Abstracts

Rationale: The dentate gyrus is predisposed to play the role of a gate, blocking or filtering excitatory activity from the entorhinal cortex (EC) and controlling the amount of excitation that enters the hippocampus. Temporal lobe epilepsy (TLE) is one of the most common seizure disorders and is associated with a characteristic pattern of synaptic reorganization in the hippocampal formation, consisting of neuronal loss and aberrant growth of mossy fiber collaterals into dentate gyrus inner molecular layer. Therefore, a major research focus is to determine how synaptic reorganization will change the gate function of the dentate gyrus during epileptogenesisMethods: Rats were subjected to pilocarpine (PILO) treatment to induce status epilepticus (STEP), which was terminated after 1 hr by diazepam. This induced the subsequent emergence of spontaneous seizures 2-4 weeks post treatment. A voltage sensitive dye imaging technique was used to evaluate dentate gyrus gate function in latent period and chronically epileptic animals by measuring the dynamics of activation of the dentate gyrus in response to stimulation of the perforant path from EC. Patch-clamp techniques were used to examine several aspects of dentate granule cell (DGC) inhibition, including spontaneous and miniature postsynaptic currents (sIPSCs and mIPSCs), as well as tonic GABA-mediated currents due to activation of extrasynaptic GABAA receptors by ambient GABA in latent period (4-14 days post PILO) and chronically epileptic animals (>3 month post PILO). Results: Dentate gyrus gate function collapsed at time points 2-7 days post STEP and recovered to control level by two weeks after STEP and in chronically epileptic animals. Both synaptic and tonic inhibitions were reduced significantly after STEP, temporally concordant with failure of dentate gyrus gate function. STEP-induced dentate gyrus gate failure could be mimicked by application of non-competitive GABAA antagonist picrotoxin (5 M), sufficient to block 30% of inhibitionConclusions: Our results suggest that the dentate gyrus gate function collapse evident 2-7 days after STEP is due to a significant reduction in GABAergic inhibition in dentate granule cells during this period