{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T01:39:45Z","timestamp":1780105185662,"version":"3.54.0"},"reference-count":40,"publisher":"Wiley","issue":"39","license":[{"start":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS094571"],"award-info":[{"award-number":["R01NS094571"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The daily cycles of sleep and arousal are among the most prominent biological rhythms under circadian control. While the role of the suprachiasmatic nucleus (SCN) as the master circadian pacemaker is well\u2010established, the molecular and circuit mechanisms by which it regulates the rhythms of sleep and arousal remain poorly understood. It has previously shown that the\n                    <jats:italic>Drosophila<\/jats:italic>\n                    clock\u2010output molecule Wide Awake (WAKE) and its mammalian homolog mWAKE are expressed in fly clock neurons and dorsomedial hypothalamus neurons that promote arousal. Here, it is investigated whether mWAKE labels an arousal\u2010promoting SCN subcircuit in mice. Broad chemogenetic activation and inhibition of mWAKE\n                    <jats:sup>+<\/jats:sup>\n                    cells lead to a marked increase in wakefulness and a stupor\u2010like phenotype, respectively. Optogenetic activation specifically of mWAKE\u2010expressing neurons in the SCN (SCN\n                    <jats:sup>mWAKE<\/jats:sup>\n                    neurons) promotes arousal, while genetic knockout of mWAKE or impairment of CLOCK function in these neurons enhances wakefulness selectively at night. The latter phenotype corresponds to a specific increase in nighttime spiking of SCN\n                    <jats:sup>mWAKE<\/jats:sup>\n                    neurons in\n                    <jats:italic>mWake<\/jats:italic>\n                    mutants. At the circuit level, SCN\n                    <jats:sup>mWAKE<\/jats:sup>\n                    neuron signaling to the subparaventricular zone (SPZ) yields a stronger arousal phenotype. Together, these findings suggest that the genetic mechanisms regulating circadian control of sleep and arousal are evolutionarily conserved and define a clock\u2010regulated neural network important for rhythmic arousal.\n                  <\/jats:p>","DOI":"10.1002\/advs.202505131","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T10:33:03Z","timestamp":1753093983000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Subcircuit in the Suprachiasmatic Nucleus Generates Wakefulness"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6979-066X","authenticated-orcid":false,"given":"Qiang","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore MD 21205 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Soo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore MD 21205 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiali","family":"Xiong","sequence":"additional","affiliation":[{"name":"Biochemistry Cellular and Molecular Biology Graduate Program Johns Hopkins University School of Medicine  Baltimore MD 21205 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahin","family":"Ahmadi","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore MD 21205 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin J.","family":"Bell","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore MD 21205 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet F.","family":"Keles","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore MD 21205 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1329-0655","authenticated-orcid":false,"given":"Mark N.","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore MD 21205 USA"},{"name":"Solomon H. Snyder Department of Neuroscience Johns Hopkins University School of Medicine  Baltimore MD 21205 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,21]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1177\/074873098128999952"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2215"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-073109-130051"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.16233"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0205-18.2018"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.08.001"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(01)02890-6"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1109-07.2007"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1322-18.2018"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0363-20.2021"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.02.005"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adn8350"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17197-2"},{"key":"e_1_2_9_14_1","author":"Wu Y.","year":"2025","journal-title":"BioRxiv"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.01.040"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.09.016"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-41877-4"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2024.08.013"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.25066"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005344"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3086"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1169657"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.68179"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00027.2019"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(06)53014-6"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsz023"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-13-04864.2001"},{"key":"e_1_2_9_28_1","first-page":"91","volume":"63","author":"Toth L. 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