{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:18:29Z","timestamp":1792790309365,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,22]]},"group-title":"Neuroscience","reference-count":14,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["R01DA052317"],"award-info":[{"award-number":["R01DA052317"]}],"id":[{"id":"https:\/\/ror.org\/00fq5cm18","id-type":"ROR","asserted-by":"publisher"}]},{"award":["K99DA060930"],"award-info":[{"award-number":["K99DA060930"]}],"id":[{"id":"https:\/\/ror.org\/00fq5cm18","id-type":"ROR","asserted-by":"publisher"}]},{"award":["F32DA060662"],"award-info":[{"award-number":["F32DA060662"]}],"id":[{"id":"https:\/\/ror.org\/00fq5cm18","id-type":"ROR","asserted-by":"publisher"}]},{"award":["F32DA061606"],"award-info":[{"award-number":["F32DA061606"]}],"id":[{"id":"https:\/\/ror.org\/00fq5cm18","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Institute on Alcohol Abuse and Alcoholism","award":["R01AA030931"],"award-info":[{"award-number":["R01AA030931"]}],"id":[{"id":"https:\/\/ror.org\/02jzrsm59","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute on Alcohol Abuse and Alcoholism","award":["P60AA031124"],"award-info":[{"award-number":["P60AA031124"]}],"id":[{"id":"https:\/\/ror.org\/02jzrsm59","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute on Alcohol Abuse and Alcoholism","award":["F32AA032415"],"award-info":[{"award-number":["F32AA032415"]}],"id":[{"id":"https:\/\/ror.org\/02jzrsm59","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Drugs of abuse produce lasting adaptations in the striatum. A prominent theory holds that the early reinforcing effects of cocaine preferentially engage the ventral striatum, and repeated cocaine use recruits dorsal striatal systems associated with habitual drug-related behavior. However, this transition has largely been conceptualized on the population level, obscuring how it is implemented within individual neurons and how repeated drug exposure reorganizes drug responsivity within these circuits. Here, we used single-cell calcium imaging to examine ventral and dorsal striatal responses to acute and repeated cocaine exposure in mice. Cocaine broadly suppressed neuronal activity throughout the ventral and dorsal striatum. However, repeated exposure produced opposing changes in cocaine-modulated neurons across the ventral\u2013dorsal axis. The cocaine-activated population was reduced ventrally while expanding dorsally. Unique to dorsal striatum, repeated cocaine engendered two distinct features of activity: 1) Cocaine-activated cells had weak baseline coupling with the surrounding neuronal population and 2) The emergence of a subpopulation of neurons exhibiting regular, slow rhythmic activity in response to cocaine. Thus, repeated cocaine effects reflect a change in how the circuit is organized rather than simply how strongly it is engaged. This organization may allow cocaine to engage patterns of dorsal striatal activity that are largely absent under baseline conditions, creating a circuit state that becomes increasingly specific to the presence of the drug.<\/jats:p>","DOI":"10.64898\/2026.09.15.751852","type":"posted-content","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T20:00:16Z","timestamp":1790107216000},"source":"Crossref","is-referenced-by-count":0,"title":["Repeated cocaine reorganizes striatal ensembles along the ventral\u2013dorsal axis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8623-4542","authenticated-orcid":false,"given":"Michael Z.","family":"Leonard","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Vanderbilt University, Nashville, TN, USA"},{"name":"Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6106-4011","authenticated-orcid":false,"given":"Hannah B.","family":"Reiley","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Vanderbilt University, Nashville, TN, USA"},{"name":"Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ainoa Konomi","family":"Pilkati","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5366-1230","authenticated-orcid":false,"given":"Kathryn J.","family":"Bjornson","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Vanderbilt University, Nashville, TN, USA"},{"name":"Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxime","family":"Chev\u00e9e","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Vanderbilt University, Nashville, TN, USA"},{"name":"Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4723-0623","authenticated-orcid":false,"given":"Erin S.","family":"Calipari","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Vanderbilt University, Nashville, TN, USA"},{"name":"Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN, USA"},{"name":"Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA"},{"name":"Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA"},{"name":"Department of Psychiatry and Behavioral Sciences, Vanderbilt University, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026092506151699000_2026.09.15.751852v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2261"},{"key":"2026092506151699000_2026.09.15.751852v1.2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-14-06247.2002"},{"key":"2026092506151699000_2026.09.15.751852v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.12.019"},{"key":"2026092506151699000_2026.09.15.751852v1.4","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-psych-122414-033457"},{"key":"2026092506151699000_2026.09.15.751852v1.5","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5578-03.2004"},{"key":"2026092506151699000_2026.09.15.751852v1.6","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4305-05.2006"},{"key":"2026092506151699000_2026.09.15.751852v1.7","doi-asserted-by":"crossref","unstructured":"Takahashi, Y. , Roesch, M. R. , Stalnaker, T. A. & Schoenbaum, G. Cocaine exposure shifts the balance of associative encoding from ventral to dorsolateral striatum. Front Integr Neurosci 1, ihpa51247 (2007).","DOI":"10.3389\/neuro.07.011.2007"},{"key":"2026092506151699000_2026.09.15.751852v1.8","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1039-08.2008"},{"key":"2026092506151699000_2026.09.15.751852v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2005.03.030"},{"key":"2026092506151699000_2026.09.15.751852v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(98)00116-X"},{"key":"2026092506151699000_2026.09.15.751852v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2024.06.008"},{"key":"2026092506151699000_2026.09.15.751852v1.12","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.66048"},{"key":"2026092506151699000_2026.09.15.751852v1.13","doi-asserted-by":"crossref","first-page":"6084","DOI":"10.1038\/s41467-025-61004-9","article-title":"Cocaine-context memories are transcriptionally encoded in nucleus accumbens Arc ensembles","volume":"16","year":"2025","journal-title":"Nat Commun"},{"key":"2026092506151699000_2026.09.15.751852v1.14","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.1152\/jn.1999.81.5.2046","article-title":"Multisecond Oscillations in Firing Rate in the Basal Ganglia: Robust Modulation by Dopamine Receptor Activation and Anesthesia","volume":"81","year":"1999","journal-title":"Journal of Neurophysiology"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.09.15.751852","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T13:15:24Z","timestamp":1790342124000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.09.15.751852"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,22]]},"references-count":14,"URL":"https:\/\/doi.org\/10.64898\/2026.09.15.751852","relation":{},"subject":[],"published":{"date-parts":[[2026,9,22]]},"subtype":"preprint"}}