{"doi":"10.1101/2025.09.12.675944","title":"Connectome simulations identify a central pattern generator circuit for fly walking","abstract":"<jats:title>Abstract</jats:title>\n                <jats:p>\n                  Animal locomotion relies on rhythmic body movements driven by central pattern generators (CPGs): neural circuits that produce oscillating output without oscillating input. However, the circuit structure of a CPG for walking is not known in any animal. To identify the cells and synapses that underlie rhythmic leg movement in walking flies, we developed dynamic simulations of the\n                  <jats:italic>Drosophila</jats:italic>\n                  ventral nerve cord (VNC) connectomes. A computational activation screen of descending neurons from the central brain identified DNg100—a known command neuron for walking—as the top driver of rhythmic leg motor activity. Simulated network pruning isolated a minimal rhythm-generating circuit consisting of one inhibitory and two excitatory interneurons; this three-neuron circuit was necessary and sufficient for motor rhythms across all six legs and in four connectome datasets. Simulations also predicted that a separate descending pathway (DNb08) drives rhythmic leg movements, which we confirmed experimentally using optogenetics in behaving flies. Our results reveal the cellular identity and synaptic structure of a putative CPG circuit for walking and other rhythmic leg movements in flies.\n                </jats:p>","journal":null,"year":null,"id":647700,"datarank":0.42819406750058214,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"self_citation_contribution":0.38474240361923057,"citation_network_contribution":0.04345166388135156,"self_endowment_contribution":0.38474240361923057,"citer_contribution":0.04345166388135156,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":5,"citers_with_citation_signal":3,"citers_with_endowment":3,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1160051,"name":"Grant M Chou","orcid":"0009-0001-3003-2631","position":1,"is_corresponding":false},{"id":254953,"name":"Elliott T. T. Abe","orcid":"0000-0002-5305-2467","position":2,"is_corresponding":false},{"id":1426445,"name":"Denis Turcu","orcid":"0000-0002-2955-2568","position":3,"is_corresponding":false},{"id":1687629,"name":"Jackson K. Lancaster","orcid":null,"position":4,"is_corresponding":false},{"id":285978,"name":"John C Tuthill","orcid":"0000-0002-5689-5806","position":5,"is_corresponding":false},{"id":268636,"name":"Bingni W. Brunton","orcid":"0000-0002-4831-3466","position":6,"is_corresponding":false},{"id":1558354,"name":"Sarah M. Pugliese","orcid":"0009-0004-1745-3564","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Connectome simulations identify a central pattern generator circuit for fly walking","abstract":"<jats:title>Abstract</jats:title>\n                <jats:p>\n                  Animal locomotion relies on rhythmic body movements driven by central pattern generators (CPGs): neural circuits that produce oscillating output without oscillating input. However, the circuit structure of a CPG for walking is not known in any animal. To identify the cells and synapses that underlie rhythmic leg movement in walking flies, we developed dynamic simulations of the\n                  <jats:italic>Drosophila</jats:italic>\n                  ventral nerve cord (VNC) connectomes. A computational activation screen of descending neurons from the central brain identified DNg100—a known command neuron for walking—as the top driver of rhythmic leg motor activity. Simulated network pruning isolated a minimal rhythm-generating circuit consisting of one inhibitory and two excitatory interneurons; this three-neuron circuit was necessary and sufficient for motor rhythms across all six legs and in four connectome datasets. Simulations also predicted that a separate descending pathway (DNb08) drives rhythmic leg movements, which we confirmed experimentally using optogenetics in behaving flies. Our results reveal the cellular identity and synaptic structure of a putative CPG circuit for walking and other rhythmic leg movements in flies.\n                </jats:p>","is_dataset_classified":null,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"42094485","pmcid":null,"openalex_id":"https://openalex.org/W4414598781","authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2025,"count":1},{"year":2026,"count":6}],"oa_status":"green","license":"cc-by-nc-nd","oa_locations":[{"url":"https://doi.org/10.1101/2025.09.12.675944","host_type":"repository"},{"url":"https://doi.org/10.1101/2025.09.12.675944","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/2025.09.12.675944","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/42094485","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13142387/","host_type":"repository"}],"fields_of_study":["Neurobiology and Insect Physiology Research","Zebrafish Biomedical Research Applications","Neural dynamics and brain function"],"mesh_terms":[],"keywords":["Central pattern generator","Optogenetics","Connectome","Excitatory postsynaptic potential","Digital pattern generator","Rhythm","Inhibitory postsynaptic potential","Biological neural network","Neurophysiology"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-10T01:45:50.249862Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}