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Publication : Downregulation of NR3A-containing NMDARs is required for synapse maturation and memory consolidation.

First Author  Roberts AC Year  2009
Journal  Neuron Volume  63
Issue  3 Pages  342-56
PubMed ID  19679074 Mgi Jnum  J:154942
Mgi Id  MGI:4411960 Doi  10.1016/j.neuron.2009.06.016
Citation  Roberts AC, et al. (2009) Downregulation of NR3A-containing NMDARs is required for synapse maturation and memory consolidation. Neuron 63(3):342-56
abstractText  NR3A is the only NMDA receptor (NMDAR) subunit that downregulates sharply prior to the onset of sensitive periods for plasticity, yet the functional importance of this transient expression remains unknown. To investigate whether removal/replacement of juvenile NR3A-containing NMDARs is involved in experience-driven synapse maturation, we used a reversible transgenic system that prolonged NR3A expression in the forebrain. We found that removal of NR3A is required to develop strong NMDAR currents, full expression of long-term synaptic plasticity, a mature synaptic organization characterized by more synapses and larger postsynaptic densities, and the ability to form long-term memories. Deficits associated with prolonged NR3A were reversible, as late-onset suppression of transgene expression rescued both synaptic and memory impairments. Our results suggest that NR3A behaves as a molecular brake to prevent the premature strengthening and stabilization of excitatory synapses and that NR3A removal might thereby initiate critical stages of synapse maturation during early postnatal neural development.
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