Abstracts

The dentate gyrus of the hippocampus controls input of cortical information into the hippocampus proper. This has led to the hypothesis that in temporal lobe epilepsy (TLE) loss of this control may be associated with hippocampal involvement in seizures. Yet, there has been work suggesting that in chronic TLE, the dentate may be less likely to support throughput into the hippocampus. To directly study dentate circuit properties, we used voltage-sensitive dye imaging to assess dentate throughput into CA3 following perforant path stimulation in two conditions: 1) in hippocampal slices from chronically epileptic rats and 2) one week following Pilocarpine-induced status epilepticus destined to produce TLE weeks later. This period following the initial insult is often referred to as the latent period: when seizures are rare but during which time the pathological processes leading to TLE develop. In chronic epilepsy, we found that dentate transfer of synaptic input into CA3 was not significantly increased despite evidence of sprouting (assessed using Timm[rsquo]s stain). In contrast, during the latent period excitation in the dentate was enhanced. Stimulation of the perforant path could produce increased throughput into CA3 leading to burst potentials. This suggests that during the latent period, the dentate may lose its ability to control throughput into the hippocampus proper. The strong inhibitory control of the dentate can powerfully restrain reentrant excitability of the hippocampus. This transient loss of inhibitory control, concurrent with the latent period, suggests that the dentate hyperexcitability may be an important factor in post-SE epileptogenesis. (Supported by NS38572, NS32402 from NINDS, and AES)