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星形胶质细胞通过吞噬成人海马体神经突触稳定脑电路
2020-12-25 15:05

2020年12月23日出版的《自然》杂志在线发表了韩国科学技术高等研究院Won-Suk Chung和韩国脑科学研究所Hyungju Park团队合作的最新研究成果。他们发现星形胶质细胞通过吞噬成人海马神经突触来稳定电路。

在本研究中,研究人员发现星形胶质细胞的吞噬作用对于维持正常海马体突触的连接性和可塑性至关重要。通过使用荧光标记吞噬报告基因,研究发现,成年小鼠海马CA1区的神经胶质吞噬作用消除了兴奋性和抑制性突触。出乎意料的是,研究人员发现星形胶质细胞在神经元活动依赖的兴奋性突触消除中起主要作用。

此外,星形胶质细胞吞噬受体MEGF10缺失的小鼠表现出兴奋性突触消除减少,从而导致过多功能受损突触的累积。最后,Megf10基因敲除小鼠表现出长期突触可塑性缺陷和海马记忆形成受损。总的来说,该研究数据提供的有力证据表明星形胶质细胞通过MEGF10消除了成年海马体中不必要的兴奋性突触连接,并且星形细胞的这种功能对于维持电路连通性和认知功能至关重要。

据介绍,在成年海马体中不断发生突触的形成和清除。但是,尚不清楚成年大脑中突触消除的确切功能及其调控方式。

附:英文原文

Title: Astrocytes phagocytose adult hippocampal synapses for circuit homeostasis

Author: Joon-Hyuk Lee, Ji-young Kim, Seulgi Noh, Hyoeun Lee, Se Young Lee, Ji Young Mun, Hyungju Park, Won-Suk Chung

Issue&Volume: 2020-12-23

Abstract: In the adult hippocampus, synapses are constantly formed and eliminated1,2. However, the exact function of synapse elimination in the adult brain, and how it is regulated, are largely unknown. Here we show that astrocytic phagocytosis3 is important for maintaining proper hippocampal synaptic connectivity and plasticity. By using fluorescent phagocytosis reporters, we find that excitatory and inhibitory synapses are eliminated by glial phagocytosis in the CA1 region of the adult mouse hippocampus. Unexpectedly, we found that astrocytes have a major role in the neuronal activity-dependent elimination of excitatory synapses. Furthermore, mice in which astrocytes lack the phagocytic receptor MEGF10 show a reduction in the elimination of excitatory synapses; as a result, excessive but functionally impaired synapses accumulate. Finally, Megf10-knockout mice show defective long-term synaptic plasticity and impaired formation of hippocampal memories. Together, our data provide strong evidence that astrocytes eliminate unnecessary excitatory synaptic connections in the adult hippocampus through MEGF10, and that this astrocytic function is crucial for maintaining circuit connectivity and thereby supporting cognitive function. In adult mice, astrocytes carry out phagocytosis of excitatory hippocampal synapses through MEGF10 to maintain synaptic and circuit homeostasis.

DOI: 10.1038/s41586-020-03060-3

Source: https://www.nature.com/articles/s41586-020-03060-3

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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