Synapse-specific regulation of AMPA receptor function by PSD-95

Jean Claude Béïque, Da Ting Lin, Myoung Goo Kang, Hiro Aizawa, Kogo Takamiya, Richard L. Huganir

Research output: Contribution to journalArticle

Abstract

PSD-95 is a major protein found in virtually all mature excitatory glutamatergic synapses in the brain. Here, we have addressed the role of PSD-95 in controlling glutamatergic synapse function by generating and characterizing a PSD-95 KO mouse. We found that the α-amino-3-hydroxy-5-methylisoxazole-4- propionic acid (AMPA) subtype of glutamate receptor (AMPAR)-mediated synaptic transmission was reduced in these mice. Two-photon (2P) uncaging of MNI-glutamate onto individual spines suggested that the decrease in AMPAR function in the PSD-95 KO mouse stems from an increase in the proportion of "silent" synapses i.e., synapses containing N-methyl-D-aspartate (NMDA) receptors (NMDARs) but no AMPARs. Unexpectedly, the silent synapses in the KO mouse were located onto morphologically mature spines. We also observed that a significant population of synapses appeared unaffected by PSD-95 gene deletion, suggesting that the functional role of PSD-95 displays synapse-specificity. In addition, we report that the decay of NMDAR-mediated current was slower in KO mice: The contribution of NR2B subunit containing receptors to the NMDAR-mediated synaptic current was greater in KO mice. The greater occurrence of silent synapses might be related to the greater magnitude of potentiation after long-term potentiation induction observed in these mice. Together, these results suggest a synapse-specific role for PSD-95 in controlling synaptic function that is independent of spine morphology.

Original languageEnglish (US)
Pages (from-to)19535-19540
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number51
DOIs
StatePublished - Dec 19 2006

Keywords

  • Glutamate receptors
  • Hippocampus
  • Spines
  • Synaptic transmission
  • Two-photon uncaging

ASJC Scopus subject areas

  • General

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