近日，南方医科大学任思强及其小组的论文发现了轴突初始节段相关的小胶质细胞调节神经元活动和视觉感知。相关论文于2026年1月28日发表在《细胞研究》杂志上。

研究组发现了一种特殊的新皮质小胶质细胞，它与兴奋性神经元的轴突初始段（AISs）特异性相关，可以调节它们的活动并参与视觉感知。该课题组发现AIS相关小胶质细胞的短暂去极化，而非AIS相关小胶质细胞的去极化，显著促进了相关兴奋性神经元的动作电位放电，其机制依赖于小胶质细胞通过向外K⁺通道thk -1释放K⁺。有趣的是，用漂移光栅进行的体内视觉刺激在特定的过程中诱发了小胶质细胞的瞬态去极化，这一过程依赖于毒蕈碱受体，并通过THIK-1触发K⁺释放；与此同时，视觉刺激诱导的与小胶质细胞相关的神经元在其AIS处的钙离子反应比附近的非相关神经元更多。AIS-小胶质细胞相互作用的破坏干扰了与AIS相关的神经元的钙反应，损害了整个神经系统的协调活动，从而影响了清醒小鼠的视觉辨别行为。总的来说，他们的发现确定了一种新型的小胶质细胞-神经元功能相互作用，这种相互作用可能对高阶大脑功能至关重要。

据悉，小胶质细胞作为大脑中的先天免疫细胞，直接接触兴奋性神经元，并在各种条件下调节其活动；然而，直接的小胶质细胞-神经元功能相互作用的机制在很大程度上仍然未知。

附：英文原文

Title: The axon initial segment-associated microglia regulate neuronal activity and visual perception

Author: Wang, Yaping, Wang, Qiushi, Gao, Chen, He, Shu, Wei, Cheng, Song, Jia, Liu, Xinli, Liu, Xiaoli, Feng, Shi, Yao, Wen, Wu, Wen, Gao, Tian-Ming, Ren, Siqiang

Issue&Volume: 2026-01-28

Abstract: As innate immune cells in the brain, microglia directly contact excitatory neurons and regulate their activities under various conditions; however, the mechanisms of direct microglia–neuron functional interactions remain largely unknown. Here, we identified one special population of neocortical microglia that specifically associate with the axon initial segments (AISs) of excitatory neurons, and could regulate their activities and contribute to visual perception. We found that brief depolarization of AIS-associated microglia, but not the AIS-non-associated microglia, significantly promoted the action potential firing of related excitatory neurons, which relied mechanistically on microglial K+ release through the outward K+ channel THIK-1. Interestingly, in vivo visual stimulation with drifting gratings evoked microglial transient depolarizations specifically on the processes, which depended on muscarinic receptors and triggered K+ release through THIK-1; meanwhile, visual stimulation induced more robust calcium responses in neurons associated with microglia at their AISs compared with nearby unassociated neurons. Disruption of the AIS–microglia interaction disturbed calcium responses specifically in neurons associated with microglia at their AISs, impaired the coordinated activity of the entire neural ensemble, and thereby affected the visual discrimination behavior of awake mice. Collectively, our findings identified a new type of microglia–neuron functional interaction that may be critical for higher-order brain functions.

DOI: 10.1038/s41422-026-01218-8

Source: https://www.nature.com/articles/s41422-026-01218-8