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Astrocytes phagocytose adult hippocampal synapses for circuit homeostasis

Author

Listed:
  • Joon-Hyuk Lee

    (Korea Advanced Institute of Science and Technology (KAIST))

  • Ji-young Kim

    (Korea Brain Research Institute (KBRI)
    Daegu Gyeongbuk Institute of Science and Technology (DGIST))

  • Seulgi Noh

    (Daegu Gyeongbuk Institute of Science and Technology (DGIST)
    Korea Brain Research Institute (KBRI))

  • Hyoeun Lee

    (Korea Brain Research Institute (KBRI))

  • Se Young Lee

    (Korea Advanced Institute of Science and Technology (KAIST))

  • Ji Young Mun

    (Korea Brain Research Institute (KBRI))

  • Hyungju Park

    (Korea Brain Research Institute (KBRI)
    Daegu Gyeongbuk Institute of Science and Technology (DGIST))

  • Won-Suk Chung

    (Korea Advanced Institute of Science and Technology (KAIST))

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.

Suggested Citation

  • Joon-Hyuk Lee & Ji-young Kim & Seulgi Noh & Hyoeun Lee & Se Young Lee & Ji Young Mun & Hyungju Park & Won-Suk Chung, 2021. "Astrocytes phagocytose adult hippocampal synapses for circuit homeostasis," Nature, Nature, vol. 590(7847), pages 612-617, February.
  • Handle: RePEc:nat:nature:v:590:y:2021:i:7847:d:10.1038_s41586-020-03060-3
    DOI: 10.1038/s41586-020-03060-3
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    Cited by:

    1. Xiaojing Shi & Longlong Luo & Jixian Wang & Hui Shen & Yongfang Li & Muyassar Mamtilahun & Chang Liu & Rubing Shi & Joon-Hyuk Lee & Hengli Tian & Zhijun Zhang & Yongting Wang & Won-Suk Chung & Yaohui , 2021. "Stroke subtype-dependent synapse elimination by reactive gliosis in mice," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    2. Sruti Rayaprolu & Sara Bitarafan & Juliet V. Santiago & Ranjita Betarbet & Sydney Sunna & Lihong Cheng & Hailian Xiao & Ruth S. Nelson & Prateek Kumar & Pritha Bagchi & Duc M. Duong & Annie M. Goettem, 2022. "Cell type-specific biotin labeling in vivo resolves regional neuronal and astrocyte proteomic differences in mouse brain," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    3. Ya-Qiang Zhang & Wei-Peng Lin & Li-Ping Huang & Bing Zhao & Cheng-Cheng Zhang & Dong-Min Yin, 2021. "Dopamine D2 receptor regulates cortical synaptic pruning in rodents," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    4. Kyohei Kin & Jose Francis-Oliveira & Shin-ichi Kano & Minae Niwa, 2023. "Adolescent stress impairs postpartum social behavior via anterior insula-prelimbic pathway in mice," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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