Sleep intensity is adjusted by the length of previous awake time, and under tight homeostatic control by protein phosphorylation. Here, we establish microglia as a new cellular component of the sleep homeostasis circuit. Using quantitative phosphoproteomics of the mouse frontal cortex, we demonstrate that microglia-specific deletion of TNFα perturbs thousands of phosphorylation sites during the sleep period. Substrates of microglial TNFα comprise sleep-related kinases such as MAPKs and MARKs, and numerous synaptic proteins, including a subset whose phosphorylation status encodes sleep need and determines sleep duration. As a result, microglial TNFα loss attenuates the build-up of sleep need, as measured by electroencephalogram slow-wave activity and prevents immediate compensation for loss of sleep. Our data suggest that microglia control sleep homeostasis by releasing TNFα which acts on neuronal circuitry through dynamic control of phosphorylation.

中文翻译：

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小胶质细胞 TNFα 在睡眠期间协调皮质中的蛋白质磷酸化并控制稳态睡眠

睡眠强度通过之前清醒时间的长度进行调整，并受到蛋白质磷酸化的严格稳态控制。在这里，我们将小胶质细胞建立为睡眠稳态回路的新细胞成分。利用小鼠额叶皮层的定量磷酸化蛋白质组学，我们证明小胶质细胞特异性删除 TNFα 会扰乱睡眠期间的数千个磷酸化位点。小胶质细胞 TNFα 的底物包含睡眠相关激酶（例如 MAPK 和 MARK）以及许多突触蛋白，其中包括磷酸化状态编码睡眠需求并决定睡眠持续时间的子集。因此，通过脑电图慢波活动测量，小胶质细胞 TNFα 的损失会减弱睡眠需求的积累，并阻止对睡眠损失的立即补偿。我们的数据表明，小胶质细胞通过释放 TNFα 来控制睡眠稳态，TNFα 通过动态控制磷酸化作用于神经元回路。