title: Optical inhibition of striatal neurons promotes focal neurogenesis and neurobehavioral recovery in mice after middle cerebral artery occlusion.
abstract: Striatal neurons regulate the activity of neural progenitor cells in the subventricular zone, but the effect of striatal neuronal activity on neurogenesis after ischemic stroke is unclear. In this study, we used optogenetic tools to investigate the impact of striatal neuronal activity on the neurogenesis and functional recovery after cerebral ischemia. We transfected striatal neurons with channelrhodopsin-2 or halorhodopsin from Natronomonas so that they can be excited by 473 nm laser or inhibited by 594 nm laser, respectively. Neural inhibition but not excitation at 4-7 days after middle cerebral artery occlusion resulted in reduced atrophy volume (6.8 ± 0.7 vs 8.5 ± 1.2 mm3, p < 0.05) and better performance represented by longer sustaining time on rotarod (99.3 ± 9 vs 80.1 ± 11 s, p < 0.01) and faster moving speed (7.7 ± 2 vs 5.7 ± 1.1 cm/s, p < 0.05) in open field tests. Furthermore, neural inhibition increased the number of nestin+, BrdU+/doublecortin+and BrdU+/NeuN+cells ( p < 0.001) in the subventricular zone and peri-focal region, and the expression level of axon guidance factor Netrin-1 (0.39 ± 0.16 vs 0.16 ± 0.02, p < 0.05) in the peri-focal region. These data suggest that striatal neuronal activity plays an important role in regulating neurogenesis and neural-behavioral outcomes, and that inhibiting striatal neurons by optogenetics promotes the recovery after ischemic stroke in mice.
authors.affiliation: 1 Department of Human Anatomy, Guangzhou Medical University, Guangzhou, China.|2 Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xiaosong
authors.initials: X
authors.lastname: He
authors.affiliation: 2 Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: 2 Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Lin
authors.affiliation: 2 Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Jiang
authors.affiliation: 2 Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yaohui
authors.initials: Y
authors.lastname: Tang
authors.affiliation: 2 Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Guanghui
authors.initials: G
authors.lastname: Tang
authors.affiliation: 2 Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Chen
authors.affiliation: 2 Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: 2 Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.|3 Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yongting
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 2 Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.|4 Shanghai Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Guo-Yuan
authors.initials: GY
authors.lastname: Yang
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000628:therapy*; D000075402:Channelrhodopsins; D025602:Halorhodopsins / Q000235:genetics / Q000528:radiation effects; D020244:Infarction, Middle Cerebral Artery; D051379:Mice; D017072:Neostriatum / Q000473:pathology*; D055495:Neurogenesis; D009474:Neurons / Q000502:physiology* / Q000528:radiation effects; D020127:Recovery of Function; D014162:Transfection
chemical_list: D000075402:Channelrhodopsins; D025602:Halorhodopsins
keywords: Brain ischemia; Netrin-1; neurogenesis; optogenetics; striatal neurons