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Updated: Jun 6, 2026

A High-content Assay for Monitoring AMPA Receptor Trafficking
Published on: January 28, 2019
MHC class I modulates NMDA receptor function and AMPA receptor trafficking
Lawrence Fourgeaud1, Christopher M Davenport, Carolyn M Tyler
1Division of Biological Sciences, Section of Neurobiology, University of California at San Diego, La Jolla, CA 92093-0366, USA.
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 hippocampal 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.
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