Activation of metabotropic glutamate receptor type 2/3 suppresses transmission at rat hippocampal mossy fibre synapses

J Physiol. 1996 Jun 1;493 ( Pt 2)(Pt 2):447-55. doi: 10.1113/jphysiol.1996.sp021395.

Abstract

1. The effects of metabotropic glutamate receptor (mGluR) agonists on excitatory transmission at mossy fibre-CA3 synapses were studied in rat hippocampal slice preparations using both extracellular and whole-cell clamp recording techniques. 2. Application of a novel and potent mGluR2/mGluR3-specific agonist (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV, 0.1 microM) reversibly suppressed field excitatory postsynaptic potentials evoked by mossy fibre stimulation. DCG-IV at the same concentration did not affect other glutamatergic excitatory transmissions at the commissural/associational input to CA3 or at the Schaffer collateral/commissural input to CA1 regions. 3. This suppressing effect of DCG-IV on mossy fibre transmission was dose dependent and partly antagonized by a competitive mGluR antagonist (+)-methyl-4-carboxylphenylglycine (1 mM). 4. The field potential changes induced by pressure application of glutamate (0.1 mM) to the stratum lucidum of the CA3 region was unaffected by 0.1 microM DCG-IV. 5. In whole-cell clamp experiments, 0.1 microM DCG-IV suppressed excitatory postsynaptic currents evoked by mossy fibre stimulation without inducing detectable inward current in CA3 neurons, and paired-pulse facilitation was enhanced by DCG-IV application. 6. These results suggest that mGluR2/mGluR3 are specifically expressed at mossy fibre synapses in the hippocampal CA3 region, and activation of the receptor suppresses synaptic transmission by an action on a presynaptic site.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclopropanes / pharmacology*
  • Depression, Chemical
  • Electric Stimulation
  • Electrophysiology
  • Extracellular Space / drug effects
  • Extracellular Space / physiology
  • Glycine / analogs & derivatives*
  • Glycine / pharmacology
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / physiology*
  • In Vitro Techniques
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Nerve Fibers / drug effects
  • Nerve Fibers / physiology*
  • Patch-Clamp Techniques
  • Rats
  • Rats, Wistar
  • Receptors, Metabotropic Glutamate / agonists
  • Receptors, Metabotropic Glutamate / metabolism*
  • Synapses / drug effects
  • Synapses / physiology*
  • Synaptic Transmission / drug effects*

Substances

  • Cyclopropanes
  • Receptors, Metabotropic Glutamate
  • 2-(2,3-dicarboxycyclopropyl)glycine
  • Glycine