{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:19:06Z","timestamp":1785406746147,"version":"3.56.0"},"posted":{"date-parts":[[2026,4,24]]},"group-title":"Neuroscience","reference-count":160,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["R00NS112417"],"award-info":[{"award-number":["R00NS112417"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"award":["BRFSG-2023-01"],"award-info":[{"award-number":["BRFSG-2023-01"]}],"id":[{"id":"https:\/\/ror.org\/0492gsr48","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"crossref","award":["GT1709"],"award-info":[{"award-number":["GT1709"]}],"id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","award":["T32AG071745"],"award-info":[{"award-number":["T32AG071745"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,24]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>\n                  Exercise broadly affects the basal ganglia, brain structures involved in motor coordination. Exercise-induced changes in these regions can improve pathological conditions such as Parkinson\u2019s disease and substance use disorders. Importantly, biological sex is a significant factor in the effects of exercise and in the presentation of these basal ganglia-related conditions. Here, we find surprising sex differences in exercise\u2019s influence over motor coordination and neural activity across three extended basal ganglia structures: dorsomedial striatum cholinergic interneurons (CINs), substantia nigra pars compacta (SNc) dopaminergic neurons, and caudal pedunculopontine nucleus (PPN) cholinergic neurons. Using voluntary wheel running, accelerating rotarod,\n                  <jats:italic>ex vivo<\/jats:italic>\n                  electrophysiology, and morphological reconstructions, we found that exercise enhances motor coordination, increases SNc excitability, and strengthens excitatory input onto the PPN selectively in female mice. By contrast, exercise increases spontaneous firing rate and reduces dendritic complexity selectively in male CINs. These data reveal sex-specific exercise effects correlated across behavioral and cellular levels.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Abstract Figure<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"720719v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>One week of exercise enhances motor coordination in females but not males<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Exercise increases SNc excitability and excitatory input onto the PPN in females<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Exercise increases dorsomedial striatal cholinergic neurons activity in males<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Baseline sex differences in morphology of striatal cholinergic and SNc neurons<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.64898\/2026.04.24.720719","type":"posted-content","created":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T12:15:15Z","timestamp":1777119315000},"source":"Crossref","is-referenced-by-count":0,"title":["Sex-specific effects of exercise on motor coordination and extended basal ganglia physiology"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6456-6156","authenticated-orcid":false,"given":"Valerie J.","family":"Lewitus","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA 20007"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5909-5102","authenticated-orcid":false,"given":"Lindsey A.","family":"Russ","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA 20007"},{"name":"Department of Pharmacology & Physiology, Georgetown University Medical Center, Washington, DC, USA 20007"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5585-4981","authenticated-orcid":false,"given":"Chelsea B.","family":"Scott","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA 20007"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia M.","family":"Kruszewski","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA 20007"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8808-8010","authenticated-orcid":false,"given":"Giorgi","family":"Shautidze","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA 20007"},{"name":"Department of Pharmacology & Physiology, Georgetown University Medical Center, Washington, DC, USA 20007"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0583-7374","authenticated-orcid":false,"given":"Zachary A.","family":"Colon","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA 20007"},{"name":"Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC, USA 20007"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8854-9659","authenticated-orcid":false,"given":"Shirley Q.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA 20007"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1969-0775","authenticated-orcid":false,"suffix":"Jr","given":"Joel A.","family":"Walker","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA 20007"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asia","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA 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