NMDA receptor subunit composition controls synaptic plasticity by regulating binding to CaMKII

Barria, A., Malinow, R. (October 2005) NMDA receptor subunit composition controls synaptic plasticity by regulating binding to CaMKII. Neuron, 48 (2). pp. 289-301. ISSN 0896-6273 (Print)

URL: https://www.ncbi.nlm.nih.gov/pubmed/16242409
DOI: 10.1016/j.neuron.2005.08.034


Calcium entry through postsynaptic NMDA-Rs and subsequent activation of CaMKII trigger synaptic plasticity in many brain regions. Active CaMKII can bind to NMDA-Rs, but the physiological role of this interaction is not well understood. Here, we test if association between active CaMKII and synaptic NMDA-Rs is required for synaptic plasticity. Switching synaptic NR2B-containing NMDA-Rs that bind CaMKII with high affinity with those containing NR2A, a subunit with low affinity for CaMKII, dramatically reduces LTP. Expression of NR2A with mutations that increase association to active CaMKII recovers LTP. Finally, driving into synapses NR2B with mutations that reduce association to active CaMKII prevents LTP. Spontaneous activity-driven potentiation shows similar results. We conclude that association between active CaMKII and NR2B is required for different forms of synaptic enhancement. The switch from NR2B to NR2A content in synaptic NMDA-Rs normally observed in many brain regions may contribute to reduced plasticity by controlling the binding of active CaMKII.

Item Type: Paper
Uncontrolled Keywords: Animals Animals Newborn Benzylamines pharmacology Ca(2+)-Calmodulin Dependent Protein Kinase metabolism Cell Line Comparative Study Cricetinae Electric Stimulation methods Excitatory Amino Acid Antagonistsp harmacology Excitatory Postsynaptic Potentials drug effects Gene Expression genetics Green Fluorescent Proteins metabolism Hippocampus cytology In Vitro Magnesium pharmacology Membrane Potentials drug effects physiology Mutagenesis physiology Neuronal Plasticity physiology Neurons cytology drug effects Patch-Clamp Techniques methods Piperidines pharmacology Protein Binding physiology Protein Kinase Inhibitors pharmacology Rats Rats Sprague-Dawley Receptors, N-Methyl-D-Aspartate physiology Sulfonamides pharmacology Synapses physiology Time Factors Transfection methods
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > NMDA receptor
CSHL Authors:
Communities: CSHL labs > Malinow lab
Depositing User: CSHL Librarian
Date: 20 October 2005
Date Deposited: 17 Jan 2012 16:14
Last Modified: 02 May 2018 16:10
Related URLs:
URI: https://repository.cshl.edu/id/eprint/22533

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