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While the sublaterodorsal tegmental nucleus (SLD) is recognized for its role in REM sleep generation, the functional contribution of its GABAergic neurons (SLD\n                    <jats:sup>GABA<\/jats:sup>\n                    ) to sleep-wake regulation remains poorly understood. Here, we found that SLD\n                    <jats:sup>GABA<\/jats:sup>\n                    neurons function as a suppressor of wakefulness in both healthy (i.e.,\n                    <jats:italic>orexin<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>+\/+<\/jats:italic>\n                    <\/jats:sup>\n                    ) and narcoleptic (i.e.,\n                    <jats:italic>orexin<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    ) mice. In healthy mice, optogenetic silencing of SLD\n                    <jats:sup>GABA<\/jats:sup>\n                    neurons rapidly induced robust wakefulness, while enhancing cortical and motor activity. Conversely, optogenetic activation of these neurons suppressed wakefulness and promoted NREM sleep. We found traces of SLD\n                    <jats:sup>GABA<\/jats:sup>\n                    axonal projections to wake-promoting brain regions, providing an anatomical basis for their wake-suppressing effects. Importantly, we discovered that SLD\n                    <jats:sup>GABA<\/jats:sup>\n                    neurons play a pathological role in narcolepsy: their activation in orexin-deficient narcoleptic mice triggered characteristic sleep attacks\u2014rapid intrusions of NREM sleep during active wakefulness\u2014while silencing these neurons rescued animals from both sleep attacks and cataplexy. Collectively, these findings establish SLD\n                    <jats:sup>GABA<\/jats:sup>\n                    neurons as a key regulator of arousal state transitions and identify them as a novel therapeutic target for the treatment of narcolepsy.\n                  <\/jats:p>","DOI":"10.1371\/journal.pbio.3003303","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T17:28:46Z","timestamp":1783531726000},"page":"e3003303","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["GABA neurons in the sublaterodorsal tegmental nucleus suppress wakefulness in healthy and narcoleptic mice"],"prefix":"10.1371","volume":"24","author":[{"given":"HanHee","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9008-0752","authenticated-orcid":true,"given":"Jimmy 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