Ictogenesis proceeds through discrete phases in hippocampal CA1 seizures in mice

John-Sebastian Mueller, Fabio C. Tescarollo, Trong Huynh, Daniel A. Brenner, Daniel J. Valdivia, Kanyin Olagbegi, Sahana Sangappa, Spencer C. Chen and Hai Sun ()
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John-Sebastian Mueller: Rutgers Robert Wood Johnson Medical School
Fabio C. Tescarollo: Rutgers Robert Wood Johnson Medical School
Trong Huynh: Rutgers Robert Wood Johnson Medical School
Daniel A. Brenner: Rutgers Robert Wood Johnson Medical School
Daniel J. Valdivia: Rutgers Robert Wood Johnson Medical School
Kanyin Olagbegi: Rutgers Robert Wood Johnson Medical School
Sahana Sangappa: Rutgers Robert Wood Johnson Medical School
Spencer C. Chen: Rutgers Robert Wood Johnson Medical School
Hai Sun: Rutgers Robert Wood Johnson Medical School

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: 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 of ictogenesis, 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 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 stepwise process 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. The pulsogram was then constructed in seizures recorded from a murine model of temporal lobe epilepsy and it depicted a similar reverberance preceding spontaneous seizures. The discovery of these distinct phases of ictogenesis may offer means to abort a seizure before it develops.

Date: 2023
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DOI: 10.1038/s41467-023-41711-x

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