{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T13:26:30Z","timestamp":1790169990341,"version":"4.1.0"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T00:00:00Z","timestamp":1734393600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIHD","award":["P30HD071593"],"award-info":[{"award-number":["P30HD071593"]}]},{"DOI":"10.13039\/100000025","name":"NIMH","doi-asserted-by":"crossref","award":["R01MH112689"],"award-info":[{"award-number":["R01MH112689"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000057","name":"NIGMS","doi-asserted-by":"crossref","award":["R01GM066897"],"award-info":[{"award-number":["R01GM066897"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosbiology.org"],"crossmark-restriction":false},"short-container-title":["PLoS Biol"],"abstract":"<jats:p>Despite decades of research on the <jats:italic>Caenorhabditis elegans<\/jats:italic> nervous system based on an anatomical description of synaptic connectivity, the circuits underlying behavior remain incompletely described and the functions of many neurons are still unknown. Updated and more complete chemical and gap junction connectomes of both adult sexes covering the entire animal including the muscle end organ have become available recently. Here, these are analyzed to gain insight into the overall structure of the connectivity network and to suggest functions of individual neuron classes. Modularity analysis divides the connectome graph into 10 communities that can be correlated with broad categories of behavior. A significant role of the body wall musculature end organ is emphasized as both a site of significant information convergence and as a source of sensory input in a feedback loop. Convergence of pathways for multisensory integration occurs throughout the network\u2014most interneurons have similar indegrees and outdegrees and hence disperse information as much as they aggregate it. New insights include description of a set of high degree interneurons connected by many gap junctions running through the ventral cord that may represent a previously unrecognized locus of information processing. There is an apparent mechanosensory and proprioceptive field covering the entire body formed by connectivity of the many mechanosensory neurons of multiple types to 2 interneurons with output connections across the nervous system. Several additional significant, previously unrecognized circuits and pathways are uncovered, some involving unstudied neurons. The insights are valuable for guiding theoretical investigation of network properties as well as experimental studies of the functions of individual neurons, groups of neurons, and circuits.<\/jats:p>","DOI":"10.1371\/journal.pbio.3002939","type":"journal-article","created":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T18:22:08Z","timestamp":1734459728000},"page":"e3002939","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["Comprehensive analysis of the C. elegans connectome reveals novel circuits and functions of previously unstudied neurons"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6511-9972","authenticated-orcid":true,"given":"Scott W.","family":"Emmons","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,12,17]]},"reference":[{"key":"pbio.3002939.ref001","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1098\/rstb.1986.0056","article-title":"The structure of the nervous system of the nematode Caenorhabditis elegans","volume":"314","author":"JG White","year":"1986","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"issue":"7986","key":"pbio.3002939.ref002","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1038\/s41586-023-06683-4","article-title":"Neural signal propagation atlas of Caenorhabditis elegans","volume":"623","author":"F Randi","year":"2023","journal-title":"Nature"},{"issue":"22","key":"pbio.3002939.ref003","doi-asserted-by":"crossref","first-page":"3570","DOI":"10.1016\/j.neuron.2023.09.043","article-title":"The neuropeptidergic connectome of C. elegans","volume":"111","author":"L Ripoll-S\u00e1nchez","year":"2023","journal-title":"Neuron"},{"issue":"7763","key":"pbio.3002939.ref004","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/s41586-019-1352-7","article-title":"Whole-animal connectomes of both Caenorhabditis elegans sexes","volume":"571","author":"SJ Cook","year":"2019","journal-title":"Nature"},{"issue":"7871","key":"pbio.3002939.ref005","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1038\/s41586-021-03778-8","article-title":"Connectomes across development reveal principles of brain maturation","volume":"596","author":"D Witvliet","year":"2021","journal-title":"Nature"},{"issue":"5","key":"pbio.3002939.ref006","doi-asserted-by":"crossref","first-page":"e1001139","DOI":"10.1371\/journal.pcbi.1001139","article-title":"Topological cluster analysis reveals the systemic organization of the Caenorhabditis elegans connectome.","volume":"7","author":"Y Sohn","year":"2011","journal-title":"PLoS Comput Biol"},{"key":"pbio.3002939.ref007","doi-asserted-by":"crossref","first-page":"e1001066","DOI":"10.1371\/journal.pcbi.1001066","article-title":"Structural properties of the Caenorhabditis elegans neuronal network.","volume":"7","author":"LR Varshney","year":"2011","journal-title":"PLoS Comput Biol"},{"issue":"15","key":"pbio.3002939.ref008","doi-asserted-by":"crossref","first-page":"6380","DOI":"10.1523\/JNEUROSCI.3784-12.2013","article-title":"The rich club of the C. elegans neuronal connectome","volume":"33","author":"EK Towlson","year":"2013","journal-title":"J Neurosci"},{"issue":"2","key":"pbio.3002939.ref009","doi-asserted-by":"crossref","first-page":"e9240","DOI":"10.1371\/journal.pone.0009240","article-title":"Mesoscopic organization reveals the constraints governing Caenorhabditis elegans nervous system.","volume":"5","author":"RK Pan","year":"2010","journal-title":"PLoS ONE"},{"issue":"8","key":"pbio.3002939.ref010","doi-asserted-by":"crossref","first-page":"e1005084","DOI":"10.1371\/journal.pcbi.1005084","article-title":"Vulnerability-based critical neurons, synapses, and pathways in the Caenorhabditis elegans connectome.","volume":"12","author":"S Kim","year":"2016","journal-title":"PLoS Comput Biol"},{"issue":"11","key":"pbio.3002939.ref011","doi-asserted-by":"crossref","first-page":"118703","DOI":"10.1103\/PhysRevLett.100.118703","article-title":"Community structure in directed networks","volume":"100","author":"EA Leicht","year":"2008","journal-title":"Phys Rev Lett"},{"issue":"16","key":"pbio.3002939.ref012","doi-asserted-by":"crossref","first-page":"3443","DOI":"10.1016\/j.cub.2022.06.039","article-title":"A set of hub neurons and non-local connectivity features support global brain dynamics in C. elegans","volume":"32","author":"K Uzel","year":"2022","journal-title":"Curr Biol"},{"issue":"1758","key":"pbio.3002939.ref013","doi-asserted-by":"crossref","first-page":"20170371","DOI":"10.1098\/rstb.2017.0371","article-title":"Sensorimotor integration in Caenorhabditis elegans: a reappraisal towards dynamic and distributed computations","volume":"373","author":"HS Kaplan","year":"2018","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"issue":"6552","key":"pbio.3002939.ref014","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1038\/378082a0","article-title":"Synaptic code for sensory modalities revealed by C. elegans GLR-1 glutamate receptor","volume":"378","author":"AC Hart","year":"1995","journal-title":"Nature"},{"key":"pbio.3002939.ref015","doi-asserted-by":"crossref","first-page":"3184","DOI":"10.1073\/pnas.0409009101","article-title":"A circuit for navigation in Caenorhabditis elegans","volume":"102","author":"JM Gray","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pbio.3002939.ref016","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1038\/nature04538","article-title":"A C. elegans stretch receptor neuron revealed by a mechanosensitive TRP channel homologue","volume":"440","author":"W Li","year":"2006","journal-title":"Nature"},{"key":"pbio.3002939.ref017","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1523\/JNEUROSCI.11-01-00001.1991","article-title":"The posterior nervous system of the nematode Caenorhabditis elegans: Serial reconstruction of identified neurons and complete pattern of synaptic interactions","volume":"11","author":"DH Hall","year":"1991","journal-title":"J Neurosci"},{"key":"pbio.3002939.ref018","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1523\/JNEUROSCI.05-04-00956.1985","article-title":"The neural circuit for touch sensitivity in Caenorhabditis elegans","volume":"5","author":"M Chalfie","year":"1985","journal-title":"J