2. Academic Validation
  3. Astrocytes phagocytose adult hippocampal synapses for circuit homeostasis

Astrocytes phagocytose adult hippocampal synapses for circuit homeostasis

  • Nature. 2021 Feb;590(7847):612-617. doi: 10.1038/s41586-020-03060-3.
Joon-Hyuk Lee  # 1,  Ji-Young Kim  # 2 3,  Seulgi Noh 3 4,  Hyoeun Lee 2,  Se Young Lee 1,  Ji Young Mun 4,  Hyungju Park 5 6,  Won-Suk Chung 7
Affiliations

Affiliations

  • 1 Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
  • 2 Research Group for Neurovascular Unit, Korea Brain Research Institute (KBRI), Daegu, Republic of Korea.
  • 3 Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, Republic of Korea.
  • 4 Research Group for Neural Circuit, Korea Brain Research Institute (KBRI), Daegu, Republic of Korea.
  • 5 Research Group for Neurovascular Unit, Korea Brain Research Institute (KBRI), Daegu, Republic of Korea. phj2@kbri.re.kr.
  • 6 Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, Republic of Korea. phj2@kbri.re.kr.
  • 7 Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. wonsuk.chung@kaist.ac.kr.
  • # Contributed equally.
PMID: 33361813 DOI: 10.1038/s41586-020-03060-3
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.

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