Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, University of Copenhagen, 2200, Copenhagen, Denmark.
Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY, 14642, USA.
Nat Commun. 2023 Apr 4;14(1):1871. doi: 10.1038/s41467-023-37433-9.
Information transfer within neuronal circuits depends on the balance and recurrent activity of excitatory and inhibitory neurotransmission. Chloride (Cl) is the major central nervous system (CNS) anion mediating inhibitory neurotransmission. Astrocytes are key homoeostatic glial cells populating the CNS, although the role of these cells in regulating excitatory-inhibitory balance remains unexplored. Here we show that astrocytes act as a dynamic Cl reservoir regulating Cl homoeostasis in the CNS. We found that intracellular chloride concentration ([Cl]) in astrocytes is high and stable during sleep. In awake mice astrocytic [Cl] is lower and exhibits large fluctuation in response to both sensory input and motor activity. Optogenetic manipulation of astrocytic [Cl] directly modulates neuronal activity during locomotion or whisker stimulation. Astrocytes thus serve as a dynamic source of extracellular Cl available for GABAergic transmission in awake mice, which represents a mechanism for modulation of the inhibitory tone during sustained neuronal activity.
神经元回路中的信息传递依赖于兴奋性和抑制性神经递质传递的平衡和反复活动。氯离子 (Cl) 是介导抑制性神经递质传递的主要中枢神经系统 (CNS) 阴离子。星形胶质细胞是中枢神经系统中主要的同型胶质细胞，尽管这些细胞在调节兴奋-抑制平衡方面的作用仍未被探索。在这里，我们表明星形胶质细胞作为一个动态的 Cl 库，调节中枢神经系统中的 Cl 同型平衡。我们发现星形胶质细胞内的氯离子浓度 ([Cl]) 在睡眠期间较高且稳定。在清醒的小鼠中，星形胶质细胞内的 [Cl] 较低，并对感觉输入和运动活动表现出较大的波动。光遗传学操纵星形胶质细胞内的 [Cl] 直接调节运动或胡须刺激时的神经元活动。因此，星形胶质细胞在清醒的小鼠中充当细胞外 Cl 的动态来源，用于 GABA 能传递，这代表了在持续神经元活动期间调节抑制性音调的一种机制。