Neurosci"},{"issue":"6","key":"pbio.3002939.ref019","doi-asserted-by":"crossref","first-page":"e1003618","DOI":"10.1371\/journal.pgen.1003618","article-title":"Neuronal target identification requires AHA-1-mediated fine-tuning of Wnt signaling in C. elegans.","volume":"9","author":"J Zhang","year":"2013","journal-title":"PLoS Genet"},{"issue":"6910","key":"pbio.3002939.ref020","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1038\/nature01170","article-title":"Antagonistic pathways in neurons exposed to body fluid regulate social feeding in Caenorhabditis elegans","volume":"419","author":"JC Coates","year":"2002","journal-title":"Nature"},{"key":"pbio.3002939.ref021","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1002\/neu.10014","article-title":"Serotonin modulates locomotory behavior and coordinates egg-laying and movement in Caenorhabditis elegans","volume":"49","author":"LA Hardaker","year":"2001","journal-title":"J Neurobiol"},{"key":"pbio.3002939.ref022","volume-title":"Studies on the development and organization of the nervous system of Caenorhabditis elegans.","author":"RM Durbin","year":"1987"},{"key":"pbio.3002939.ref023","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1126\/science.1221762","article-title":"The connectome of a decision-making neural network","volume":"337","author":"TA Jarrell","year":"2012","journal-title":"Science"},{"key":"pbio.3002939.ref024","doi-asserted-by":"crossref","first-page":"e29257","DOI":"10.7554\/eLife.29257","article-title":"Multiple conserved cell adhesion protein interactions mediate neural wiring of a sensory circuit in C","volume":"6","author":"B Kim","year":"2017","journal-title":"elegans. eLife"},{"key":"pbio.3002939.ref025","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1146\/annurev-neuro-070918-050314","article-title":"Glia-neuron interactions in Caenorhabditis elegans","volume":"42","author":"A Singhvi","year":"2019","journal-title":"Annu Rev Neurosci"},{"issue":"1","key":"pbio.3002939.ref026","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0896-6273(00)80021-5","article-title":"Neuroglia and Pioneer Neurons Express UNC-6 to Provide Global and Local Netrin Cues for Guiding Migrations in C. elegans","volume":"16","author":"WG Wadsworth","year":"1996","journal-title":"Neuron"},{"issue":"9","key":"pbio.3002939.ref027","doi-asserted-by":"crossref","first-page":"e3002280","DOI":"10.1371\/journal.pbio.3002280","article-title":"Inhibitory feedback from the motor circuit gates mechanosensory processing in Caenorhabditis elegans","volume":"21","author":"S Kumar","year":"2023","journal-title":"PLoS Biol"},{"issue":"6435","key":"pbio.3002939.ref028","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/364337a0","article-title":"The GABAergic nervous system of Caenorhabditis elegans","volume":"364","author":"SL Mclntire","year":"1993","journal-title":"Nature"},{"issue":"2","key":"pbio.3002939.ref029","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/0012-1606(80)90352-8","article-title":"The Caenorhabditis elegans male: postembryonic development of nongonadal structures","volume":"78","author":"JE Sulston","year":"1980","journal-title":"Dev Biol"},{"issue":"10","key":"pbio.3002939.ref030","doi-asserted-by":"crossref","first-page":"R405","DOI":"10.1016\/j.cub.2015.03.043","article-title":"Cross-referencing online activity with the connectome to identify a neglected but well-connected neuron","volume":"25","author":"EL Ardiel","year":"2015","journal-title":"Curr Biol"},{"issue":"5","key":"pbio.3002939.ref031","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/j.cell.2013.08.001","article-title":"Serotonin and the neuropeptide PDF initiate and extend opposing behavioral states in C. elegans","volume":"154","author":"SW Flavell","year":"2013","journal-title":"Cell"},{"key":"pbio.3002939.ref032","first-page":"2022.09.19.508547","article-title":"A neuron that regulates locomotion makes a potential sensory cilium lying over the C. elegans egg-laying apparatus","author":"NTM Christie","year":"2022","journal-title":"bioRxiv [Preprint]."