Astrocytes produce and supply metabolic substrates to neurons through gap junction-mediated astroglial networks. However, the role of astroglial metabolic networks in behavior is unclear. Here, we demonstrate that perturbation of astroglial networks impairs the sleep-wake cycle. Using a conditional Cre-Lox system in mice, we show that knockout of the gap junction subunit connexin 43 in astrocytes throughout the brain causes excessive sleepiness and fragmented wakefulness during the nocturnal active phase. This astrocyte-specific genetic manipulation silenced the wake-promoting orexin neurons located in the lateral hypothalamic area (LHA) by impairing glucose and lactate trafficking through astrocytic networks. This global wakefulness instability was mimicked with viral delivery of Cre recombinase to astrocytes in the LHA and rescued by in vivo injections of lactate. Our findings propose a novel regulatory mechanism critical for maintaining normal daily cycle of wakefulness and involving astrocyte-neuron metabolic interactions.

中文翻译：

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连接蛋白43介导的星形胶质代谢网络有助于调节睡眠-唤醒循环。

星形胶质细胞通过间隙连接介导的星形胶质网络产生并向神经元提供代谢底物。但是，星形胶质代谢网络在行为中的作用尚不清楚。在这里，我们证明了星形胶质网络的扰动会损害睡眠-觉醒周期。使用小鼠中的条件性Cre-Lox系统，我们显示出在整个夜间星形细胞中，星形胶质细胞中的间隙连接亚基连接蛋白43的敲除会导致过度的嗜睡和觉醒。这种星形胶质细胞特异性的遗传操作通过损害通过星形胶质网络的葡萄糖和乳酸的运输，使位于下丘脑外侧区域（LHA）的促醒食欲素神经元沉默。通过将Cre重组酶病毒递送至LHA中的星形胶质细胞，可以模拟这种整体的觉醒不稳定性，并通过体内注射乳酸来挽救。我们的发现提出了一种新的调节机制，对于维持正常的日常清醒周期和涉及星形胶质细胞-神经元代谢相互作用至关重要。