{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:07:50Z","timestamp":1774483670531,"version":"3.50.1"},"posted":{"date-parts":[[2024,5,20]]},"group-title":"Neuroscience","reference-count":33,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T00:00:00Z","timestamp":1716163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,1,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>We recently reported that the risk of cocaine relapse is linked to hyperexcitability in the secondary motor cortex (M2) after prolonged withdrawal following intravenous self-administration (IVSA). However, the neuronal mechanisms underlying drug-taking behaviors and the response of M2 neurons to contingent drug delivery remain poorly understood.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    Mice received cocaine as reinforcement (RNF) following active lever presses (ALP) but not inactive lever presses (ILP). Using\n                    <jats:italic>in vivo<\/jats:italic>\n                    calcium imaging during cocaine IVSA, we tracked M2 neuronal activity with single-cell resolution. We then analyzed Ca\n                    <jats:sup>2+<\/jats:sup>\n                    transients in M2 at the early\n                    <jats:italic>vs<\/jats:italic>\n                    . late stages during the 1-hr daily sessions on IVSA Day 1 and Day 5.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    M2 neurons adapted to both operant behaviors and drug exposure history. Specifically, saline mice showed a reduction in both saline taking behaviors and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    transient frequency with the 1-hr session. In contrast, cocaine mice maintained high ALP and RNF counts, with increased Ca\n                    <jats:sup>2+<\/jats:sup>\n                    transient frequency and amplitude on Day 1, persisting through Day 5. Compared to saline controls, cocaine mice exhibited a lower % of positively responsive neurons (Pos) and higher % of negatively responsive neurons (Neg) before ALP and after RNF, a difference not seen before ILP. Furthermore, as drug-taking behaviors progressed during the daily session, cocaine mice showed greater neuronal engagement with a larger population, particularly linked to ALP and RNF, with reduced overlap in neurons associated with ILP.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The M2 undergoes dynamic neuronal adaptations during early drug-taking behaviors, indicating its role as a potential substrate mediating the persistence of drug-seeking behaviors in cocaine relapse.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.05.20.594996","type":"posted-content","created":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T23:50:11Z","timestamp":1716249011000},"source":"Crossref","is-referenced-by-count":3,"title":["Decoding Secondary Motor Cortex Neuronal Activity during Cocaine Self-Administration: Insights from Longitudinal\n                  <i>in vivo<\/i>\n                  Calcium Imaging"],"prefix":"10.64898","author":[{"given":"Yingying","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haoying","family":"Fu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amith","family":"Korada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michal A.","family":"Lange","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chandrashekar","family":"Rayanki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongbing","family":"Lai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiaofen","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changyong","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yao-Ying","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025010706300653000_2024.05.20.594996v2.1","doi-asserted-by":"publisher","DOI":"10.1038\/nature17955"},{"key":"2025010706300653000_2024.05.20.594996v2.2","doi-asserted-by":"publisher","DOI":"10.1007\/s40261-014-0192-3"},{"key":"2025010706300653000_2024.05.20.594996v2.3","doi-asserted-by":"crossref","unstructured":"Dong, Z. , Mau, W. , Feng, Y. , Pennington, Z. , Chen, L. , Zaki, Y. , Rajan, K. , Shuman, T. , Aharoni, D. , Cai, D.J. , 2021. 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