},{"issue":"16","key":"pbio.3002939.ref033","doi-asserted-by":"crossref","first-page":"2437","DOI":"10.1038\/emboj.2009.194","article-title":"Dopamine counteracts octopamine signalling in a neural circuit mediating food response in C. elegans","volume":"28","author":"S Suo","year":"2009","journal-title":"EMBO J"},{"issue":"23","key":"pbio.3002939.ref034","doi-asserted-by":"crossref","first-page":"4108","DOI":"10.1016\/j.cub.2019.10.012","article-title":"Coordinated behavioral and physiological responses to a social signal are regulated by a shared neuronal circuit","volume":"29","author":"EZ Aprison","year":"2019","journal-title":"Curr Biol"},{"issue":"12","key":"pbio.3002939.ref035","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1038\/nn.3253","article-title":"PDF-1 neuropeptide signaling modulates a neural circuit for mate-searching behavior in C. elegans","volume":"15","author":"A Barrios","year":"2012","journal-title":"Nat Neurosci"},{"key":"pbio.3002939.ref036","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1126\/science.1226201","article-title":"Oxytocin\/vasopressin-related peptides have an ancient role in reproductive behavior","volume":"338","author":"JL Garrison","year":"2012","journal-title":"Science"},{"issue":"43","key":"pbio.3002939.ref037","doi-asserted-by":"crossref","first-page":"14571","DOI":"10.1523\/JNEUROSCI.1369-15.2015","article-title":"Distinct mechanisms underlie quiescence during two Caenorhabditis elegans sleep-like states","volume":"35","author":"NF Trojanowski","year":"2015","journal-title":"J Neurosci"},{"key":"pbio.3002939.ref038","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1038\/nature07886","article-title":"A hub-and-spoke circuit drives pheromone attraction and social behavior in C. elegans","volume":"458","author":"EZ Macosko","year":"2009","journal-title":"Nature"},{"issue":"19","key":"pbio.3002939.ref039","doi-asserted-by":"crossref","first-page":"4134","DOI":"10.1016\/j.cell.2023.07.035","article-title":"Brain-wide representations of behavior spanning multiple timescales and states in C. elegans","volume":"186","author":"AA Atanas","year":"2023","journal-title":"Cell"},{"issue":"20","key":"pbio.3002939.ref040","doi-asserted-by":"crossref","first-page":"5122","DOI":"10.1016\/j.cell.2021.08.024","article-title":"Natural sensory context drives diverse brain-wide activity during C. elegans mating","volume":"184","author":"V Susoy","year":"2021","journal-title":"Cell"},{"issue":"4","key":"pbio.3002939.ref041","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/j.neuron.2012.08.039","article-title":"Proprioceptive coupling within motor neurons drives C. elegans forward locomotion","volume":"76","author":"Q Wen","year":"2012","journal-title":"Neuron"},{"key":"pbio.3002939.ref042","volume-title":"Role of the SAA and SMB neurons in locomotion in the nematode Caenorhabditis elegans, with a focus on steering","author":"E. Kalogeropoulou","year":"2018"},{"key":"pbio.3002939.ref043","article-title":"The putative chemoreceptor families of C.elegans (January 06, 2006).","author":"HM Robertson","year":"2006","journal-title":"WormBook;"},{"key":"pbio.3002939.ref044","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.conb.2017.01.005","article-title":"Multisensory integration in C. elegans","volume":"43","author":"DD Ghosh","year":"2017","journal-title":"Curr Opin Neurobiol"},{"issue":"1758","key":"pbio.3002939.ref045","doi-asserted-by":"crossref","first-page":"20170367","DOI":"10.1098\/rstb.2017.0367","article-title":"Clues to basis of exploratory behaviour of the C. elegans snout from head somatotropy","volume":"373","author":"J. White","year":"2018","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"issue":"5555","key":"pbio.3002939.ref046","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1126\/science.1066642","article-title":"Immunoglobulin-domain proteins required for maintenance of ventral nerve cord organization","volume":"295","author":"O Aurelio","year":"2002","journal-title":"Science"}],"container-title":["PLOS Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pbio.3002939","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T18:22:30Z","timestamp":1734459750000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pbio.3002939"}},"subtitle":[],"editor":[{"given":"Mark J.","family":"Alkema","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,12,17]]},"references-count":46,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12,17]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pbio.3002939","relation":{},"ISSN":["1545-7885"],"issn-type":[{"value":"1545-7885","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,17]]}}}