Optical manipulation of local cerebral blood flow in the deep brain of freely moving mice.
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
Doppler
cerebral blood flow
channelrhodopsin 2
endothelial cell
fMRI
multi-unit activity
neural firing
optogenetics
photoactivated adenylyl cyclase
smooth muscle cell
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
27 07 2021
27 07 2021
Historique:
received:
07
05
2020
revised:
07
06
2021
accepted:
29
06
2021
entrez:
28
7
2021
pubmed:
29
7
2021
medline:
10
2
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34320360
pii: S2211-1247(21)00844-5
doi: 10.1016/j.celrep.2021.109427
pii:
doi:
Substances chimiques
Channelrhodopsins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
109427Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests H.O. is a founding scientist and a paid scientific advisor of SanBio and K Pharma. The other authors declare no competing interests.