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Adv."],"published-print":{"date-parts":[[2026,7,3]]},"abstract":"<jats:p>\n                    Neuronal activity\u2013driven increases in cerebral blood flow (CBF), known as neurovascular coupling (NVC), are crucial for sustaining the metabolic demands of the brain. Our group has found that Tacr1 neurons, a subset of somatostatin neurons expressing the substance P (SP) receptor and neuronal nitric oxide synthase (nNOS), exert a disproportionately large regulation of CBF. Here, we use two-photon imaging to show that Tacr1 neurons regulate CBF through nitric oxide (NO) release and SP-receptor signaling . We identify astrocytic calcium (Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ) transients as a secondary response to vasodilation. To identify potential sources of SP in somatosensory cortex, viral mapping revealed\n                    <jats:italic toggle=\"yes\">Tac1<\/jats:italic>\n                    -positive neurons locally, predominantly among parvalbumin (PV) neurons, as well as\n                    <jats:italic toggle=\"yes\">Tac1<\/jats:italic>\n                    -positive long-range projections from perirhinal cortex. Functional analyses indicate that PV neurons regulate CBF through a Tacr1 neuron dependent pathway. These findings suggest a sequential mechanism whereby Tacr1 neurons respond to SP to release NO, inducing vasodilation and driving astrocytic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adx5109","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T17:58:28Z","timestamp":1783101508000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Substance P regulates Tacr1 neurons, which control nitric oxide\u2013mediated neurovascular coupling in the mouse cortex"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2399-0687","authenticated-orcid":true,"given":"Fernanda","family":"Juarez Anaya","sequence":"first","affiliation":[{"name":"Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1668-1273","authenticated-orcid":true,"given":"Jiwon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2593-3133","authenticated-orcid":true,"given":"Sarah E.","family":"Ross","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, USA."},{"name":"Department of Anesthesiology, University of Pittsburgh, Pittsburgh, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5105-9825","authenticated-orcid":true,"given":"Alberto L.","family":"Vazquez","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA."},{"name":"Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09613"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X17740091"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.08.019"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncom.2019.00049"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature17965"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09108"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0651-15.2015"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2133652100"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.07.030"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11934"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00966.2005"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.01.003"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.120178897"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1387"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-021-00904-7"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X19870105"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhz251"},{"key":"e_1_3_2_19_2","first-page":"H1085","article-title":"Regional cerebral blood flow response to vibrissal stimulation in mice lacking type I NOS gene expression","volume":"270","author":"Ma J.","year":"1996","unstructured":"J. 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