@article{009bb2451c8a479f8299eae23e22898b,
title = "Optical manipulation of local cerebral blood flow in the deep brain of freely moving mice",
abstract = "An artificial tool for manipulating local cerebral blood flow (CBF) is necessary for understanding how CBF controls brain function. Here, we generate vascular optogenetic tools whereby smooth muscle cells and endothelial cells express optical actuators in the brain. The illumination of channelrhodopsin-2 (ChR2)-expressing mice induces a local reduction in CBF. Photoactivated adenylyl cyclase (PAC) is an optical protein that increases intracellular cyclic adenosine monophosphate (cAMP), and the illumination of PAC-expressing mice induces a local increase in CBF. We target the ventral striatum, determine the temporal kinetics of CBF change, and optimize the illumination intensity to confine the effects to the ventral striatum. We demonstrate the utility of this vascular optogenetic manipulation in freely and adaptively behaving mice and validate the task- and actuator-dependent behavioral readouts. The development of vascular optogenetic animal models will help accelerate research linking vasculature, circuits, and behavior to health and disease.",
keywords = "Doppler, cerebral blood flow, channelrhodopsin 2, endothelial cell, fMRI, multi-unit activity, neural firing, optogenetics, photoactivated adenylyl cyclase, smooth muscle cell",
author = "Yoshifumi Abe and Soojin Kwon and Mitsuhiro Oishi and Miyuki Unekawa and Norio Takata and Fumiko Seki and Ryuta Koyama and Manabu Abe and Kenji Sakimura and Kazuto Masamoto and Yutaka Tomita and Hideyuki Okano and Hajime Mushiake and Tanaka, {Kenji F.}",
note = "Funding Information: The authors would like to thank Chihoko Yamada for the animal support in the MRI study. This work was supported by a grant-in-aid from the Japan Society for the Promotion of Science (JSPS) under grant nos. 18J00922 (to Y.A.), 19K16298 (to Y.A.), 19K06944 (to N.T.), JP16H06276 (to H.M.), and 19H03337 (to H.M.); a grant-in-aid for Transformative Research Areas (A) {\textquoteleft}Glial Decoding{\textquoteright} under grant no. 20H05896 (to K.F.T.); a grant from Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) by AMED under grant nos. JP21dm0207069 (to K.F.T.) and JP21dm0207001 (H.O.); and a grant-in-aid from the Keio University Program for the Advancement of Next Generation Research Projects (to M.U., Y.T., and K.F.T), the Takeda Science Foundation (to Y.A.), and MEXT KAKENHI (Non-linear Neuro-oscillology) under grant no. 15H05879 (to H.M.). Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = jul,
day = "27",
doi = "10.1016/j.celrep.2021.109427",
language = "English",
volume = "36",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "4",
}