Journal article
mGluR5 and NMDA Receptors Drive the Experience- and Activity-Dependent NMDA Receptor NR2B to NR2A Subunit Switch
Neuron (Cambridge, Mass.), v 70(2), pp 339-351
28 Apr 2011
PMID: 21521618
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
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Details
- Title
- mGluR5 and NMDA Receptors Drive the Experience- and Activity-Dependent NMDA Receptor NR2B to NR2A Subunit Switch
- Creators
- Jose A. Matta - National Institutes of HealthMichael C. Ashby - Natl Inst Neurol Disorders & Stroke, Dev Synapt Plast Sect, NIH, Bethesda, MD 20892 USAAntonio Sanz-Clemente - National Institutes of HealthKatherine W. Roche - National Institutes of HealthJohn T. R. Isaac - Natl Inst Neurol Disorders & Stroke, Dev Synapt Plast Sect, NIH, Bethesda, MD 20892 USA
- Publication Details
- Neuron (Cambridge, Mass.), v 70(2), pp 339-351
- Publisher
- Elsevier
- Number of pages
- 13
- Grant note
- ZIANS002994 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) NIGMS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) National Institute of Neurological Disorders and Stroke; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000291073700014
- Scopus ID
- 2-s2.0-79955094725
- Other Identifier
- 991020099054304721
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- Web of Science research areas
- Neurosciences