Department of Neuropsychiatry, Keio University School of Medicine, Tokyo 160-8582, Japan; Live Imaging Center, Central Institute for Experimental Animals, Kawasaki 210-0821, Japan.
Department of Neuropsychiatry, Keio University School of Medicine, Tokyo 160-8582, Japan; Department of Physiology, Tohoku University School of Medicine, Sendai 980-8575, Japan.
Cell Rep. 2021 Jul 27;36(4):109427. doi: 10.1016/j.celrep.2021.109427.
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.
一种用于操纵局部脑血流 (CBF) 的人工工具对于理解 CBF 如何控制大脑功能是必要的。在这里，我们生成血管光遗传学工具，使平滑肌细胞和内皮细胞在大脑中表达光学驱动器。表达通道视紫红质-2 (ChR2) 的小鼠的光照会导致局部 CBF 降低。光激活的腺苷酸环化酶 (PAC) 是一种光学蛋白，可增加细胞内环磷酸腺苷 (cAMP)，表达 PAC 的小鼠的光照会导致局部 CBF 增加。我们以腹侧纹状体为靶点，确定 CBF 变化的时间动力学，并优化光照强度将作用局限于腹侧纹状体。我们在自由和自适应行为的小鼠中证明了这种血管光遗传学操作的实用性，并验证了任务和驱动器相关的行为结果。血管光遗传学动物模型的发展将有助于加速研究血管、回路和行为与健康和疾病的联系。
