Nat Neurosci—细胞内氯离子调控皮层睡眠压力

中文摘要

长时间的清醒与工作表现下降和睡眠压力增加有关。在大脑皮层，这表现为网络活动的变化。网络活动变化往往表现出局部差异，这取决于清醒时的体验，其潜在机制代表了克服疲劳效应的目标。在这里，科学家揭示了细胞内氯离子在调节睡眠压力中的关键作用，细胞内氯离子通过皮层锥体神经元中的GABAA受体来设定突触后抑制的强度。觉醒会导致GABAA受体平衡电位的去极化变化，反映了清醒时的局部活动依赖性过程，并涉及氯离子协同转运蛋白活性的变化。这些变化是皮层内局部睡眠压力的电生理和行为标志物的基础，包括非快速眼动睡眠期间的慢波活动水平、低频振荡活动水平以及睡眠剥夺清醒状态下的表现水平降低。这些发现表明，氯离子调节机制是睡眠觉醒史、皮层活动和行为之间的关键联系。

英文摘要

Extended wakefulness is associated with reduced performance and the build-up of sleep pressure. In the cortex, this manifests as changes in network activity. These changes show local variation depending on the waking experience, and their underlying mechanisms represent targets for overcoming the effects of tiredness. Here, we reveal a central role for intracellular chloride regulation, which sets the strength of postsynaptic inhibition via GABAA receptors in cortical pyramidal neurons. Wakefulness results in depolarizing shifts in the equilibrium potential for GABAA receptors, reflecting local activity-dependent processes during waking and involving changes in chloride cotransporter activity. These changes underlie electrophysiological and behavioral markers of local sleep pressure within the cortex, including the levels of slow-wave activity during non-rapid eye movement sleep and low-frequency oscillatory activity and reduced performance levels in the sleep-deprived awake state. These findings identify chloride regulation as a crucial link between sleep-wake history, cortical activity and behavior.

参考文献：Intracellular chloride regulation mediates local sleep pressure in the cortex. Nat Neurosci. 2022 Dec 12. doi: 10.1038/s41593-022-01214-2. Online ahead of print.

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