Reduced Excitatory Drive Onto Interneurons in the Dentate Gyrus After Status Epilepticus

J Neurosci. 2001 Mar 15;21(6):2048-57. doi: 10.1523/JNEUROSCI.21-06-02048.2001.

Abstract

Impaired GABAergic inhibition may contribute to the development of hyperexcitability in epilepsy. We used the pilocarpine model of epilepsy to demonstrate that regulation of excitatory synaptic drive onto GABAergic interneurons is impaired during epileptogenesis. Synaptic input from granule cells (GCs), perforant path, and CA3 inputs onto hilar border interneurons of the dentate gyrus were examined in rat hippocampal slices during the latent period (1-8 d) after induction of status epilepticus (SE). Short-term depression (STD) of GC inputs to interneurons induced by brief (500-800 msec), repetitive (5-20 Hz) stimulation, as well as paired-pulse depression at both GC and CA3 inputs to interneurons, were significantly (p < 0.05) enhanced in SE-experienced rats. In contrast, we found no significant differences between SE-experienced and age-matched control rats in the properties of minimal EPSCs evoked at low frequency (0.3 Hz). Consistent with reduced GABAergic inhibition onto granule cells, paired-pulse depression of perforant path-evoked granule cell population spikes was lost in SE-experienced rats. Enhanced STD was partially mediated by group II metabotropic glutamate receptors, because the selective antagonist, 2S-2-amino-2-(1S,2S-2-carboxycyclopropyl-1-yl)-3-(xanth-9-yl)propanoic acid, attenuated STD in SE-experienced rats but had no effect on STD of GC inputs in the normal adult rat. The group II mGluR agonist, (2S',1R',2R',3R')-2-(2,3-dicarboxylcyclopropyl) glycine (1 micrometer), produced a greater depression of GC input to hilar border interneurons in SE-experienced rats than in controls. These results indicate that, in the SE-experienced rat, excitatory drive to hilar border inhibitory interneurons is weakened through a use-dependent mechanism involving group II metabotropic glutamate receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Animals
  • Dentate Gyrus / pathology
  • Dentate Gyrus / physiopathology*
  • Disease Models, Animal
  • Electric Stimulation
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials
  • In Vitro Techniques
  • Interneurons / metabolism*
  • Interneurons / pathology
  • Male
  • Neural Inhibition
  • Neuronal Plasticity
  • Patch-Clamp Techniques
  • Pilocarpine
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Receptors, Metabotropic Glutamate / metabolism
  • Status Epilepticus / chemically induced
  • Status Epilepticus / pathology
  • Status Epilepticus / physiopathology*
  • Synaptic Transmission

Substances

  • Excitatory Amino Acid Antagonists
  • Receptors, Metabotropic Glutamate
  • Pilocarpine