Outgrowing seizures in Childhood Absence Epilepsy: time delays and bistability
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We formulate a conductance-based model for a 3-neuron motif associated with Childhood Absence Epilepsy (CAE). The motif consists of neurons from the thalamic relay (TC) and reticular nuclei (RT) and the cortex (CT). We focus on a genetic defect common to the mouse homolog of CAE which is associated with loss of GABAA receptors on the TC neuron, and the fact that myelination of axons as children age can increase the conduction velocity between neurons. We show the combination of low GABAA mediated inhibition of TC neurons and the long corticothalamic loop delay gives rise to a variety of complex dynamics in the motif, including bistability. This bistability disappears as the corticothalamic conduction delay shortens even though GABAA activity remains impaired. Thus the combination of deficient GABAA activity and changing axonal myelination in the corticothalamic loop may be sufficient to account for the clinical course of CAE.
KeywordsChildhood absence epilepsy Time delay
We thank Samuel Berkovic and Peter Camfield for useful comments on the clinical history and inheritance of children with CAE and Anthony Burre for help with the numerical simulations. SAC and YL acknowledge the support of the Natural Sciences and Engineering Research Council of Canada. JM acknowledges support from the William R Kenan, Jr Charitable Trust.
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Conflict of interests
The authors declare that they have no conflict of interest.
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