RRC ID 60833
Author Shen H, Zhu H, Panja D, Gu Q, Li Z.
Title Autophagy controls the induction and developmental decline of NMDAR-LTD through endocytic recycling.
Journal Nat Commun
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.
Volume 11(1)
Pages 2979
Published 2020-6-12
DOI 10.1038/s41467-020-16794-5
PII 10.1038/s41467-020-16794-5
PMID 32532981
PMC PMC7293213
MeSH Animals Autophagy / genetics Autophagy / physiology* Cells, Cultured Endocytosis / physiology* Hippocampus / cytology Hippocampus / metabolism Hippocampus / physiology Long-Term Synaptic Depression / physiology* Male Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Neuronal Plasticity / physiology* Neurons / metabolism Neurons / physiology Receptors, N-Methyl-D-Aspartate / metabolism* Synapses / physiology* Tissue Culture Techniques
IF 11.878
Times Cited 0
Mice RBRC02975