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
Affiliations
Yoshifumi Abe
Department of Neuropsychiatry, Keio University School of Medicine, Tokyo 160-8582, Japan; Live Imaging Center, Central Institute for Experimental Animals, Kawasaki 210-0821, Japan
Soojin Kwon
Department of Neuropsychiatry, Keio University School of Medicine, Tokyo 160-8582, Japan; Department of Physiology, Tohoku University School of Medicine, Sendai 980-8575, Japan
Mitsuhiro Oishi
Department of Neuropsychiatry, Keio University School of Medicine, Tokyo 160-8582, Japan
Miyuki Unekawa
Department of Neurology, Keio University School of Medicine, Tokyo 160-8582, Japan
Norio Takata
Department of Neuropsychiatry, Keio University School of Medicine, Tokyo 160-8582, Japan; Live Imaging Center, Central Institute for Experimental Animals, Kawasaki 210-0821, Japan
Fumiko Seki
Live Imaging Center, Central Institute for Experimental Animals, Kawasaki 210-0821, Japan; Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan
Ryuta Koyama
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan
Manabu Abe
Department of Animal Model Development, Brain Research Institute, Niigata University, Niigata 951-8585, Japan
Kenji Sakimura
Department of Animal Model Development, Brain Research Institute, Niigata University, Niigata 951-8585, Japan
Kazuto Masamoto
Brain Science Inspired Life Support Research Center, University of Electro-Communications, Tokyo 182-8585, Japan
Yutaka Tomita
Department of Neurology, Keio University School of Medicine, Tokyo 160-8582, Japan
Hideyuki Okano
Live Imaging Center, Central Institute for Experimental Animals, Kawasaki 210-0821, Japan; Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan; Laboratory for Marmoset Neural Architecture, RIKEN Center for Brain Science, Saitama 351-0198, Japan
Hajime Mushiake
Department of Physiology, Tohoku University School of Medicine, Sendai 980-8575, Japan
Kenji F. Tanaka
Department of Neuropsychiatry, Keio University School of Medicine, Tokyo 160-8582, Japan; Corresponding author
Summary: 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.
