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Here, we leveraged unbiased single-nucleus transcriptional profiling and targeted in situ detection to identify\n            <jats:italic>Reln<\/jats:italic>\n            (encoding the secreted glycoprotein, Reelin) as a marker of cocaine-activated neuronal populations within the rat NAc. A CRISPR interference approach enabling selective\n            <jats:italic>Reln<\/jats:italic>\n            knockdown in the adult NAc altered expression of calcium signaling genes, promoted a transcriptional trajectory consistent with loss of cocaine sensitivity, and decreased MSN excitability. Behaviorally,\n            <jats:italic>Reln<\/jats:italic>\n            knockdown prevented cocaine locomotor sensitization, abolished cocaine place preference memory, and decreased cocaine self-administration behavior. These results identify Reelin as a critical mechanistic link between neuronal activation and cocaine-induced behavioral adaptations.\n          <\/jats:p>","DOI":"10.1126\/sciadv.ads4441","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T18:45:32Z","timestamp":1743014732000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":7,"title":["Reelin marks cocaine-activated striatal neurons, promotes neuronal excitability, and regulates cocaine reward"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9187-0412","authenticated-orcid":true,"given":"Kasey L.","family":"Brida","sequence":"first","affiliation":[{"name":"Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8706-292X","authenticated-orcid":true,"given":"Emily T.","family":"Jorgensen","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3560-4747","authenticated-orcid":true,"family":"Robert A. 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