Neuronal activity drives pathway-specific depolarization of peripheral astrocyte processes.
Neuronal activity drives pathway-specific depolarization of peripheral astrocyte processes.
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DOI：
10.1038/s41593-022-01049-x
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发表时间：
2022-05
影响因子：
25
通讯作者：
Dulla, Chris G.
中科院分区：
文献类型：
--
作者：
Armbruster, Moritz;Naskar, Saptarnab;Garcia, Jacqueline;Sommer, Mary;Kim, Elliot;Adam, Yoav;Haydon, Philip G.;Boyden, Edward S.;Cohen, Adam E.;Dulla, Chris G.
星形胶质细胞是通过其远端突起与神经元突触相互作用的神经胶质细胞，其中它们在神经元活动后从细胞外空间去除谷氨酸和钾（K+）。星形胶质细胞对谷氨酸和K+的清除是电压依赖性的，但星形胶质细胞膜电位（Vm）被认为在很大程度上是不变的。因此，这些电压依赖性被认为与星形胶质细胞功能无关。使用基因编码的电压指标，使Vm在小鼠外周星形胶质细胞过程（PAP）的测量，我们报告大，快速，局灶性和特定的路径在PAP神经元活动的去极化。这些活性依赖性星形胶质细胞去极化是由动作电位介导的突触前K+流出和产电谷氨酸转运蛋白驱动的。我们发现，PAP去极化抑制神经元活动过程中星形胶质细胞谷氨酸清除，增强谷氨酸激活神经元。这代表了一类新的亚细胞星形胶质细胞膜动力学和星形胶质细胞-神经元相互作用的新形式。
Astrocytes are glial cells that interact with neuronal synapses via their distal processes, where they remove glutamate and potassium (K+) from the extracellular space following neuronal activity. Astrocyte clearance of both glutamate and K+ is voltage-dependent, but astrocyte membrane potential (Vm) has been thought to be largely invariant. As a result, these voltage-dependencies have not been considered relevant to astrocyte function. Using genetically encoded voltage indicators to enable the measurement of Vm at peripheral astrocyte processes (PAPs) in mice, we report large, rapid, focal, and pathway-specific depolarizations in PAPs during neuronal activity. These activity-dependent astrocyte depolarizations are driven by action potential-mediated presynaptic K+ efflux and electrogenic glutamate transporters. We find that PAP depolarization inhibits astrocyte glutamate clearance during neuronal activity, enhancing neuronal activation by glutamate. This represents a novel class of sub-cellular astrocyte membrane dynamics and a new form of astrocyte-neuron interaction.
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影响因子：
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