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Here, we investigated a duration\u2010dependent astrocytic mechanism underlying cerebral blood volume (CBV) modulation by comparing neurovascular responses to brief (5 s) and prolonged (20 s) sensory stimulation, using in vivo intrinsic optical signal (IOS) imaging and two\u2010photon microscopy combined with electrophysiology and vascular cannulation. We show that prolonged stimulation selectively recruits an integrated astrocytic signaling cascade involving aquaporin\u20104 (AQP4)\u2010mediated volume changes, Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx through mechanosensitive transient receptor potential ankyrin 1 (TRPA1), and D\u2010serine release through the Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010dependent Bestrophin\u20101 (BEST1) channel. This signaling cascade drives sustained neuronal activity, leading to CBV modulation and sensory perception. Genetic ablation of each component in this pathway selectively impairs CBV responses, neuronal activity, and sensory behavior during prolonged stimulation, while exogenous D\u2010serine fully restores these deficits. We further demonstrate that tonic astrocytic D\u2010serine release via BEST1 directly regulates the basal tone of penetrating arterioles. These findings together identify astrocytic D\u2010serine as one of the key gliotransmitters that modulate CBV and neuronal activity during prolonged sensory demand and fine\u2010tune vascular tone in resting states.\n                  <\/jats:p>","DOI":"10.1002\/advs.77878","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:56:26Z","timestamp":1790744186000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Astrocytes Coordinate Neurovascular Coupling During Prolonged Sensory Demand via AQP4\/TRPA1\/BEST1\/D\u2010Serine Signaling"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3911-4104","authenticated-orcid":false,"given":"Kayoung","family":"Han","sequence":"first","affiliation":[{"name":"Center for Neuroscience Imaging Research Institute for Basic Science (IBS)  Suwon Republic of Korea"},{"name":"Biomedical Institute for Convergence at SKKU (BICS) Sungkyunkwan University  Suwon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0479-6195","authenticated-orcid":false,"given":"Minwoo Wendy","family":"Jang","sequence":"additional","affiliation":[{"name":"Center for Memory and Glioscience Institute for Basic Science (IBS)  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6606-1450","authenticated-orcid":false,"given":"Taeyoung","family":"Park","sequence":"additional","affiliation":[{"name":"Center for Neuroscience Imaging Research Institute for Basic Science (IBS)  Suwon Republic of Korea"},{"name":"Department of Biomedical Engineering Sungkyunkwan University  Suwon Republic of Korea"},{"name":"Department of Intelligent Precision Healthcare Convergence (IPHC) Sungkyunkwan University  Suwon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6901-3463","authenticated-orcid":false,"given":"Ki Jung","family":"Kim","sequence":"additional","affiliation":[{"name":"Center for Memory and Glioscience Institute for Basic Science (IBS)  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3832-5033","authenticated-orcid":false,"given":"Victor James","family":"Drew","sequence":"additional","affiliation":[{"name":"Center for Memory and Glioscience Institute for Basic Science (IBS)  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1817-3017","authenticated-orcid":false,"given":"Sunpil","family":"Kim","sequence":"additional","affiliation":[{"name":"Center for Memory and Glioscience Institute for Basic Science (IBS)  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8086-2476","authenticated-orcid":false,"given":"Tai Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Center for Memory and Glioscience Institute for Basic Science (IBS)  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9287-5167","authenticated-orcid":false,"given":"Mingu Gordon","family":"Park","sequence":"additional","affiliation":[{"name":"Center for Memory and Glioscience Institute for Basic Science (IBS)  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1931-4351","authenticated-orcid":false,"given":"Myeongju","family":"Kim","sequence":"additional","affiliation":[{"name":"Center for Neuroscience Imaging Research Institute for Basic Science (IBS)  Suwon Republic of Korea"},{"name":"Center for Memory and Glioscience Institute for Basic Science (IBS)  Daejeon Republic of Korea"},{"name":"Department of Biomedical Engineering Sungkyunkwan University  Suwon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9246-3692","authenticated-orcid":false,"given":"Seung Won","family":"Chung","sequence":"additional","affiliation":[{"name":"Center for Neuroscience Imaging Research Institute for Basic Science (IBS)  Suwon Republic of Korea"},{"name":"Department of Biomedical Engineering Sungkyunkwan University  Suwon Republic of Korea"},{"name":"Department of Intelligent Precision Healthcare Convergence (IPHC) Sungkyunkwan University  Suwon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1393-3550","authenticated-orcid":false,"given":"Minah","family":"Suh","sequence":"additional","affiliation":[{"name":"Center for Neuroscience Imaging Research Institute for Basic Science (IBS)  Suwon 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