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.
Every year in the US, there are 150,000 new cases of epilepsy diagnosed and up to 50,000 deaths associated with seizures. Better treatment options require a greater understanding of the disorder, which is currently hampered by the need for better tools to study large seizures. This proposal provides a rodent model of temporal lobe epilepsy which better mimics the human condition and displays a sufficiently high frequency of behavioral seizures to allow meaningful investigation, improved understanding of the disorder, and identification of novel intervention strategies.
| Zeidler, Zachary; Brandt-Fontaine, Mikaela; Leintz, Caara et al. (2018) Targeting the Mouse Ventral Hippocampus in the Intrahippocampal Kainic Acid Model of Temporal Lobe Epilepsy. eNeuro 5: |
| Christenson Wick, Zoé; Krook-Magnuson, Esther (2018) Specificity, Versatility, and Continual Development: The Power of Optogenetics for Epilepsy Research. Front Cell Neurosci 12:151 |
| Zeidler, Zachary; Krook-Magnuson, Esther (2016) One Site to Rule Them All: Toward a Master Regulator of Ictal Activity. Epilepsy Curr 16:170-1 |
