Targeting the ventral hippocampus for a better model of temporal lobe epilepsy

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PROJECT SUMMARY/ABSTRACT The primary objective of this proposal is to produce a much needed tool for epilepsy research – a model of temporal lobe epilepsy with the strengths of the currently widely used intrahippocampal kainate model but also displaying spontaneous, overtly behavioral seizures, at a high enough frequency to allow scientific investigation. To do this, we propose a simple change to the current induction protocol, with the possibility for a huge impact. Specifically, despite known differences in connectivity and functional properties between dorsal and ventral hippocampus, and the observation that in human patients the anterior hippocampus (corresponding to the ventral hippocampus in rodents) is most likely to show hippocampal sclerosis, in its current form, the intrahippocampal kainate model targets the dorsal (rather than ventral) hippocampus. We hypothesize that better aligning the model to the human condition, by moving the site of initial insult to the ventral hippocampus, will additionally result in a substantially higher frequency of overtly behavioral seizures. This is critically important, as it would provide the field with a much needed tool, allowing investigation of more severe seizures and identification of novel treatment approaches with sufficient statistical power and feasible time frames for data acquisition.