{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T22:06:32Z","timestamp":1789164392045,"version":"build-2803163510"},"posted":{"date-parts":[[2025,11,10]]},"group-title":"Neuroscience","reference-count":70,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/100000027","name":"NIAAA","doi-asserted-by":"crossref","award":["AA023288"],"award-info":[{"award-number":["AA023288"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000027","name":"NIAAA","doi-asserted-by":"crossref","award":["AA007474"],"award-info":[{"award-number":["AA007474"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000027","name":"NIAAA","doi-asserted-by":"crossref","award":["AA031433"],"award-info":[{"award-number":["AA031433"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Chronic alcohol misuse causes cognitive deficits and functional adaptations in the prefrontal cortex (PFC) that facilitate excessive drinking and increase relapse probability during prolonged withdrawal. Positive K\n                  <jats:sub>V<\/jats:sub>\n                  7 channel modulation reduces alcohol intake in high-drinking rodents, but the impact of alcohol dependence on cortical K\n                  <jats:sub>V<\/jats:sub>\n                  7 physiology and its role in cognitive impairments are understudied. Here, we demonstrate spatial working memory deficits and physiological adaptations in intrinsic excitability and K\n                  <jats:sub>V<\/jats:sub>\n                  7 channel function in intratelencephalic PFC projection neurons in alcohol-dependent mice. CRISPR-SaCas9 deletion of\n                  <jats:italic>Kcnq3<\/jats:italic>\n                  in PFC neurons that project to the dorsomedial striatum mimicked physiological adaptations and working memory deficits produced by alcohol dependence. Furthermore, PFC microinfusion of the K\n                  <jats:sub>V<\/jats:sub>\n                  7 positive modulator retigabine rescued alcohol-induced working memory dysfunction. These findings identify an aberrant cortical mechanism responsible for alcohol-associated cognitive dysfunction, providing insights into a pharmacological treatment approach that can target both high drinking and cognitive impairments associated with alcohol use disorder.\n                <\/jats:p>","DOI":"10.1101\/2025.11.07.687180","type":"posted-content","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T17:00:15Z","timestamp":1762794015000},"source":"Crossref","is-referenced-by-count":0,"title":["Rescuing cognitive deficits in alcohol-dependent mice by targeting physiological adaptations in prefrontal cortex K\n                  <sub>V<\/sub>\n                  7 channels"],"prefix":"10.64898","author":[{"given":"Kathy L.","family":"Lindquist","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Charleston Alcohol Research Center, Medical University of South Carolina, Charleston, SC 29425, United 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Neuroscience, Charleston Alcohol Research Center, Medical University of South Carolina, Charleston, SC 29425, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry S.","family":"Zweifel","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Psychiatry & Behavioral Sciences, University of Washington, Seattle, WA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3738-3693","authenticated-orcid":false,"given":"Jennifer A.","family":"Rinker","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Charleston Alcohol Research Center, Medical University of South Carolina, Charleston, SC 29425, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0780-5971","authenticated-orcid":false,"given":"Patrick J.","family":"Mulholland","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, 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