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Mice lacking OX2R signaling had poor maintenance of wakefulness indicative of sleepiness and fragmented sleep and lacked any electrophysiological response to orexin-A in the wake-promoting neurons of the tuberomammillary nucleus. These defects were completely recovered by crossing them with mice that express Cre in the female germline, thus globally deleting the transcription-disrupter cassette. Then, by using an adeno-associated viral vector coding for Cre recombinase, we found that focal restoration of OX2R in neurons of the tuberomammillary nucleus and adjacent parts of the posterior hypothalamus completely rescued the sleepiness of these mice, but their fragmented sleep was unimproved. These observations demonstrate that the tuberomammillary region plays an essential role in the wake-promoting effects of orexins, but orexins must stabilize sleep through other targets.<\/jats:p>","DOI":"10.1073\/pnas.1012456108","type":"journal-article","created":{"date-parts":[[2011,3,1]],"date-time":"2011-03-01T22:35:37Z","timestamp":1299018937000},"page":"4471-4476","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":122,"title":["Orexin receptor 2 expression in the posterior hypothalamus rescues sleepiness in narcoleptic mice"],"prefix":"10.1073","volume":"108","author":[{"given":"Takatoshi","family":"Mochizuki","sequence":"first","affiliation":[{"name":"Department of Neurology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elda","family":"Arrigoni","sequence":"additional","affiliation":[{"name":"Department of Neurology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob N.","family":"Marcus","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215;"},{"name":"Merck Research Laboratories, West Point, PA 19486;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika L.","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Neurology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihoko","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Neurology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Honer","sequence":"additional","affiliation":[{"name":"F. 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