Activation of NMDA receptors reverses desensitization of mGluR5 in native and recombinant systems

S. Alagarsamy, M. J. Marino, S. T. Rouse, R. W. Gereau IV, S. F. Heinemann, P. J. Conn

Research output: Contribution to journalArticle

181 Scopus citations

Abstract

The metabotropic glutamate receptor, mGluR5, has a critical role in induction of NMDA-receptor-dependent forms of synaptic plasticity and excitotoxicity. This is likely mediated by a reciprocal positive-feedback interaction between these two glutamate receptor subtypes in which activation of mGluR5 potentiates NMDA receptor currents and NMDA receptor activation potentiates mGluR5-mediated responses. We have investigated the mechanism by which NMDA receptor activation modulates mGluR5 function and find evidence that this response is mediated by activation of a protein phosphatase and a resultant dephosphorylation of protein kinase C phosphorylation sites on mGluR5. This form of neuromodulation may be important in a number of normal and pathological processes that involve activation of the NMDA receptor.

Original languageEnglish
Pages (from-to)234-240
Number of pages7
JournalNature neuroscience
Volume2
Issue number3
DOIs
StatePublished - Mar 1 1999
Externally publishedYes

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