title: Cell type specificity of neurovascular coupling in cerebral cortex.
abstract: Identification of the cellular players and molecular messengers that communicate neuronal activity to the vasculature driving cerebral hemodynamics is important for (1) the basic understanding of cerebrovascular regulation and (2) interpretation of functional Magnetic Resonance Imaging (fMRI) signals. Using a combination of optogenetic stimulation and 2-photon imaging in mice, we demonstrate that selective activation of cortical excitation and inhibition elicits distinct vascular responses and identify the vasoconstrictive mechanism as Neuropeptide Y (NPY) acting on Y1 receptors. The latter implies that task-related negative Blood Oxygenation Level Dependent (BOLD) fMRI signals in the cerebral cortex under normal physiological conditions may be mainly driven by the NPY-positive inhibitory neurons. Further, the NPY-Y1 pathway may offer a potential therapeutic target in cerebrovascular disease.
authors.affiliation: Department of Radiology, University of California, San Diego, La Jolla, United States.
authors.forename: Hana
authors.initials: H
authors.lastname: Uhlirova
authors.affiliation: Department of Neurosciences, University of California, San Diego, La Jolla, United States.
authors.forename: Kıvılcım
authors.initials: K
authors.lastname: Kılıç
authors.affiliation: Department of Neurosciences, University of California, San Diego, La Jolla, United States.|Department of Physics, John Carroll University, University Heights, United States.
authors.forename: Peifang
authors.initials: P
authors.lastname: Tian
authors.affiliation: Department of Radiology, University of California, San Diego, La Jolla, United States.
authors.forename: Martin
authors.initials: M
authors.lastname: Thunemann
authors.affiliation: Department of Radiology, University of California, San Diego, La Jolla, United States.
authors.forename: Michèle
authors.initials: M
authors.lastname: Desjardins
authors.affiliation: Department of Neurosciences, University of California, San Diego, La Jolla, United States.
authors.forename: Payam A
authors.initials: PA
authors.lastname: Saisan
authors.affiliation: Martinos Center for Biomedical Imaging, Harvard Medical School, Charlestown, United States.
authors.forename: Sava
authors.initials: S
authors.lastname: Sakadžić
authors.affiliation: Department of Mathematical Sciences and Technology, Norwegian University of Life Sciences, Ås, Norway.
authors.forename: Torbjørn V
authors.initials: TV
authors.lastname: Ness
authors.affiliation: Department of Physics, University of California, San Diego, La Jolla, United States.
authors.forename: Celine
authors.initials: C
authors.lastname: Mateo
authors.affiliation: Department of Neurosciences, University of California, San Diego, La Jolla, United States.
authors.forename: Qun
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: Department of Neurosciences, University of California, San Diego, La Jolla, United States.
authors.forename: Kimberly L
authors.initials: KL
authors.lastname: Weldy
authors.affiliation: Department of Neurosciences, University of California, San Diego, La Jolla, United States.
authors.forename: Florence
authors.initials: F
authors.lastname: Razoux
authors.affiliation: Department of Radiology, University of California, San Diego, La Jolla, United States.|NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, University of Oslo, Oslo, Norway.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Vandenberghe
authors.affiliation: Biology Undergraduate Program, University of California, San Diego, La Jolla, United States.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Cremonesi
authors.affiliation: Department of Neurosciences, University of California, San Diego, La Jolla, United States.
authors.forename: Christopher Gl
authors.initials: CG
authors.lastname: Ferri
authors.affiliation: Neurosciences Graduate Program, University of California, San Diego, La Jolla, United States.
authors.forename: Krystal
authors.initials: K
authors.lastname: Nizar
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, United States.
authors.forename: Vishnu B
authors.initials: VB
authors.lastname: Sridhar
authors.affiliation: Neurosciences Graduate Program, University of California, San Diego, La Jolla, United States.
authors.forename: Tyler C
authors.initials: TC
authors.lastname: Steed
authors.affiliation: Department of Electrical and Computer Engineering, University of California, San Diego, La Jolla, United States.
authors.forename: Maxim
authors.initials: M
authors.lastname: Abashin
authors.affiliation: Department of Electrical and Computer Engineering, University of California, San Diego, La Jolla, United States.
authors.forename: Yeshaiahu
authors.initials: Y
authors.lastname: Fainman
authors.affiliation: Department of Neurosciences, University of California, San Diego, La Jolla, United States.
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
authors.affiliation: Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.|NORMENT, KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Srdjan
authors.identifier: 0000-0002-8140-8061
authors.initials: S
authors.lastname: Djurovic
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, University of Oslo, Oslo, Norway.
authors.forename: Ole A
authors.initials: OA
authors.lastname: Andreassen
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, United States.|Department of Ophthalmology, University of California, San Diego, La Jolla, United States.
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: Silva
authors.affiliation: Martinos Center for Biomedical Imaging, Harvard Medical School, Charlestown, United States.
authors.forename: David A
authors.initials: DA
authors.lastname: Boas
authors.affiliation: Department of Physics, University of California, San Diego, La Jolla, United States.|Department of Electrical and Computer Engineering, University of California, San Diego, La Jolla, United States.|Section of Neurobiology, University of California, San Diego, La Jolla, United States.
authors.forename: David
authors.initials: D
authors.lastname: Kleinfeld
authors.affiliation: Department of Radiology, University of California, San Diego, La Jolla, United States.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Buxton
authors.affiliation: Department of Mathematical Sciences and Technology, Norwegian University of Life Sciences, Ås, Norway.|Department of Physics, University of Oslo, Oslo, Norway.
authors.forename: Gaute T
authors.identifier: 0000-0002-5425-5012
authors.initials: GT
authors.lastname: Einevoll
authors.affiliation: Department of Radiology, University of California, San Diego, La Jolla, United States.|Department of Neurosciences, University of California, San Diego, La Jolla, United States.
authors.forename: Anders M
authors.initials: AM
authors.lastname: Dale
authors.affiliation: Department of Radiology, University of California, San Diego, La Jolla, United States.|Department of Neurosciences, University of California, San Diego, La Jolla, United States.|Martinos Center for Biomedical Imaging, Harvard Medical School, Charlestown, United States.
authors.forename: Anna
authors.identifier: 0000-0002-5143-3960
authors.initials: A
authors.lastname: Devor
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002561:Cerebrovascular Disorders / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D003952:Diagnostic Imaging; D015870:Gene Expression; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009478:Neuropeptide Y / Q000494:pharmacology*; D000069336:Neurovascular Coupling / Q000187:drug effects*; D062308:Optogenetics; D009928:Organ Specificity; D010100:Oxygen / Q000378:metabolism; D010775:Photic Stimulation; D011485:Protein Binding; D017476:Receptors, Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; D014662:Vasoconstrictor Agents; D010100:Oxygen
keywords: 2-photon microscopy; NPY; constriction; dilation; mouse; neuroscience; optogenetic