{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T17:05:18Z","timestamp":1793207118904,"version":"4.5.0"},"reference-count":45,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"834","funder":[{"DOI":"10.13039\/100009068","name":"Universit\u00e4t Bern","doi-asserted-by":"publisher","award":["41-050"],"award-info":[{"award-number":["41-050"]}],"id":[{"id":"10.13039\/100009068","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","award":["725850"],"award-info":[{"award-number":["725850"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000854","name":"Human Frontier Science Program","doi-asserted-by":"publisher","award":["RGY0076\/2012"],"award-info":[{"award-number":["RGY0076\/2012"]}],"id":[{"id":"10.13039\/501100000854","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-21-CE16-0030-01"],"award-info":[{"award-number":["ANR-21-CE16-0030-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["CRSK-3_221163"],"award-info":[{"award-number":["CRSK-3_221163"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["32003B_215721"],"award-info":[{"award-number":["32003B_215721"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["310030E_205524\/1"],"award-info":[{"award-number":["310030E_205524\/1"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["31003A_156156"],"award-info":[{"award-number":["31003A_156156"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013348","name":"Innosuisse - Schweizerische Agentur f\u00fcr Innovationsf\u00f6rderung","doi-asserted-by":"publisher","award":["30664.1 IP-LS"],"award-info":[{"award-number":["30664.1 IP-LS"]}],"id":[{"id":"10.13039\/501100013348","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Bern","award":["41-040"],"award-info":[{"award-number":["41-040"]}]},{"name":"European Sleep Research Society","award":["Mobility Grant"],"award-info":[{"award-number":["Mobility Grant"]}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2026,1,28]]},"abstract":"<jats:p>Narcolepsy is caused by hypothalamic hypocretin\/orexin loss and characterized by cataplexy, a unique brain state triggered by emotion. Cataplexy shares features with rapid eye movement (REM) sleep, including muscle atonia and wake-like electroencephalographic activity. REM sleep is characterized by thermoregulatory suspension and, when the need for thermoregulatory responses is reduced as during ambient thermoneutral warming, melanin-concentrating hormone (MCH) neurons play a critical role in favoring REM sleep expression. However, it remains unknown whether REM sleep and cataplexy share thermomodulatory mechanisms. Here, we demonstrate that reduced skin temperatures and a widening of the distal-to-proximal skin temperature gradient precede cataplexy in both patients with narcolepsy and hypocretin-knockout (Hcrt-KO) narcoleptic mice. To test a causal role for skin temperature in cataplexy modulation, thermoneutral manipulation of skin temperature in Hcrt-KO mice revealed that skin cooling promoted cataplexy, whereas skin warming increased REM sleep. Fiber photometry showed that, at constant ambient temperatures (23\u00b0C), cataplexy and REM sleep were associated with increased MCH neuron activity. Skin cooling, however, reduced the MCH calcium imaging dynamics associated with cataplexy. Moreover, MCH optogenetic or chemogenetic manipulation recapitulated these effects, with MCH silencing favoring cataplexy and MCH activation driving REM sleep. Last, using the skin warming condition, we combined cFos staining and retrograde labeling and identified activated monosynaptic inputs from known thermoregulatory hubs such as the median preoptic nucleus, dorsomedial hypothalamus, and the parabrachial nucleus to MCH neurons. These findings unveil an unexplored role for skin thermal dynamics and hypothalamic MCH thermosensitivity in dissociating cataplexy and REM sleep.<\/jats:p>","DOI":"10.1126\/scitranslmed.adu8570","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T18:58:25Z","timestamp":1769626705000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Skin thermal dynamics and hypothalamic thermosensitivity dissociate REM sleep and cataplexy in narcolepsy"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1180-668X","authenticated-orcid":true,"given":"Bianca","family":"Viberti","sequence":"first","affiliation":[{"name":"Center for Experimental Neurology, Department of Neurology, Bern University Hospital (Inselspital) and University Bern, 3010 Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Bellini","sequence":"additional","affiliation":[{"name":"Center for Experimental Neurology, Department of Neurology, Bern University Hospital (Inselspital) and University Bern, 3010 Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5979-1535","authenticated-orcid":true,"given":"Amarine","family":"Chancel","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Claude Bernard Lyon 1, CNRS, INSERM, Lyon Neuroscience Research Center CRNL UMR 5292 U1028, SLEEP, F-69500 Bron, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7164-6584","authenticated-orcid":true,"given":"Francesca","family":"Col\u00f3","sequence":"additional","affiliation":[{"name":"Center for Experimental Neurology, Department of Neurology, Bern University Hospital (Inselspital) and University Bern, 3010 Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Branca","sequence":"additional","affiliation":[{"name":"Dipartimento dell\u2019educazione, della cultura e dello sport (DECS), Piazza Governo 7, 6501 Bellinzona, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5171-9581","authenticated-orcid":true,"given":"Anja","family":"Probst","sequence":"additional","affiliation":[{"name":"Center for Experimental Neurology, Department of Neurology, Bern University Hospital (Inselspital) and University Bern, 3010 Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0595-5621","authenticated-orcid":true,"given":"Julien","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Institute of Neuroinformatics, University of Zurich and ETH Zurich, 8057 Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Rusterholz","sequence":"additional","affiliation":[{"name":"Center for Experimental Neurology, Department of Neurology, Bern