Optical manipulation of local cerebral blood flow in the deep brain of freely moving mice

Yoshifumi Abe, Soojin Kwon, Mitsuhiro Oishi, Miyuki Unekawa, Norio Takata, Fumiko Seki, Ryuta Koyama, Manabu Abe, Kenji Sakimura, Kazuto Masamoto, Yutaka Tomita, Hideyuki Okano, Hajime Mushiake, Kenji F. Tanaka

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number109427
JournalCell Reports
Volume36
Issue number4
DOIs
Publication statusPublished - 2021 Jul 27

Keywords

  • cerebral blood flow
  • channelrhodopsin 2
  • Doppler
  • endothelial cell
  • fMRI
  • multi-unit activity
  • neural firing
  • optogenetics
  • photoactivated adenylyl cyclase
  • smooth muscle cell

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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