英国牛津大学Colin J. Akerman和Hannah Alfonsa共同合作，近期取得重要工作进展。他们研究发现细胞内氯离子可以调节介导大脑皮层的局部睡眠压力。相关研究成果2022年12月12日在线发表于《自然—神经科学》杂志上。

据介绍，长时间的清醒与工作表现下降和睡眠压力增加有关。在大脑皮层中，这表现为网络活动的变化。这些变化取决于清醒时的体验，它们的潜在机制代表了克服疲劳影响的目标。

研究人员揭示了细胞内氯离子调节的核心作用，它通过皮层锥体神经元中的GABA_A受体来设定突触后抑制的强度。清醒导致GABA_A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，并涉及氯化物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。

总之，这些发现表明，氯化物调节是睡眠-觉醒史、皮层活动和行为之间的一个关键环节。

附：英文原文

Title: Intracellular chloride regulation mediates local sleep pressure in the cortex

Author: Alfonsa, Hannah, Burman, Richard J., Brodersen, Paul J. N., Newey, Sarah E., Mahfooz, Kashif, Yamagata, Tomoko, Panayi, Marios C., Bannerman, David M., Vyazovskiy, Vladyslav V., Akerman, Colin J.

Issue&Volume: 2022-12-12

Abstract: 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.

DOI: 10.1038/s41593-022-01214-2

Source: https://www.nature.com/articles/s41593-022-01214-2