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Adv."],"published-print":{"date-parts":[[2026,9,11]]},"abstract":"<jats:p>\n                    Sleep homeostasis maintains the sleep-wake balance through sleep pressure, a process partly orchestrated by the accumulation of extracellular adenosine (eADO). Microglial Ca\n                    <jats:sup>2+<\/jats:sup>\n                    activity has been implicated in sleep regulation, but the mechanism whereby microglia sense sleep pressure remains unclear. Here, we show that microglia regulate sleep homeostasis through brain state\u2013dependent calcium ion activity driven by adenosine A\n                    <jats:sub>3<\/jats:sub>\n                    receptor (A\n                    <jats:sub>3<\/jats:sub>\n                    R) signaling. Using miniaturized two-photon microscopy in freely behaving mice, we demonstrate that microglial calcium ion activity is rapidly altered by brain-state transitions. Pharmacological experiments reveal that microglial calcium ion dynamics are predominantly mediated by A\n                    <jats:sub>3<\/jats:sub>\n                    R in response to brain state\u2013dependent eADO oscillations. Microglia-specific deletion of A\n                    <jats:sub>3<\/jats:sub>\n                    R attenuates these state-dependent calcium ion dynamics, impairs microglial morphological plasticity across sleep-wake cycles, and leads to sleep fragmentation by increasing transitions between wakefulness and non-rapid eye movement (NREM) sleep. Together, these findings establish that microglia contribute to sleep homeostasis by stabilizing both wakefulness and NREM sleep, a process partly involving eADO-A\n                    <jats:sub>3<\/jats:sub>\n                    R signaling.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aef3957","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T17:58:29Z","timestamp":1789149509000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Microglia stabilize sleep homeostasis via adenosine A\n                    <sub>3<\/sub>\n                    receptor signaling"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3775-3818","authenticated-orcid":true,"given":"Zhong","family":"Zhao","sequence":"first","affiliation":[{"name":"PKU-Nanjing Institute of Translational Medicine, Nanjing 210032, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7289-8054","authenticated-orcid":true,"given":"Xiaochun","family":"Gu","sequence":"additional","affiliation":[{"name":"PKU-Nanjing Institute of Translational Medicine, Nanjing 210032, China."},{"name":"National Platform for Medical Engineering Education Integration, Southeast University, Nanjing 211899, China."},{"name":"Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging &amp; Interventional Radiology, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing 210009, China."},{"name":"Key Laboratory of Developmental Genes and Human Diseases, Department of Histology Embryology, Medical School, Southeast University, Nanjing 210009, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3282-9555","authenticated-orcid":true,"given":"Jing","family":"Yu","sequence":"additional","affiliation":[{"name":"PKU-Nanjing Institute of Translational Medicine, Nanjing 210032, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueli","family":"Chen","sequence":"additional","affiliation":[{"name":"PKU-Nanjing Institute of Translational Medicine, Nanjing 210032, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"PKU-Nanjing Institute of Translational Medicine, Nanjing 210032, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhao","sequence":"additional","affiliation":[{"name":"PKU-Nanjing Institute of Translational Medicine, Nanjing 210032, China."},{"name":"Nanjing Raygenitm Biotech Co. Ltd., Nanjing 210032, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Ye","sequence":"additional","affiliation":[{"name":"PKU-Nanjing Institute of Translational Medicine, Nanjing 210032, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9604-6702","authenticated-orcid":true,"given":"Heping","family":"Cheng","sequence":"additional","affiliation":[{"name":"PKU-Nanjing Institute of Translational Medicine, Nanjing 210032, China."},{"name":"Nanjing Raygenitm Biotech Co. Ltd., Nanjing 210032, China."},{"name":"National Biomedical Imaging Center, Beijing 100871, China."},{"name":"State Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","first-page":"195","article-title":"A two process model of sleep regulation","volume":"1","author":"Borb\u00e9ly A. A.","year":"1982","unstructured":"A. A. Borb\u00e9ly, A two process model of sleep regulation. Hum. Neurobiol. 1, 195\u2013204 (1982).","journal-title":"Hum. Neurobiol."},{"key":"e_1_3_2_3_2","first-page":"557","article-title":"Sleep homeostasis and models of sleep regulation","volume":"14","author":"Borb\u00e9ly A. A.","year":"1999","unstructured":"A. A. Borb\u00e9ly, P. 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