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NMDAR-dependent long-term depression is associated with increased short term plasticity through autophagy mediated loss of PSD-95.
- Source :
-
Nature communications [Nat Commun] 2021 May 14; Vol. 12 (1), pp. 2849. Date of Electronic Publication: 2021 May 14. - Publication Year :
- 2021
-
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.
- Subjects :
- Adenosine Triphosphate administration & dosage
Animals
Autophagy physiology
Cells, Cultured
Disks Large Homolog 4 Protein deficiency
Female
Hippocampus cytology
Hippocampus physiology
In Vitro Techniques
Male
Mice
Mice, Inbred C57BL
Miniature Postsynaptic Potentials physiology
Models, Neurological
N-Methylaspartate administration & dosage
Neuronal Plasticity physiology
Neurons cytology
Neurons drug effects
Neurons physiology
Rats
Rats, Sprague-Dawley
Receptors, AMPA physiology
Receptors, Purinergic P2X physiology
Disks Large Homolog 4 Protein physiology
Long-Term Synaptic Depression physiology
Receptors, N-Methyl-D-Aspartate physiology
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 12
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 33990590
- Full Text :
- https://doi.org/10.1038/s41467-021-23133-9