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We engineered adeno-associated viral vectors (AAVs) to express a bacterial photoactivated adenylyl cyclase in astrocytes, which triggers an increase in cAMP upon blue light stimulation. Opto-stimulation also elevated astrocytic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    , albeit with a delayed onset under mild stimulation. In vivo imaging of anesthetized and awake wild-type mice through a thinned skull preparation revealed that optogenetically induced astrocytic cAMP elevation led to pronounced arteriole dilation, with a latency of 1.8 s and maximal dilation reached within 10 s in the awake state and slower response under anesthesia. Mild opto-stimulation causing sensory-level cAMP elevations was sufficient to induce arteriole dilation. This effect was preserved in IP\n                    <jats:sub>3<\/jats:sub>\n                    receptor type 2-knockout (IP\n                    <jats:sub>3<\/jats:sub>\n                    R2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) mice, indicating a mechanism independent of GPCR-induced intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    elevations. These findings highlight astrocytic cAMP as a key modulator of cerebral vasodilation, contributing to our understanding of local CBF regulation. This study opens broad avenues for understanding astrocyte-mediated control of CBF and its implications in neurological diseases characterized by dysregulated blood flow.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2422069122","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T13:54:41Z","timestamp":1756994081000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":19,"title":["Cerebral blood flow is modulated by astrocytic cAMP elevation independently of IP\n                    <sub>3<\/sub>\n                    R2-mediated Ca\n                    <sup>2+<\/sup>\n                    signaling in mice"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5155-5917","authenticated-orcid":false,"given":"Marta","family":"Vittani","sequence":"first","affiliation":[{"name":"Center for Translational Neuromedicine, Faculty of Health and Life Sciences, University of 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