3eb2e4c9761e", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.15, para 5](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d2be2d8d-7eff-45a8-b156-3b9550258a55", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.15, para 5](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "300790228265ae002f8bb6ae5edd1ad354931cf364167e4ac58ab084b5eec0ac", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "National Institute of Environmental Health Sciences 10563; Department of Defense W81XWH-05-1-0239; the Gray E.B. Stahlman Chair of Neuroscience.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 144, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "e43a4b4c-f284-4ed5-ae20-86901588d35f": {"__data__": {"id_": "e43a4b4c-f284-4ed5-ae20-86901588d35f", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.15, para 6](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "1b5a1035-c876-4c3a-bc67-58cb346abf79", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.15, para 6](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "3d5f4dd0e6e7aef9cc5667b65d168937ba07ac583eafddf4d78db8c2097168e5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## ACKNOWLEDGMENTS", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 18, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6fadd8ac-9574-43e2-b7af-6bfce780dc22": {"__data__": {"id_": "6fadd8ac-9574-43e2-b7af-6bfce780dc22", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.15, para 7](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ec2a5050-a7c2-4285-8f7f-b0ced90dbabe", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.15, para 7](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "38b36c539ea06082b254b53da8818933f5f3b69e8835e14058acd4e5a23d6284", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "We thank Windy A. Boyd, Richard T. Di Giulio, and Jonathan H. Freedman for advice and assistance in the preparation of the manuscript.", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 134, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "6e35f1cb-87cc-4c78-8bb4-21267a4c3321": {"__data__": {"id_": "6e35f1cb-87cc-4c78-8bb4-21267a4c3321", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.15, para 8](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "ea1ab8ec-9dd2-49de-9292-84b77073cb57", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.15, para 8](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "76f5cb9e8732d63c33db7b7388ad9eada4631aece543129736e6640cef4db0a5", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "## REFERENCES", "mimetype": "text/plain", "start_char_idx": 0, "end_char_idx": 13, "text_template": "{metadata_str}\n\n{content}", "class_name": "TextNode"}, "__type__": "1"}, "3eb7f5e9-ca45-4703-bb6e-d40e129bf459": {"__data__": {"id_": "3eb7f5e9-ca45-4703-bb6e-d40e129bf459", "embedding": null, "metadata": {"source document": "Publication: [kfn121, p.15, para 9](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "excluded_embed_metadata_keys": [], "excluded_llm_metadata_keys": [], "relationships": {"1": {"node_id": "d2a4d6da-7ed6-4d39-a35c-2bdcb43e7cfa", "node_type": "4", "metadata": {"source document": "Publication: [kfn121, p.15, para 9](https://pubmed.ncbi.nlm.nih.gov/18566021/)"}, "hash": "4786a2984d593b593b4729489c5225f988fc5e573fd153ff80426c5142ce7b0a", "class_name": "RelatedNodeInfo"}}, "metadata_template": "{key}: {value}", "metadata_separator": "\n", "text": "Ahmed, S. (2006). 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