Priming of group 2 metabotropic glutamate receptors facilitates induction of long-term depression in the dentate gyrus of freely moving rats

Neuropharmacology. 1998 Dec;37(12):1459-64. doi: 10.1016/s0028-3908(98)00150-6.


Activation of group 1 metabotropic glutamate receptors (mGluRs) has been shown to facilitate the induction of tetanically evoked long-term potentiation in vivo, whereas group 2 mGluR antagonists inhibit long-term depression (LTD) in the CA1 region. LTD has not been successfully demonstrated to date in the dentate gyrus of freely moving rats. In this study, it was found that 1-Hz low-frequency stimulation (LFS) when applied via a stimulating electrode chronically implanted in the perforant path, evoked short-term depression (STD) of field excitatory post-synaptic potentials and population spikes measured from the dentate gyrus granule cell layer. Application of the group 2 mGluR agonists (S)-4-carboxyphenylglycine (4C3HPG) or (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV) prior to LFS facilitated the expression of LTD. Application of the group 2 mGluR antagonist (2S)-alpha-ethylglutamic acid (EGLU) prior to agonist application prevented the facilitating effect of the agonists on LFS-induced depression. EGLU did not influence the expression of LFS-induced STD. Neither 4C3HPG, DCG-IV nor EGLU had an effect on basal synaptic transmission at the concentrations used. The present study demonstrates that priming of group 2 mGluRs leads to induction of persistent LTD in the dentate gyrus in vivo, consistent with a role for group 2 mGluRs in metaplasticity.

MeSH terms

  • Animals
  • Benzoates / pharmacology*
  • Cerebral Ventricles / drug effects
  • Cerebral Ventricles / physiology
  • Cyclopropanes / pharmacology*
  • Dentate Gyrus / drug effects
  • Dentate Gyrus / physiology*
  • Electric Stimulation
  • Electroencephalography / drug effects
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology*
  • Glutamates / pharmacology*
  • Glycine / analogs & derivatives*
  • Glycine / pharmacology
  • Male
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Rats
  • Rats, Wistar
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Receptors, Metabotropic Glutamate / physiology*


  • Benzoates
  • Cyclopropanes
  • Excitatory Amino Acid Antagonists
  • Glutamates
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor 2
  • metabotropic glutamate receptor type 1
  • alpha-ethylglutamic acid
  • 2-(2,3-dicarboxycyclopropyl)glycine
  • 4-carboxyphenylglycine
  • Glycine