Cited 28 time in webofscience Cited 27 time in scopus

Astrocytes phagocytose adult hippocampal synapses for circuit homeostasis

Title
Astrocytes phagocytose adult hippocampal synapses for circuit homeostasis
Authors
Lee, Joon-HyukKim, Ji-youngNoh, SeulgiLee, HyoeunLee, Se YoungMun, Ji YoungPark, HyungjuChung, Won-Suk
DGIST Authors
Lee, Joon-Hyuk; Kim, Ji-young; Noh, Seulgi; Lee, Hyoeun; Lee, Se Young; Mun, Ji Young; Park, Hyungju; Chung, Won-Suk
Issue Date
2021-02
Citation
Nature, 590(7847), 612-617
Type
Article
Article Type
Article; Early Access
Keywords
MICROGLIAPOOLELIMINATIONPLASTICITY
ISSN
0028-0836
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. © 2020, The Author(s), under exclusive licence to Springer Nature Limited.
URI
http://hdl.handle.net/20.500.11750/12766
DOI
10.1038/s41586-020-03060-3
Publisher
Nature Publishing Group
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