MGluR5 and NMDA Receptors Drive the Experience- and Activity-Dependent NMDA Receptor NR2B to NR2A Subunit Switch

Jose A. Matta*, Michael C. Ashby, Antonio Sanz-Clemente, Katherine W. Roche, John T R Isaac

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

Abstract

In cerebral cortex there is a developmental switch from NR2B- to NR2A-containing NMDA receptors (NMDARs) driven by activity and sensory experience. This subunit switch alters NMDAR function, influences synaptic plasticity, and its dysregulation is associated with neurological disorders. However, the mechanisms driving the subunit switch are not known. Here, we show in hippocampal CA1 pyramidal neurons that the NR2B to NR2A switch driven acutely by activity requires activation of NMDARs and mGluR5, involves PLC, Ca2+ release from IP3R-dependent stores, and PKC activity. In mGluR5 knockout mice the developmental NR2B-NR2A switch in CA1 is deficient. Moreover, in visual cortex of mGluR5 knockout mice, the NR2B-NR2A switch evoked in vivo by visual experience is absent. Thus, we establish that mGluR5 and NMDARs are required for the activity-dependent NR2B-NR2A switch and play a critical role in experience-dependent regulation of NMDAR subunit composition in vivo.

Original languageEnglish (US)
Pages (from-to)339-351
Number of pages13
JournalNeuron
Volume70
Issue number2
DOIs
StatePublished - Apr 28 2011

ASJC Scopus subject areas

  • Neuroscience(all)

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