Homer1a drives homeostatic scaling-down of excitatory synapses during sleep.
Homer1a drives homeostatic scaling-down of excitatory synapses during sleep.
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DOI：
10.1126/science.aai8355
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发表时间：
2017-02-03
期刊：
影响因子：
--
通讯作者：
Huganir RL
中科院分区：
文献类型：
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作者：
Diering GH;Nirujogi RS;Roth RH;Worley PF;Pandey A;Huganir RL
睡眠是支持学习和记忆的重要过程，它通过鲜为人知的分子机制作用于突触。通过对小鼠的生物化学、蛋白质组学和成像，我们发现在睡眠期间，突触的组成和信号发生了广泛的改变，包括突触ampa型谷氨酸受体的去除和去磷酸化导致突触减弱。这些变化是由直接早期基因Homer1a和I组代谢性谷氨酸受体mGluR1/5的信号驱动的。Homer1a作为唤醒和睡眠需求的分子整合者，分别通过去甲肾上腺素和腺苷来促进唤醒和睡眠。我们的数据表明，突触可塑性的一种全局形式——内稳态收缩在睡眠期间活跃，以重塑突触并参与情境记忆的巩固。
Sleep is an essential process that supports learning and memory by acting on synapses through poorly understood molecular mechanisms. Using biochemistry, proteomics, and imaging in mice, we find that during sleep, synapses undergo widespread alterations in composition and signaling, including weakening of synapses through removal and dephosphorylation of synaptic AMPA-type glutamate receptors. These changes are driven by the immediate early gene Homer1a and signaling from group I metabotropic glutamate receptors mGluR1/5. Homer1a serves as a molecular integrator of arousal and sleep need via the wake- and sleep-promoting neuromodulators, noradrenaline and adenosine, respectively. Our data suggest that homeostatic scaling-down, a global form of synaptic plasticity, is active during sleep to remodel synapses and participates in the consolidation of contextual memory.