Activation of extrasynaptic NMDA receptors induces LTD in rat hippocampal CA1 neurons

Brain Res Bull. 2013 Apr:93:10-6. doi: 10.1016/j.brainresbull.2012.12.003. Epub 2012 Dec 25.

Abstract

In the adult rat hippocampus, activation of N-methyl-d-aspartate receptors (NMDARs) is required for the induction of certain forms of synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD). Several studies have indicated the opposing role of synaptic NMDARS (S-NMDARs) versus extrasynaptic NMDARs (ES-NMDARs) in CREB-dependent gene regulation and neuronal survival/death. The contribution of ES-NMDARs in synaptic plasticity, however, remains unclear. Here we investigated the contribution of ES-NMDARs on LTD induction in CA1 neurons of rat hippocampal slices. ES-NMDARs were selectively activated by theta burst stimulation (TBS) after selective blockade of S-NMDARs with pairing of 5 Hz stimulation and MK-801, an irreversible use-dependent antagonist of NMDARs. Application of TBS in naïve slices evoked a transient potentiation. In contrast, the activation of ES-NMDARs evoked a robust LTD. These results suggest the involvement of ES-NMDARs in LTD induction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Biophysics
  • CA1 Region, Hippocampal / cytology*
  • Dizocilpine Maleate / pharmacology
  • Electric Stimulation
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • GABA Antagonists / pharmacology
  • In Vitro Techniques
  • Long-Term Synaptic Depression / drug effects
  • Long-Term Synaptic Depression / physiology*
  • Male
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Picrotoxin / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Synapses / drug effects
  • Synapses / physiology*

Substances

  • Excitatory Amino Acid Antagonists
  • GABA Antagonists
  • Receptors, N-Methyl-D-Aspartate
  • Picrotoxin
  • Dizocilpine Maleate