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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Roberts, AC; Díez-García, J; Rodriguiz, RM; López, IP; Luján, R; Martínez-Turrillas, R; Picó, E; Henson, MA; Bernardo, DR; Jarrett, TM; Clendeninn, DJ; López-Mascaraque, L; Feng, G; Lo, DC; Wesseling, JF; Wetsel, WC; Philpot, BD; Pérez-Otaño, I

Published Date

  • August 13, 2009

Published In

Volume / Issue

  • 63 / 3

Start / End Page

  • 342 - 356

PubMed ID

  • 19679074

Electronic International Standard Serial Number (EISSN)

  • 1097-4199

Digital Object Identifier (DOI)

  • 10.1016/j.neuron.2009.06.016

Language

  • eng

Conference Location

  • United States