美国梅奥诊所神经内科Long-Jun Wu课题组发现，小胶质细胞通过屏蔽抑制性突触增强麻醉后神经元活动。相关论文于2024年1月4日发表在《自然—神经科学》杂志上。

利用小鼠体内双光子成像，他们发现小胶质细胞在异氟醚麻醉停止后增强了神经元活动。过度活跃的神经元体与小胶质突起直接联系，而小胶质突起与GABA能钮扣特异性地共定位。双光子成像后基于电子显微镜的突触重建显示，在麻醉期间，小胶质过程进入突触间隙以屏蔽GABA能输入。小胶质消融或小胶质β2-肾上腺素能受体的丧失可防止麻醉后神经元的过度活跃。

他们的研究证明了小胶质细胞过程动力学的一个以前未被认识到的功能，它使小胶质细胞能够通过物理屏蔽抑制输入来短暂地促进麻醉后的神经元活动。

据悉，小胶质细胞是中枢神经系统的常驻免疫细胞，在大脑稳态中起着关键作用。在麻醉过程中，小胶质细胞增强了对动态过程的监控，与神经元的相互作用更加密切。然而，麻醉下小胶质过程动力学和神经元相互作用的功能意义在很大程度上是未知的。

附：英文原文

Title: Microglia enhance post-anesthesia neuronal activity by shielding inhibitory synapses

Author: Haruwaka, Koichiro, Ying, Yanlu, Liang, Yue, Umpierre, Anthony D., Yi, Min-Hee, Kremen, Vaclav, Chen, Tingjun, Xie, Tao, Qi, Fangfang, Zhao, Shunyi, Zheng, Jiaying, Liu, Yong U., Dong, Hailong, Worrell, Gregory A., Wu, Long-Jun

Issue&Volume: 2024-01-04

Abstract: Microglia are resident immune cells of the central nervous system and play key roles in brain homeostasis. During anesthesia, microglia increase their dynamic process surveillance and interact more closely with neurons. However, the functional significance of microglial process dynamics and neuronal interaction under anesthesia is largely unknown. Using in vivo two-photon imaging in mice, we show that microglia enhance neuronal activity after the cessation of isoflurane anesthesia. Hyperactive neuron somata are contacted directly by microglial processes, which specifically colocalize with GABAergic boutons. Electron-microscopy-based synaptic reconstruction after two-photon imaging reveals that, during anesthesia, microglial processes enter into the synaptic cleft to shield GABAergic inputs. Microglial ablation or loss of microglial β2-adrenergic receptors prevents post-anesthesia neuronal hyperactivity. Our study demonstrates a previously unappreciated function of microglial process dynamics, which enable microglia to transiently boost post-anesthesia neuronal activity by physically shielding inhibitory inputs.

DOI: 10.1038/s41593-023-01537-8

Source: https://www.nature.com/articles/s41593-023-01537-8