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Convulsive seizures from experimental focal cortical dysplasia occur independently of cell misplacement

Author

Listed:
  • Lawrence S. Hsieh

    (and Cellular and Molecular Physiology, Yale University School of Medicine)

  • John H. Wen

    (and Cellular and Molecular Physiology, Yale University School of Medicine)

  • Kumiko Claycomb

    (Yale University School of Medicine)

  • Yuegao Huang

    (Magnetic Resonance Research Center, Yale University School of Medicine)

  • Felicia A. Harrsch

    (Wesleyan University)

  • Janice R. Naegele

    (Wesleyan University)

  • Fahmeed Hyder

    (Magnetic Resonance Research Center, Yale University School of Medicine)

  • Gordon F. Buchanan

    (Yale University School of Medicine)

  • Angelique Bordey

    (and Cellular and Molecular Physiology, Yale University School of Medicine)

Abstract

Focal cortical dysplasia (FCD), a local malformation of cortical development, is the most common cause of pharmacoresistant epilepsy associated with life-long neurocognitive impairments. It remains unclear whether neuronal misplacement is required for seizure activity. Here we show that dyslamination and white matter heterotopia are not necessary for seizure generation in a murine model of type II FCDs. These experimental FCDs generated by increasing mTOR activity in layer 2/3 neurons of the medial prefrontal cortex are associated with tonic-clonic seizures and a normal survival rate. Preventing all FCD-related defects, including neuronal misplacement and dysmorphogenesis, with rapamycin treatments from birth eliminates seizures, but seizures recur after rapamycin withdrawal. In addition, bypassing neuronal misplacement and heterotopia using inducible vectors do not prevent seizure occurrence. Collectively, data obtained using our new experimental FCD-associated epilepsy suggest that life-long treatment to reduce neuronal dysmorphogenesis is required to suppress seizures in individuals with FCD.

Suggested Citation

  • Lawrence S. Hsieh & John H. Wen & Kumiko Claycomb & Yuegao Huang & Felicia A. Harrsch & Janice R. Naegele & Fahmeed Hyder & Gordon F. Buchanan & Angelique Bordey, 2016. "Convulsive seizures from experimental focal cortical dysplasia occur independently of cell misplacement," Nature Communications, Nature, vol. 7(1), pages 1-12, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11753
    DOI: 10.1038/ncomms11753
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