Corticostriatal Projections Relying on GABA Levels Mediate Exercise-Induced Functional Recovery in Cerebral Ischemic Mice

谷氨酸的 神经科学 纹状体 中棘神经元 加巴能 荷包牡丹碱 黑质 光遗传学 大脑皮层 心理学 谷氨酸受体 生物 γ-氨基丁酸受体 医学 多巴胺能 多巴胺 受体 内科学 抑制性突触后电位
作者
Ying Xing,Anjing Zhang,Congqin Li,Jing Han,Jun Wang,Lu Luo,Xuechun Chang,Zhanzhuang Tian,Yulong Bai
出处
期刊:Molecular Neurobiology [Springer Science+Business Media]
卷期号:60 (4): 1836-1853 被引量:2
标识
DOI:10.1007/s12035-022-03181-y
摘要

Stroke is a neurological disorder characterized by high disability and death worldwide. The occlusion of the middle cerebral artery (MCAO) supplying the cortical motor regions and its projection pathway regions can either kill the cortical neurons or block their projections to the spinal cord and subcortical structure. The cerebral cortex is the primary striatal afferent, and the medium spiny neurons of the striatum have been identified as the major output neurons projecting to the substantia nigra and pallidum. Thus, disconnection of the corticostriatal circuit often occurs in the model of MCAO. In this study, we hypothesize that striatal network dysfunction in cerebral ischemic mice ultimately modulates the activity of striatal projections from cortical neurons to improve dysfunction during exercise training. In this study, we observed that the corticostriatal circuit originating from glutamatergic neurons could partially medicate the improvement of motor and anxiety-like behavior in mice with exercise. Furthermore, exercising or activating a single optogenetic corticostriatal circuit can increase the striatal gamma-aminobutyric acid (GABA) level. Using the GABA-A receptor antagonist, bicuculline, we further identified that the striatal glutamatergic projection from the cortical neurons relies on the GABAergic synapse's activity to modulate exercise-induced functional recovery. Overall, those results reveal that the dorsal striatum-projecting subpopulation of cortical glutamatergic neurons can influence GABA levels in the striatum, playing a critical role in modulating exercise-induced improvement of motor and anxiety-like behavior.
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