A critical role for GluN2B-containing NMDA receptors in cortical development and function.
Neuron
; 72(5): 789-805, 2011 Dec 08.
Article
en En
| MEDLINE
| ID: mdl-22153375
ABSTRACT
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 (2Bâ2A). 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 2Bâ2A 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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Corteza Cerebral
/
Receptores de N-Metil-D-Aspartato
/
Regulación del Desarrollo de la Expresión Génica
Límite:
Animals
Idioma:
En
Revista:
Neuron
Asunto de la revista:
NEUROLOGIA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos