Outgrowing seizures in Childhood Absence Epilepsy: time delays and bistability

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 GABA_A 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 GABA_A 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 GABA_A activity remains impaired. Thus the combination of deficient GABA_A activity and changing axonal myelination in the corticothalamic loop may be sufficient to account for the clinical course of CAE.