RRC ID 76711
Author Abe Y, Kwon S, Oishi M, Unekawa M, Takata N, Seki F, Koyama R, Abe M, Sakimura K, Masamoto K, Tomita Y, Okano H, Mushiake H, Tanaka KF.
Title Optical manipulation of local cerebral blood flow in the deep brain of freely moving mice.
Journal Cell Rep
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.
Volume 36(4)
Pages 109427
Published 2021-7-27
DOI 10.1016/j.celrep.2021.109427
PII S2211-1247(21)00844-5
PMID 34320360
MeSH Animals Arterioles / metabolism Behavior, Animal Brain / blood supply* Capillaries / metabolism Cerebrovascular Circulation / physiology* Channelrhodopsins / metabolism Endothelial Cells / metabolism Mice, Inbred C57BL Movement* Myocytes, Smooth Muscle / metabolism Neurons / metabolism Optogenetics* Time Factors Venules / metabolism
IF 8.109
Mice RBRC05454