The mechanism of presynaptic long-term depression mediated by group I metabotropic glutamate receptors

Cell Mol Neurobiol. 2003 Apr;23(2):187-203. doi: 10.1023/a:1022949922364.

Abstract

1. Metabotropic glutamate receptors (mGluRs) are known to play a role in synaptic plasticity. In a study of rat hippocampal brain slices, we find that a brief perfusion of a group I mGluR agonist, (S)-3,5-dihydroxyphenylglycine (DHPG), induced a robust long-term depression (DHPG-LTD) in area CA1. 2. The action was accompanied by an enhancement of the paired-pulse facilitation (PPF) ratio. 3. At the same time DHPG enhanced ionophoretic responses to alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA), kainic acid (KA), and N-methyl-D-aspartate (NMDA) in CA1 pyramidal neurons. This was only partially reversed by washing. 4. These observations indicate that DHPG exerts two opposing actions, suppression of the synaptic transmission and facilitation of postsynaptic responses. However, the presynaptic action dominates, since the net effect of monosynaptic activation is a reduction of response. 5. Perfusion of DHPG reduced three calcium-dependent responses in CA3 pyramidal neurons, which are presynaptic to CA1 neurons. These are calcium spike width and amplitude, after-hyperpolarization (AHP), and spike frequency adaptation (SFA). 6. These results suggest that the DHPG-LTD results from modulation of the presynaptic calcium currents by group I mGluRs.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology*
  • Hippocampus / drug effects
  • Hippocampus / physiology
  • Long-Term Synaptic Depression / drug effects
  • Long-Term Synaptic Depression / physiology*
  • Male
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / physiology*
  • Rats
  • Rats, Wistar
  • Receptors, Metabotropic Glutamate / agonists
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Receptors, Metabotropic Glutamate / physiology*

Substances

  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor type 1