A specific role for group II metabotropic glutamate receptors in hippocampal long-term depression and spatial memory

Neuroscience. 2009 Jan 12;158(1):149-58. doi: 10.1016/j.neuroscience.2008.07.045. Epub 2008 Aug 3.

Abstract

Activity-dependent and sustained alterations in synaptic efficacy are widely regarded as the cellular correlates underlying learning and memory. Metabotropic glutamate receptors (mGluRs) are intrinsically involved in both hippocampal synaptic plasticity and spatial learning. Group II mGluRs are required for persistent hippocampal long-term depression (LTD), but are not required for long-term potentiation (LTP) in the hippocampal CA1 region in vivo. The role of these receptors in spatial learning, and in synaptic plasticity in the dentate gyrus in vivo has not yet been the subject of close scrutiny. We investigated the effects of group II mGluR antagonism on LTP and LTD in the adult rat, at medial perforant path-dentate gyrus synapses, and on spatial learning in the eight-arm radial maze. Daily application of the group 2 mGluR antagonist (2S)-alpha-ethylglutamic acid (EGLU) resulted in impairment of long-term (reference) memory with effects becoming apparent 6 days after training and drug-treatment began. Short-term (working) memory was unaffected throughout the 10-day study. Acute injection of EGLU did not affect either LTD or LTP in the dentate gyrus in vivo. Following six daily applications of EGLU a clear impairment of LTD but not LTP was apparent however. These data support that prolonged antagonism of group II mGluRs results in an impairment of LTD that parallels the appearance of spatial memory deficits arising from group II mGluR antagonism. These findings support the importance of group II mGluRs for spatial memory formation and offer a further link between LTD and the encoding of spatial information in the hippocampus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Excitatory Amino Acid Antagonists / pharmacology
  • Glutamic Acid / metabolism
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology
  • Long-Term Synaptic Depression / drug effects
  • Long-Term Synaptic Depression / physiology*
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Memory / drug effects
  • Memory / physiology*
  • Memory Disorders / chemically induced
  • Memory Disorders / metabolism
  • Memory Disorders / physiopathology
  • Orientation / drug effects
  • Orientation / physiology
  • Rats
  • Rats, Wistar
  • Receptors, Metabotropic Glutamate / drug effects
  • Receptors, Metabotropic Glutamate / metabolism*
  • Space Perception / drug effects
  • Space Perception / physiology*
  • Synapses / drug effects
  • Synapses / metabolism*
  • Synapses / ultrastructure
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology

Substances

  • Excitatory Amino Acid Antagonists
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor 2
  • Glutamic Acid