title: Unveiling astrocytic control of cerebral blood flow with optogenetics.
abstract: Cortical neural activities lead to changes in the cerebral blood flow (CBF), which involves astrocytic control of cerebrovascular tone. However, the manner in which astrocytic activity specifically leads to vasodilation or vasoconstriction is difficult to determine. Here, cortical astrocytes genetically expressing a light-sensitive cation channel, channelrhodopsin-2 (ChR2), were transcranially activated with a blue laser while the spatiotemporal changes in CBF were noninvasively monitored with laser speckle flowgraphy in the anesthetised mouse cortex. A brief photostimulation induced a fast transient increase in CBF. The average response onset time was 0.7 ± 0.7 sec at the activation foci, and this CBF increase spread widely from the irradiation spot with an apparent propagation speed of 0.8-1.1 mm/sec. The broad increase in the CBF could be due to a propagation of diffusible vasoactive signals derived from the stimulated astrocytes. Pharmacological manipulation showed that topical administration of a K(+) channel inhibitor (BaCl2; 0.1-0.5 mM) significantly reduced the photostimulation-induced CBF responses, which indicates that the ChR2-evoked astrocytic activity involves K(+) signalling to the vascular smooth muscle cells. These findings demonstrate a unique model for exploring the role of the astrocytes in gliovascular coupling using non-invasive, time-controlled, cell-type specific perturbations.
authors.affiliation: 1] Faculty of Informatics and Engineering, University of Electro-Communications, 1-5-1 Chofugaoka, Chofu, Tokyo 182-8585, Japan [2] Brain Science Inspired Life Support Research Centre, University of Electro-Communications, 1-5-1 Chofugaoka, Chofu, Tokyo 182-8585, Japan [3] Molecular Imaging Centre, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage, Chiba 263-8555, Japan.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Masamoto
authors.affiliation: Department of Neurology, Keio University School of Medicine, Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Unekawa
authors.affiliation: Faculty of Informatics and Engineering, University of Electro-Communications, 1-5-1 Chofugaoka, Chofu, Tokyo 182-8585, Japan.
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Neurology, Keio University School of Medicine, Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Toriumi
authors.affiliation: Molecular Imaging Centre, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage, Chiba 263-8555, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takuwa
authors.affiliation: Molecular Imaging Centre, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage, Chiba 263-8555, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawaguchi
authors.affiliation: Molecular Imaging Centre, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage, Chiba 263-8555, Japan.
authors.forename: Iwao
authors.initials: I
authors.lastname: Kanno
authors.affiliation: Department of Neuropsychiatry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
authors.forename: Ko
authors.initials: K
authors.lastname: Matsui
authors.affiliation: Division of Interdisciplinary Medical Science, Tohoku University Graduate School of Medicine, 2-1 Seiryomachi, Aoba, Sendai, Miyagi 980-8587, Japan.
authors.forename: Kenji F
authors.initials: KF
authors.lastname: Tanaka
authors.affiliation: 1] Department of Neurology, Keio University School of Medicine, Shinanomachi, Shinjuku, Tokyo 160-8582, Japan [2] Tomita Hospital, 32 Minaminakamachi, Motojuku-cho, Okazaki, Aichi 444-3505, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Tomita
authors.affiliation: Department of Neurology, Keio University School of Medicine, Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017609:Barium Compounds / Q000494:pharmacology; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D000075402:Channelrhodopsins; D002712:Chlorides / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D007213:Indomethacin / Q000494:pharmacology; D007834:Lasers; D055537:Light Signal Transduction; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D062308:Optogenetics / Q000379:methods*; D010775:Photic Stimulation; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D019076:Transgenes; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D017609:Barium Compounds; D000075402:Channelrhodopsins; D002712:Chlorides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C024986:barium chloride; D013779:Tetrodotoxin; D007213:Indomethacin