Noradrenergic signaling the wakeful state inhibits microglial surveillance and synaptic plasticity in the mouse visual cortex.
Noradrenergic signaling the wakeful state inhibits microglial surveillance and synaptic plasticity in the mouse visual cortex.
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DOI：
10.1038/s41593-019-0514-0
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发表时间：
2019-09
影响因子：
25
通讯作者：
Rianne D. Stowell;Grayson O Sipe;R. Dawes;Hanna N. Batchelor;K. A. Lordy;Brendan S. Whitelaw;Mark B. Stoessel;J. Bidlack;E. Brown;M. Sur;A. Majewska
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文献类型：
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作者：
Rianne D. Stowell;Grayson O Sipe;R. Dawes;Hanna N. Batchelor;K. A. Lordy;Brendan S. Whitelaw;Mark B. Stoessel;J. Bidlack;E. Brown;M. Sur;A. Majewska
小胶质细胞是大脑的固有免疫细胞，也在突触可塑性中发挥作用。小胶质细胞过程持续地观察脑实质，与突触元件相互作用并维持组织稳态。然而，控制监视的机制及其在突触可塑性中的作用还知之甚少。体内小胶质细胞动力学主要在麻醉动物中进行研究。在这里，我们报告说，小胶质细胞的监视和损伤反应减少清醒小鼠相比，麻醉小鼠，这表明唤醒状态调节小胶质细胞的功能。β2-肾上腺素能受体的药理学刺激重现了这些观察结果，并破坏了经验依赖性可塑性，这些作用需要小胶质细胞中存在β2-肾上腺素能受体。这些结果表明，小胶质细胞在小鼠大脑中的监督和突触可塑性的作用是由去甲肾上腺素能紧张度之间的波动唤醒状态，并强调需要了解的肾上腺素能信号中断的神经发育和神经病理学的影响。
Microglia are the brain’s resident innate immune cells and also have a role in synaptic plasticity. Microglial processes continuously survey the brain parenchyma, interact with synaptic elements and maintain tissue homeostasis. However, the mechanisms that control surveillance and its role in synaptic plasticity are poorly understood. Microglial dynamics in vivo have been primarily studied in anesthetized animals. Here we report that microglial surveillance and injury response are reduced in awake mice as compared to anesthetized mice, suggesting that arousal state modulates microglial function. Pharmacologic stimulation of β2-adrenergic receptors recapitulated these observations and disrupted experience-dependent plasticity, and these effects required the presence of β2-adrenergic receptors in microglia. These results indicate that microglial roles in surveillance and synaptic plasticity in the mouse brain are modulated by noradrenergic tone fluctuations between arousal states and emphasize the need to understand the effect of disruptions of adrenergic signaling in neurodevelopment and neuropathology.