| First Author | Wang CC | Year | 2011 |
| Journal | Neuron | Volume | 72 |
| Issue | 5 | Pages | 789-805 |
| PubMed ID | 22153375 | Mgi Jnum | J:178913 |
| Mgi Id | MGI:5300626 | Doi | 10.1016/j.neuron.2011.09.023 |
| Citation | Wang CC, et al. (2011) A Critical Role for GluN2B-Containing NMDA Receptors in Cortical Development and Function. Neuron 72(5):789-805 |
| abstractText | 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. |
