{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:09:50Z","timestamp":1792786190883,"version":"4.5.0"},"posted":{"date-parts":[[2025,4,3]]},"group-title":"Neuroscience","reference-count":131,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T00:00:00Z","timestamp":1743638400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"National Institute of General Medical Sciences","award":["R35GM146751"],"award-info":[{"award-number":["R35GM146751"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,15]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                <jats:p>Neural circuits underlying unconsciousness remain poorly defined. We test the hypothesis that unconsciousness arises from specific, distributed circuits using general anesthesia in mice as a reproducible model. We identify a cortical-to-subcortical shift in neural activity during isoflurane anesthesia that is organized into nine discrete functional communities mapped at single-cell resolution. The lateral parabrachial nucleus (LPB) emerges as a central hub, exhibiting high interconnectivity, spontaneous firing under anesthesia, and preferential recruitment during reactivation of the brain-wide ensemble confirmed by single unit recordings. Chemogenetic reactivation of the captured brain-wide ensemble induces sedation, slow wave oscillations, hypothermia, and analgesia, which are components of anesthesia-induced unconsciousness. Reactivation of the LPB ensemble alone recapitulates a subset of these effects. Together, we define a global neural substrate for unconsciousness and recapitulate its dissociable autonomic, neurophysiologic, and behavioral effects using brain-wide ensemble manipulations. These results establish a neural circuit framework for anesthesia-induced unconsciousness in the mammalian brain.<\/jats:p>\n                <jats:sec>\n                  <jats:title>HIGHLIGHTS<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>A distributed brain-wide ensemble comprises anesthesia unconsciousness<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Lateral parabrachial nucleus is a key, preferentially activated hub<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Brain-wide or parabrachial ensemble re-activation induces altered consciousness -<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.1101\/2025.03.28.646066","type":"posted-content","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T05:13:14Z","timestamp":1744089194000},"source":"Crossref","is-referenced-by-count":2,"title":["Anesthesia unconsciousness recruits dynamic parabrachial activity within a distributed brain-wide ensemble"],"prefix":"10.64898","author":[{"given":"Kevin N.","family":"Schneider","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA"},{"name":"Department of Neurobiology and Biophysics, University of Washington, Seattle, WA"},{"name":"Center for Excellence in the Neurobiology of Addiction, Pain and Emotion, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minke H.C.","family":"Nota","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, 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