Status epilepticus results in region-specific alterations in seizure susceptibility along the hippocampal longitudinal axis

Abstract

Temporal lobe epilepsy (TLE) is the most common epilepsy syndrome in adults. In particular, the hippocampus is highly susceptible to abnormal synchronization. Recent advances in the surgical treatment of patients with refractory TLE have shown that multiple hippocampal transections can effectively control seizures. It has been suggested that in TLE the synchrony in the longitudinal connections is required for seizure generation; however the physiological background for the increase in hippocampal synchronization along the longitudinal axis is not fully understood. The hippocampus varies in seizure susceptibility along its longitudinal axis with the ventral hippocampus (VH) region being more seizure-prone and susceptible to neuronal damage than the dorsal hippocampus (DH). In the present study we studied seizure susceptibility along the longitudinal axis of the hippocampus following pilocarpine-induced status epilepticus (SE). In control conditions the VH generates epileptiform activity (EA) more frequently than the DH when exposed to a low Mg(2+)/1Ca(2+)/5K(+) solution. Following SE the probability of inducing epileptiform activity (EA) is similar in the VH and DH slices. This SE-induced change is due to an increase in the proportion of DH slices responding to the low Mg(2+)/1Ca(2+)/5K(+) solution with EA. Moreover, both the VH and DH show similar responses to a low Mg(2+)/1Ca(2+)/5K(+) solution. These findings indicate that the hippocampus undergoes significant functional changes following SE, which may provide the necessary increase of synchrony along the longitudinal axis to generate seizures in TLE.