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Autophagy controls the induction and developmental decline of NMDAR-LTD through endocytic recycling

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  • Hongmei Shen

    (National Institute of Mental Health, National Institutes of Health
    Nantong University
    Nantong University)

  • Huiwen Zhu

    (National Institute of Mental Health, National Institutes of Health)

  • Debabrata Panja

    (National Institute of Mental Health, National Institutes of Health)

  • Qinhua Gu

    (National Institute of Mental Health, National Institutes of Health)

  • Zheng Li

    (National Institute of Mental Health, National Institutes of Health)

Abstract

NMDA receptor-dependent long-term depression (NMDAR-LTD) is a long-lasting form of synaptic plasticity. Its expression is mediated by the removal of AMPA receptors from postsynaptic membranes. Under basal conditions, endocytosed AMPA receptors are rapidly recycled back to the plasma membrane. In NMDAR-LTD, however, they are diverted to late endosomes for degradation. The mechanism for this switch is largely unclear. Additionally, the inducibility of NMDAR-LTD is greatly reduced in adulthood. The underlying mechanism and physiological significance of this phenomenon are elusive. Here, we report that autophagy inhibition is essential for the induction and developmental dampening of NMDAR-LTD. Autophagy is inhibited during NMDAR-LTD to decrease endocytic recycling. Autophagy inhibition is both necessary and sufficient for LTD induction. In adulthood, autophagy is up-regulated to make LTD induction harder, thereby preventing the adverse effect of excessive LTD on memory consolidation. These findings reveal the unrecognized functions of autophagy in synaptic plasticity, endocytic recycling, and memory.

Suggested Citation

  • Hongmei Shen & Huiwen Zhu & Debabrata Panja & Qinhua Gu & Zheng Li, 2020. "Autophagy controls the induction and developmental decline of NMDAR-LTD through endocytic recycling," Nature Communications, Nature, vol. 11(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16794-5
    DOI: 10.1038/s41467-020-16794-5
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    Cited by:

    1. Emmanouela Kallergi & Akrivi-Dimitra Daskalaki & Angeliki Kolaxi & Come Camus & Evangelia Ioannou & Valentina Mercaldo & Per Haberkant & Frank Stein & Kyriaki Sidiropoulou & Yannis Dalezios & Mikhail , 2022. "Dendritic autophagy degrades postsynaptic proteins and is required for long-term synaptic depression in mice," Nature Communications, Nature, vol. 13(1), pages 1-23, December.

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