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Adv."],"published-print":{"date-parts":[[2026,10,23]]},"abstract":"<jats:p>\n                    Sleep disruption in obstructive sleep apnea syndrome is characterized by frequent microarousals and reduced sleep depth, yet the underlying mechanisms remain unclear. Here, we show that intermittent hypercapnic air (HA) induces time-locked microarousals, fragments sleep, reduces non\u2013rapid eye movement (NREM) sleep depth, and diminishes rapid eye movement (REM) sleep. HA exposure activates glutamatergic neurons in the nucleus tract solitary (NTS\n                    <jats:sup>Vglut2<\/jats:sup>\n                    ), and their optogenetic or chemogenetic activation is sufficient to trigger arousal and impair sleep. Projection-specific activation reveals that NTS\n                    <jats:sup>Vglut2<\/jats:sup>\n                    projections to the paraventricular nucleus (PVN), parabrachial nucleus (PB), paraventricular thalamus, and locus coeruleus (LC) promote arousal, whereas projections to the PB and LC additionally reduce NREM sleep depth. Inhibition of NTS\n                    <jats:sup>Vglut2<\/jats:sup>\n                    projection to the PVN significantly postpones HA-induced arousal. NTS\n                    <jats:sup>Vglut2<\/jats:sup>\n                    terminals monosynaptically activate corticotropin-releasing hormone neurons in the PVN (PVN\n                    <jats:sup>CRH<\/jats:sup>\n                    ), and inhibition of PVN\n                    <jats:sup>CRH<\/jats:sup>\n                    neurons or knockdown of\n                    <jats:italic toggle=\"yes\">Slc17a6<\/jats:italic>\n                    (encoding Vglut2), but not\n                    <jats:italic toggle=\"yes\">Crh<\/jats:italic>\n                    , delays hypercapnia-induced arousal. These findings identify neural circuits underlying hypercapnia-induced microarousal and reduced sleep depth.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aei1892","type":"journal-article","created":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T17:58:42Z","timestamp":1792778322000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Neural circuitry mediating hypercapnia-induced microarousal and impaired sleep depth"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0875-2244","authenticated-orcid":true,"given":"Chen","family":"Yang","sequence":"first","affiliation":[{"name":"Department of General Practice, Department of Geriatric Medicine, Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai Institute of Geriatrics and Gerontology, Huadong Hospital, Institute for Translational Brain Research, Center for Clinical Neuro-AI, State Key Laboratory of Brain Function and Disorders and MOE Frontiers Center for Brain Science, MOE Innovative Center for New Drug Development of Immune Inflammatory Diseases, Joint International Research Laboratory of Sleep, Fudan University, Shanghai 200040, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8904-2693","authenticated-orcid":true,"given":"Wen-Xuan","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of General Practice, Department of Geriatric Medicine, Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai Institute of Geriatrics and Gerontology, Huadong Hospital, Institute for Translational Brain Research, Center for Clinical Neuro-AI, State Key Laboratory of Brain Function and Disorders and MOE Frontiers Center for Brain Science, MOE Innovative Center for New Drug Development of Immune Inflammatory Diseases, Joint International Research Laboratory of Sleep, Fudan University, Shanghai 200040, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0767-2316","authenticated-orcid":true,"given":"Wen-Xu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of General Practice, Department of Geriatric Medicine, Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai Institute of Geriatrics and Gerontology, Huadong Hospital, Institute for Translational Brain Research, Center for Clinical Neuro-AI, State Key Laboratory of Brain Function and Disorders and MOE Frontiers Center for Brain Science, MOE Innovative Center for New Drug Development of Immune Inflammatory Diseases, Joint International Research Laboratory of Sleep, Fudan University, Shanghai 200040, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Long","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of General Practice, Department of Geriatric Medicine, Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai Institute of Geriatrics and Gerontology, Huadong Hospital, Institute for Translational Brain Research, Center for Clinical Neuro-AI, State Key Laboratory of Brain Function and Disorders and MOE Frontiers Center for Brain Science, MOE Innovative Center for New Drug Development of Immune Inflammatory Diseases, Joint International Research Laboratory of Sleep, Fudan University, Shanghai 200040, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-Yi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of General Practice, Department of Geriatric Medicine, Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai Institute of Geriatrics and Gerontology, Huadong Hospital, Institute for Translational Brain Research, Center for Clinical Neuro-AI, State Key Laboratory of Brain Function and Disorders and MOE Frontiers Center for Brain Science, MOE Innovative Center for New Drug Development of Immune Inflammatory Diseases, Joint International Research Laboratory of Sleep, Fudan University, Shanghai 200040, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan-Ni","family":"He","sequence":"additional","affiliation":[{"name":"Department of General Practice, Department of Geriatric Medicine, Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai Institute of Geriatrics and Gerontology, Huadong Hospital, Institute for Translational Brain Research, Center for Clinical Neuro-AI, State Key Laboratory of Brain Function and Disorders and MOE Frontiers Center for Brain Science, MOE Innovative Center for New Drug Development of Immune Inflammatory Diseases, Joint International Research Laboratory of Sleep, Fudan University, Shanghai 200040, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of General Practice, Department of Geriatric Medicine, Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai Institute of Geriatrics and Gerontology, Huadong Hospital, Institute for Translational Brain Research, Center for Clinical Neuro-AI, State Key Laboratory of Brain Function and Disorders and MOE Frontiers Center for Brain Science, MOE Innovative Center for New Drug Development of Immune Inflammatory Diseases, Joint International Research Laboratory of Sleep, Fudan University, Shanghai 200040, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-hui","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of General Practice, Department of Geriatric Medicine, Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai Institute of Geriatrics and Gerontology, Huadong Hospital, Institute for Translational Brain Research, Center for Clinical Neuro-AI, State Key Laboratory of Brain Function and Disorders and MOE Frontiers Center for Brain Science, MOE Innovative Center for New Drug Development of Immune 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