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Ictogenesis proceeds through discrete phases in hippocampal CA1 seizures in mice

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Listed:
  • 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
    Rutgers New Jersey 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)

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.

Suggested Citation

  • John-Sebastian Mueller & Fabio C. Tescarollo & Trong Huynh & Daniel A. Brenner & Daniel J. Valdivia & Kanyin Olagbegi & Sahana Sangappa & Spencer C. Chen & Hai Sun, 2023. "Ictogenesis proceeds through discrete phases in hippocampal CA1 seizures in mice," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41711-x
    DOI: 10.1038/s41467-023-41711-x
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