{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:23:13Z","timestamp":1785421393474,"version":"3.56.0"},"posted":{"date-parts":[[2026,4,30]]},"group-title":"Neuroscience","reference-count":70,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["BRFSG-2020-08"],"award-info":[{"award-number":["BRFSG-2020-08"]}],"id":[{"id":"https:\/\/ror.org\/0492gsr48","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,30]]},"abstract":"<jats:title>\n                  A\n                  <jats:sc>bstract<\/jats:sc>\n                <\/jats:title>\n                <jats:p>\n                  Opioid withdrawal produces a protracted aversive state that is a driving factor towards relapse for patients with opioid use disorder. The habenula is known to mediate symptoms of withdrawal across several substance use disorders, including alcohol, nicotine, and opioid use disorder. However, it is unclear which habenular populations contribute to withdrawal symptoms. Here, we identify a cell type marker for habenular neurons active during opioid withdrawal. Using immediate early gene analysis, we find that glutamic acid decarboxylase 2-expressing (GAD2\n                  <jats:sup>+<\/jats:sup>\n                  ) cells in the lateral habenula (LHb\n                  <jats:sup>GAD2<\/jats:sup>\n                  ) increase activity in response to both spontaneous and naloxone-precipitated opioid withdrawal in mice. Recording neural activity\n                  <jats:italic>in vivo<\/jats:italic>\n                  revealed transient activity at the presentation of aversive stimuli, and a sustained increase in activity during aversive states such as opioid withdrawal and inescapable shock. These results highlight the cell type heterogeneity of the habenula, and the role of specific cell types in opioid withdrawal.\n                <\/jats:p>","DOI":"10.64898\/2026.04.29.721196","type":"posted-content","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T05:55:12Z","timestamp":1777614912000},"source":"Crossref","is-referenced-by-count":0,"title":["Opioid withdrawal engages a habenular subpopulation responsive to aversive states"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0185-808X","authenticated-orcid":false,"given":"Leah G","family":"Blankenship","sequence":"first","affiliation":[{"name":"Department of Biology, University of Oregon, Franklin Blvd, Eugene, OR 97403"},{"name":"Institute of Neuroscience, University of Oregon, Franklin Blvd, Eugene, OR 97403"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Moore","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, University of Oregon, Franklin Blvd, Eugene, OR 97403"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3315-595X","authenticated-orcid":false,"given":"Blake","family":"Holcomb","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, University of Oregon, Franklin Blvd, Eugene, OR 97403"},{"name":"St. Jude Children\u2019s Research Hospital, Danny Thomas Pl, Memphis, TN 38105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Salinas","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Oregon, Franklin Blvd, Eugene, OR 97403"},{"name":"Institute of Neuroscience, University of Oregon, Franklin Blvd, Eugene, OR 97403"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1172-6523","authenticated-orcid":false,"given":"Emily L","family":"Sylwestrak","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Oregon, Franklin Blvd, Eugene, OR 97403"},{"name":"Institute of Neuroscience, University of Oregon, Franklin Blvd, Eugene, OR 97403"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026050513300911000_2026.04.29.721196v1.1","unstructured":"Centers for Disease Control and Prevention, National Center for Health Statistics. 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