UC San Diego

Mesial temporal lobe epilepsy is a common focal seizure disorder in adults. Unfortunately, the onset of spontaneous and chronic seizures is the only current method of diagnosis. However, previous research has demonstrated that mTLE originates in the hippocampus by altering neuron concentrations and synaptic connections through a process called epileptogenesis. These alterations occur in the dentate gyrus of the hippocampus – a subregion that is also critical for pattern separation memory. As shown by previous rat and human studies, pattern separation allows the brain to differentiate very similar experiences from each other. Therefore, this study hypothesized that rats induced with mTLE would display impairments on a dentate-dependent task prior to the onset of spontaneous, recurrent seizures. This was tested by administering kainic acid to 40 day postnatal rats to cause status epilepticus, then training them using the adjacent arms of an 8-Radial Arm Maze. The kainate-induced rats were also monitored 24-hours, in order to distinguish between asymptomatic and chronically epileptic rats. After behavioral testing, the hippocampal tissue of control and kainate-induced rats were immunostained for hilar somatostatin interneurons and stained with Timm sulphide silver to visualize mossy fiber sprouting – two hallmark dentate alterations of epileptogenesis. We found a significant impairment in dentate-dependent behavior among the all kainate-induced rats (asymptomatic + chronically epileptic). However, a significant impairment was not found in the asymptomatic, kainate-induced rats alone, due to the age-dependent effects of kainate induction on behavior. Additionally, increased mossy fiber sprouting correlated with less hilar somatostatin interneurons of the dorsal dentate gyrus.