{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T09:30:54Z","timestamp":1787995854886,"version":"build-2784847793"},"reference-count":58,"publisher":"National Academy of Sciences","issue":"41","license":[{"start":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T00:00:00Z","timestamp":1696464000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19J22270"],"award-info":[{"award-number":["19J22270"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K20688 and 22K15225"],"award-info":[{"award-number":["21K20688 and 22K15225"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21H02526 20KK0177 and 18H02477"],"award-info":[{"award-number":["21H02526 20KK0177 and 18H02477"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["26293046 26640041 16H01271 17H05563 18H05124 18KK0223 and 18H02523"],"award-info":[{"award-number":["26293046 26640041 16H01271 17H05563 18H05124 18KK0223 and 18H02523"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,10,10]]},"abstract":"<jats:p>Narcolepsy is a sleep disorder caused by deficiency of orexin signaling. However, the neural mechanisms by which deficient orexin signaling causes the abnormal rapid eye movement (REM) sleep characteristics of narcolepsy, such as cataplexy and frequent transitions to REM states, are not fully understood. Here, we determined the activity dynamics of orexin neurons during sleep that suppress the abnormal REM sleep architecture of narcolepsy. Orexin neurons were highly active during wakefulness, showed intermittent synchronous activity during non-REM (NREM) sleep, were quiescent prior to the transition from NREM to REM sleep, and a small subpopulation of these cells was active during REM sleep. Orexin neurons that lacked orexin peptides were less active during REM sleep and were mostly silent during cataplexy. Optogenetic inhibition of orexin neurons established that the activity dynamics of these cells during NREM sleep regulate NREM\u2013REM sleep transitions. Inhibition of orexin neurons during REM sleep increased subsequent REM sleep in \u201corexin intact\u201d mice and subsequent cataplexy in mice lacking orexin peptides, indicating that the activity of a subpopulation of orexin neurons during the preceding REM sleep suppresses subsequent REM sleep and cataplexy. Thus, these results identify how deficient orexin signaling during sleep results in the abnormal REM sleep architecture characteristic of narcolepsy.<\/jats:p>","DOI":"10.1073\/pnas.2301951120","type":"journal-article","created":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T13:58:08Z","timestamp":1696514288000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":40,"title":["Deficiency of orexin signaling during sleep is involved in abnormal REM sleep architecture in narcolepsy"],"prefix":"10.1073","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2818-4935","authenticated-orcid":false,"given":"Hiroto","family":"Ito","sequence":"first","affiliation":[{"name":"Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan"},{"name":"Department of Neural Regulation, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"},{"name":"Japan Society for the Promotion of Science Research Fellowship for Young Scientists, Tokyo 102-0083, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0206-0256","authenticated-orcid":false,"given":"Noriaki","family":"Fukatsu","sequence":"additional","affiliation":[{"name":"Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan"},{"name":"Department of Neural Regulation, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6470-8357","authenticated-orcid":false,"given":"Sheikh Mizanur","family":"Rahaman","sequence":"additional","affiliation":[{"name":"Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan"},{"name":"Department of Neural Regulation, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0185-2040","authenticated-orcid":false,"given":"Yasutaka","family":"Mukai","sequence":"additional","affiliation":[{"name":"Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan"},{"name":"Department of Neural Regulation, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9552-6800","authenticated-orcid":false,"given":"Shuntaro","family":"Izawa","sequence":"additional","affiliation":[{"name":"Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan"},{"name":"Department of Neural Regulation, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Ono","sequence":"additional","affiliation":[{"name":"Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan"},{"name":"Department of Neural Regulation, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6823-0094","authenticated-orcid":false,"given":"Thomas S.","family":"Kilduff","sequence":"additional","affiliation":[{"name":"Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, CA 94025"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6099-7306","authenticated-orcid":false,"given":"Akihiro","family":"Yamanaka","sequence":"additional","affiliation":[{"name":"Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan"},{"name":"Department of Neural Regulation, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"},{"name":"Chinese Institute for Brain Research, Beijing 102206, China"},{"name":"National Institute for Physiological Sciences, Aichi 444-8585, Japan"},{"name":"National Institutes of Natural Sciences, Aichi 444-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2023,10,5]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/22.1.11"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-7634(00)00037-3"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17401-3"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsy046"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsaa003"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.118.3062.273"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02765-w"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyg.2020.01662"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abl6618"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13938"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2015.06.038"},{"key":"e_1_3_4_12_2","article-title":"Functional roles of REM sleep","author":"Mukai Y.","year":"2022","unstructured":"Y. Mukai, A. Yamanaka, Functional roles of REM sleep. Neurosci. Res., 10.1016\/j.neures.2022.12.009 (2022).","journal-title":"Neurosci. Res."},{"key":"e_1_3_4_13_2","doi-asserted-by":"crossref","unstructured":"L. de Lecea The hypocretins: Hypothalamus-specific peptides with neuroexcitatory activity. Proc. Natl. Acad. Sci. U.S.A. 95 322\u2013327 (1998).","DOI":"10.1073\/pnas.95.1.322"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80949-6"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/79690"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)00058-1"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81973-X"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81965-0"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0586-04.2004"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2630-12.2012"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1500587"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2017.02.010"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-019-0226-9"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-018-0097-x"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2017.01.021"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2001.85.5.2008"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-4-19"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2005.04104.x"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1887-05.2005"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.04.035"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2008.02.058"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.01061"},{"key":"e_1_3_4_33_2","doi-asserted-by":"crossref","unstructured":"S. B. Li Hyperexcitable arousal circuits drive sleep instability during aging. Science 375 eabh3021 (2022). eabh3021","DOI":"10.1126\/science.abh3021"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep29480"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10683-2"},{"key":"e_1_3_4_36_2","doi-asserted-by":"crossref","unstructured":"S. Chowdhury Dissociating orexin-dependent and -independent functions of orexin neurons using novel Orexin-Flp knock-in mice. Elife 8 e44927 (2019). e44927","DOI":"10.7554\/eLife.44927"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0400590101"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smrv.2021.101546"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-022-00907-w"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.5665\/sleep\/32.1.111"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00331-3"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0784-11.2011"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2013.05.021"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0311-19.2019"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt069"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2869.2011.00945.x"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2012.06.011"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aax9238"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(03)00299-7"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2120-10.2010"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.03.010"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.11.032"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)00293-8"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0073-14.2014"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.5665\/sleep.4908"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(99)01336-0"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(04)00247-8"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-021-01390-2"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2301951120","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T13:59:06Z","timestamp":1696514346000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2301951120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,5]]},"references-count":58,"journal-issue":{"issue":"41","published-print":{"date-parts":[[2023,10,10]]}},"alternative-id":["10.1073\/pnas.2301951120"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2301951120","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,5]]},"assertion":[{"value":"2023-02-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2301951120"}}