Ictogenesis Proceeds Through Discrete Phases in Hippocampal CA1 Seizures

Abstract

Epilepsy is characterized by spontaneous non-provoked seizures, yet the mechanisms that trigger a seizure and allow its evolution remain underexplored. To dissect out phases implicated in the development of a seizure, we evoked hypersynchronous activity with optogenetic stimulation. Focal optogenetic activation of putative excitatory neurons in the mouse hippocampal CA1 reliably evoked convulsive seizures in awake mice. A novel time-vs-time “pulsogram” plot characterized the evolution of the EEG pulse response from a light evoked response to induced seizure activity. Our results depict ictogenesis as a stepwiseprocess comprised of three distinctive phases demarcated by two transition points. The induction phase undergoes the first transition to reverberant phase activity, followed by the second transition into the paroxysmal phase or a seizure. Non-seizure responses are confined to either induction or reverberant phases, suggesting ictogenesis can be stopped at these stages, thus offering novel therapeutic perspectives to abort a seizure before it develops.