Abstracts

Rationale: Despite a decade of research, we still have very limited understanding of how seizures are formed. This limits our ability to identify ictal biomarkers and understand how seizures initiate and spread. We present a novel model of in vivo ictogenesis. Methods: Our theoretical and in vitro work suggest that one potential trigger for endogenous seizures is an acute increase in afferent synaptic activity, or "synaptic noise." We recently demonstrated in the intact septo-hippocampal formation that synaptic noise is sufficient to induce hippocampal seizures. Here, we use this strategy in pilocarpine rats to control the timing of seizure onset. Focal microinjections of KCl or bicuculline into a remote brain nucleus triggered hippocampal seizures. Frontal and hippocampal depth electrodes were used on a continuous EEG monitoring system to identify synaptic activity. Results: The model was able to induce temporal lobe seizures in 6 rats. Seizure activity was quantitatively and qualitatively similar to the spontaneous seizures, and occurred within 1 minute of an injection. Conclusions: This model allows direct control of endogenous seizure onset, and differs from other methods of seizure induction (e.g. kindling or chemoconvulsants) because it triggers seizures remotely by overcoming the natural seizure threshold. This method has great potential for future research into seizure mechanisms and biomarkers.