Optical manipulation of local cerebral blood flow in the deep brain of freely moving mice
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 chan...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-07-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124721008445 |
| _version_ | 1818643214161149952 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Yoshifumi Abe |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-16T23:55:24Z |
| format | Article |
| id | doaj.art-530c34d3c03248d6abed02a32d2771c5 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-16T23:55:24Z |
| publishDate | 2021-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-530c34d3c03248d6abed02a32d2771c52022-12-21T22:11:13ZengElsevierCell Reports2211-12472021-07-01364109427Optical manipulation of local cerebral blood flow in the deep brain of freely moving miceYoshifumi Abe0Soojin Kwon1Mitsuhiro Oishi2Miyuki Unekawa3Norio Takata4Fumiko Seki5Ryuta Koyama6Manabu Abe7Kenji Sakimura8Kazuto Masamoto9Yutaka Tomita10Hideyuki Okano11Hajime Mushiake12Kenji F. Tanaka13Department of Neuropsychiatry, Keio University School of Medicine, Tokyo 160-8582, Japan; Live Imaging Center, Central Institute for Experimental Animals, Kawasaki 210-0821, JapanDepartment of Neuropsychiatry, Keio University School of Medicine, Tokyo 160-8582, Japan; Department of Physiology, Tohoku University School of Medicine, Sendai 980-8575, JapanDepartment of Neuropsychiatry, Keio University School of Medicine, Tokyo 160-8582, JapanDepartment of Neurology, Keio University School of Medicine, Tokyo 160-8582, JapanDepartment of Neuropsychiatry, Keio University School of Medicine, Tokyo 160-8582, Japan; Live Imaging Center, Central Institute for Experimental Animals, Kawasaki 210-0821, JapanLive Imaging Center, Central Institute for Experimental Animals, Kawasaki 210-0821, Japan; Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, JapanLaboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, JapanDepartment of Animal Model Development, Brain Research Institute, Niigata University, Niigata 951-8585, JapanDepartment of Animal Model Development, Brain Research Institute, Niigata University, Niigata 951-8585, JapanBrain Science Inspired Life Support Research Center, University of Electro-Communications, Tokyo 182-8585, JapanDepartment of Neurology, Keio University School of Medicine, Tokyo 160-8582, JapanLive 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, JapanDepartment of Physiology, Tohoku University School of Medicine, Sendai 980-8575, JapanDepartment of Neuropsychiatry, Keio University School of Medicine, Tokyo 160-8582, Japan; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124721008445optogeneticscerebral blood flowsmooth muscle cellendothelial cellchannelrhodopsin 2photoactivated adenylyl cyclase |
| spellingShingle | 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 Optical manipulation of local cerebral blood flow in the deep brain of freely moving mice Cell Reports optogenetics cerebral blood flow smooth muscle cell endothelial cell channelrhodopsin 2 photoactivated adenylyl cyclase |
| title | Optical manipulation of local cerebral blood flow in the deep brain of freely moving mice |
| title_full | Optical manipulation of local cerebral blood flow in the deep brain of freely moving mice |
| title_fullStr | Optical manipulation of local cerebral blood flow in the deep brain of freely moving mice |
| title_full_unstemmed | Optical manipulation of local cerebral blood flow in the deep brain of freely moving mice |
| title_short | Optical manipulation of local cerebral blood flow in the deep brain of freely moving mice |
| title_sort | optical manipulation of local cerebral blood flow in the deep brain of freely moving mice |
| topic | optogenetics cerebral blood flow smooth muscle cell endothelial cell channelrhodopsin 2 photoactivated adenylyl cyclase |
| url | http://www.sciencedirect.com/science/article/pii/S2211124721008445 |
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