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Publication : GluN2B-containing NMDA receptors promote wiring of adult-born neurons into olfactory bulb circuits.

First Author  Kelsch W Year  2012
Journal  J Neurosci Volume  32
Issue  36 Pages  12603-11
PubMed ID  22956849 Mgi Jnum  J:187674
Mgi Id  MGI:5437775 Doi  10.1523/JNEUROSCI.1459-12.2012
Citation  Kelsch W, et al. (2012) GluN2B-Containing NMDA Receptors Promote Wiring of Adult-Born Neurons into Olfactory Bulb Circuits. J Neurosci 32(36):12603-11
abstractText  In the developing telencephalon, NMDA receptors (NMDARs) are composed of GluN1 and GluN2B subunits. These "young" NMDARs set a brake on synapse recruitment in neurons of the neonatal cortex. The functional role of GluN2B for synapse maturation of adult-born granule cells (GCs) in the olfactory bulb has not been established and may differ from that of differentiating neurons in immature brain circuits with sparse activity. We genetically targeted GCs by sparse retroviral delivery in mouse subventricular zone that allows functional analysis of single genetically modified cells in an otherwise intact environment. GluN2B-deficient GCs did not exhibit impairment with respect to the first developmental milestones such as synaptogenesis, dendrite formation, and maturation of inhibitory synaptic inputs. However, GluN2B deletion prevented maturation of glutamatergic synaptic input. This severe impairment in synaptic development was associated with a decreased response to novel odors and eventually led to the demise of adult-born GCs. The effect of GluN2B on GC survival is subunit specific, since it cannot be rescued by GluN2A, the subunit dominating mature NMDAR function. Our observations indicate that, GluN2B-containing NMDARs promote synapse activation in adult-born GCs that integrate in circuits with high and correlated synaptic activity. The function of GluN2B-containing NMDARs on synapse maturation can thus be bidirectional depending on the environment.
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