PubMed 22153375

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kir6.2

Title: A critical role for GluN2B-containing NMDA receptors in cortical development and function.

Authors: Chih-Chieh Wang, Richard G Held, Shiao-Chi Chang, Lingling Yang, Eric Delpire, Anirvan Ghosh, Benjamin J Hall

Journal, date & volume: Neuron, 2011 Dec 8 , 72, 789-805

PubMed link:

The subunit composition of N-methyl D-aspartate receptors (NMDARs) is tightly regulated during cortical development. NMDARs are initially dominated by GluN2B (NR2B), whereas GluN2A (NR2A) incorporation increases after birth. The function of GluN2B-containing NMDARs during development, however, is incompletely understood. We generated a mouse in which we genetically replaced GluN2B with GluN2A (2B→2A). Although this manipulation restored NMDAR-mediated currents at glutamatergic synapses, it did not rescue GluN2B loss of function. Protein translation-dependent homeostatic synaptic plasticity is occluded in the absence of GluN2B, and AMPA receptor contribution is enriched at excitatory cortical synapses. Our experiments indicate that specificity of GluN2B-mediated signaling is due to its unique interaction with the protein effector alpha calcium-calmodulin kinase II and the regulation of the mTOR pathway. Homozygous 2B→2A mice exhibited high rates of lethality, suppressed feeding, and depressed social exploratory behavior. These experiments indicate that GluN2B-containing NMDARs activate unique cellular processes that cannot be rescued by replacement with GluN2A.