MHC class i modulates NMDA receptor function and AMPA receptor trafficking

Lawrence Fourgeaud, Christopher M. Davenport, Carolyn M. Tyler, Timothy T. Cheng, Michael B. Spencer, Lisa M. Boulanger

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

Proteins of the major histocompatibility complex class I (MHCI) are known for their role in immunity and have recently been implicated in long-term plasticity of excitatory synaptic transmission. However, the mechanisms by which MHCI influences synaptic plasticity remain unknown. Here we show that endogenous MHCI regulates synaptic responses mediated by NMDA-type glutamate receptors (NMDARs) in the mammalian central nervous system (CNS). The AMPA/NMDA ratio is decreased at MHCI-deficient hippocampa synapses, reflecting an increase in NMDAR-mediated currents. This enhanced NMDAR response is not associated with changes in the levels, subunit composition, or gross subcellular distribution of NMDARs. Increased NMDAR-mediated currents in MHCI-deficient neurons are associated with characteristic changes in AMPA receptor trafficking in response to NMDAR activation. Thus, endogenous MHCI tonically inhibits NMDAR function and controls downstream NMDAR-induced AMPA receptor trafficking during the expression of plasticity.

Original languageEnglish (US)
Pages (from-to)22278-22283
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number51
DOIs
StatePublished - Dec 21 2010

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • GluR
  • Hippocampus
  • Immune

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