Elevated PSD-95 Blocks Ion-flux Independent LTD: A Potential New Role for PSD-95 in Synaptic Plasticity

Neuroscience. 2021 Feb 21:456:43-49. doi: 10.1016/j.neuroscience.2020.02.020. Epub 2020 Feb 28.

Abstract

We recently demonstrated that NMDA receptors (NMDARs) are capable of ion-flux independent signaling through conformational change in the NMDAR intracellular domain resulting in long-term depression of synaptic transmission (LTD). Here we show that PSD-95 overexpression blocks agonist induced conformational movement in the NMDAR intracellular domain as well as LTD that is NMDAR-dependent and ion-flux independent. Interestingly, previous studies indicate that overexpressed PSD-95 does not block NMDAR-dependent LTD. These data support a model where ion-flux independent LTD is predominant in young animals, which have synapses with low amounts of PSD-95, whereas only ion flux dependent LTD occurs at more mature synapses, which have more PSD-95 that would block ion-flux independent LTD. These results may reconcile different findings regarding ion-flux independent LTD.

Keywords: MAGUK; NMDA receptor; conformational movement; long-term depression; metabotropic signaling; post-synaptic density protein 95.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Disks Large Homolog 4 Protein
  • Hippocampus* / metabolism
  • Long-Term Synaptic Depression
  • Neuronal Plasticity*
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Synapses / metabolism
  • Synaptic Transmission

Substances

  • Disks Large Homolog 4 Protein
  • Receptors, N-Methyl-D-Aspartate