Reduced excitatory drive onto interneurons in the dentate gyrus after status epilepticus

Impaired GABAergic inhibition may contribute to the development of hyperexc itability in epilepsy. We used the pilocarpine model of epilepsy to demonst rate that regulation of excitatory synaptic drive onto GABAergic interneuro ns is impaired during epileptogenesis. Synaptic input from granule cells (G Cs), perforant path, and CA3 inputs onto hilar border interneurons of the d entate gyrus were examined in rat hippocampal slices during the latent peri od (1-8 d) after induction of status epilepticus (SE). Short-term depressio n (STD) of GC inputs to interneurons induced by brief (500-800 msec), repet itive (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 betwe en 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-ev oked granule cell population spikes was lost in SE-experienced rats. Enhanc ed STD was partially mediated by group II metabotropic glutamate receptors, because the selective antagonist, 2S-2-amino-2-(1S,2S-2-carboxycyclopropyl -1yl)-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 I I mGluR agonist, (2S',1R',2R',3R')2-(2,3-dicarboxylcyclopropyl) glycine (1 <mu>M), produced a greater depression of GC input to hilar border interneur ons in SE-experienced rats than in controls. These results indicate that, i n the SE-experienced rat, excitatory drive to hilar border inhibitory inter neurons is weakened through a use-dependent mechanism involving group II me tabotropic glutamate receptors.