| RRC ID |
60833
|
| 著者 |
Shen H, Zhu H, Panja D, Gu Q, Li Z.
|
| タイトル |
Autophagy controls the induction and developmental decline of NMDAR-LTD through endocytic recycling.
|
| ジャーナル |
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.
|
| 巻・号 |
11(1)
|
| ページ |
2979
|
| 公開日 |
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
|
| 引用数 |
0
|
| リソース情報 |
| 実験動物マウス |
RBRC02975 |