University Hospital (Inselspital) and University Bern, 3010 Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1211-8631","authenticated-orcid":true,"given":"Patrice","family":"Fort","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Claude Bernard Lyon 1, CNRS, INSERM, Lyon Neuroscience Research Center CRNL UMR 5292 U1028, SLEEP, F-69500 Bron, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0503-423X","authenticated-orcid":true,"given":"Pierre-Herv\u00e9","family":"Luppi","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Claude Bernard Lyon 1, CNRS, INSERM, Lyon Neuroscience Research Center CRNL UMR 5292 U1028, SLEEP, F-69500 Bron, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4535-0245","authenticated-orcid":true,"given":"Claudio L. A.","family":"Bassetti","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Bern, Murtenstrasse 11, 3008 Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2531-5175","authenticated-orcid":true,"given":"Antoine","family":"Adamantidis","sequence":"additional","affiliation":[{"name":"Center for Experimental Neurology, Department of Neurology, Bern University Hospital (Inselspital) and University Bern, 3010 Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3299-1318","authenticated-orcid":true,"given":"Markus H.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Center for Experimental Neurology, Department of Neurology, Bern University Hospital (Inselspital) and University Bern, 3010 Bern, Switzerland."},{"name":"Ohio Sleep Medicine Institute, 4975 Bradenton Ave., Dublin, OH 43017, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-019-0226-9"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2869.2010.00851.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0586-04.2004"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsx170"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt069"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-020518-114546"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3909-11.2011"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00624"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(94)90112-0"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/29.11.1444"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2008.143610"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00887.2005"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.2741\/1054"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2018.00790"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3522"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2019.05.009"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.54275"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2018.08.012"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0017-20.2020"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.5665\/sleep\/32.1.111"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11395"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2022.04.004"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0811400106"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1887-05.2005"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5269-14.2015"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/32.9.1127"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsy046"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.5665\/sleep.6220"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/6.2.137"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.00336"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2018.05.054"},{"key":"e_1_3_2_33_2","doi-asserted-by":"crossref","unstructured":"R. Szymusiak \u201cBody temperature and sleep\u201d in Handbook of Clinical Neurology (Elsevier 2018) pp. 341\u2013351.","DOI":"10.1016\/B978-0-444-63912-7.00020-5"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1616255114"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.08.028"},{"key":"e_1_3_2_36_2","first-page":"R1240","article-title":"Neuronal discharge of preoptic\/anterior hypothalamic thermosensitive neurons: Relation to NREM sleep","volume":"269","author":"Alam M. N.","year":"1995","unstructured":"M. N. Alam, D. McGinty, R. Szymusiak, Neuronal discharge of preoptic\/anterior hypothalamic thermosensitive neurons: Relation to NREM sleep. Am. J. Physiol. 269, R1240\u2013R1249 (1995).","journal-title":"Am. J. Physiol."},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/43366"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.02.005"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygcen.2011.03.028"},{"key":"e_1_3_2_40_2","first-page":"620","article-title":"Value of the multiple sleep latency test (MSLT) for the diagnosis of narcolepsy","volume":"20","author":"Aldrich M. S.","year":"1997","unstructured":"M. S. Aldrich, R. D. Chervin, B. A. Malow, Value of the multiple sleep latency test (MSLT) for the diagnosis of narcolepsy. Sleep 20, 620\u2013629 (1997).","journal-title":"Sleep"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.5664\/jcsm.2922"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.5664\/jcsm.6882"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2023.171002"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abn0853"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2017.122"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1046-2023(03)00080-X"}],"container-title":["Science Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.adu8570","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T18:58:33Z","timestamp":1769626713000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.adu8570"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,28]]},"references-count":45,"journal-issue":{"issue":"834","published-print":{"date-parts":[[2026,1,28]]}},"alternative-id":["10.1126\/scitranslmed.adu8570"],"URL":"https:\/\/doi.org\/10.1126\/scitranslmed.adu8570","relation":{},"ISSN":["1946-6234","1946-6242"],"issn-type":[{"value":"1946-6234","type":"print"},{"value":"1946-6242","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,28]]},"assertion":[{"value":"2024-11-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-15","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadu8570"}}