Long-term potentiation in the CA1 hippocampus induced by NR2A subunit-containing NMDA glutamate receptors is mediated by Ras-GRF2/Erk map kinase signaling

PLoS One. 2010 Jul 22;5(7):e11732. doi: 10.1371/journal.pone.0011732.

Abstract

Background: NMDA-type glutamate receptors (NMDARs) are major contributors to long-term potentiation (LTP), a form of synaptic plasticity implicated in the process of learning and memory. These receptors consist of calcium-permeating NR1 and multiple regulatory NR2 subunits. A majority of studies show that both NR2A and NR2B-containing NMDARs can contribute to LTP, but their unique contributions to this form of synaptic plasticity remain poorly understood.

Methodology/principal findings: In this study, we show that NR2A and NR2B-containing receptors promote LTP differently in the CA1 hippocampus of 1-month old mice, with the NR2A receptors functioning through Ras-GRF2 and its downstream effector, Erk Map kinase, and NR2B receptors functioning independently of these signaling molecules.

Conclusions/significance: This study demonstrates that NR2A-, but not NR2B, containing NMDA receptors induce LTP in pyramidal neurons of the CA1 hippocampus from 1 month old mice through Ras-GRF2 and Erk. This difference add new significance to the observation that the relative levels of these NMDAR subtypes is regulated in neurons, such that NR2A-containing receptors become more prominent late in postnatal development, after sensory experience and synaptic activity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CA1 Region, Hippocampal / metabolism*
  • Electrophysiology
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Long-Term Potentiation / genetics
  • Long-Term Potentiation / physiology*
  • Mice
  • Mice, Mutant Strains
  • Models, Biological
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Signal Transduction / genetics
  • Signal Transduction / physiology*
  • ras Guanine Nucleotide Exchange Factors / genetics
  • ras Guanine Nucleotide Exchange Factors / metabolism*

Substances

  • Rasgrf2 protein, mouse
  • Receptors, N-Methyl-D-Aspartate
  • ras Guanine Nucleotide Exchange Factors
  • Extracellular Signal-Regulated MAP Kinases