NMDAR-dependent long-term depression is associated with increased short term plasticity through autophagy mediated loss of PSD-95.
Nat Commun
; 12(1): 2849, 2021 05 14.
Article
in En
| MEDLINE
| ID: mdl-33990590
ABSTRACT
Long-term depression (LTD) of synaptic strength can take multiple forms and contribute to circuit remodeling, memory encoding or erasure. The generic term LTD encompasses various induction pathways, including activation of NMDA, mGlu or P2X receptors. However, the associated specific molecular mechanisms and effects on synaptic physiology are still unclear. We here compare how NMDAR- or P2XR-dependent LTD affect synaptic nanoscale organization and function in rodents. While both LTDs are associated with a loss and reorganization of synaptic AMPARs, only NMDAR-dependent LTD induction triggers a profound reorganization of PSD-95. This modification, which requires the autophagy machinery to remove the T19-phosphorylated form of PSD-95 from synapses, leads to an increase in AMPAR surface mobility. We demonstrate that these post-synaptic changes that occur specifically during NMDAR-dependent LTD result in an increased short-term plasticity improving neuronal responsiveness of depressed synapses. Our results establish that P2XR- and NMDAR-mediated LTD are associated to functionally distinct forms of LTD.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Receptors, N-Methyl-D-Aspartate
/
Long-Term Synaptic Depression
/
Disks Large Homolog 4 Protein
Type of study:
Risk_factors_studies
Limits:
Animals
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2021
Document type:
Article
Affiliation country:
France