Cortical versus thalamic mechanisms underlying spike and wave discharges in GAERS

Genetic absence epilepsy rats from Strasbourg (GAERS) have non-convulsive generalized seizures associated with spike-wave (SW) discharges, which are due to a hyperexcitable state of the thalamo-cortico-thalamic circuits involving the reticular thalamic nucleus (nRt). Investigation of the primary genetically-determined defect responsible for GAERS epilepsy revealed the following abnormalities: (1) increased effectiveness of AMPA receptors dependent glutamate-mediated transmission; (2) impairment of GABA-mediated transmission in the neocortex; (3) increased amplitude of the voltage-dependent low-threshold Ca2+-current (I-T) in the nRt. The maturational profile of these abnormalities supports the conclusion that the abnormality in the I-T current in the nRt is the primary genetically-determined defect, which may secondarily induce the other changes found in the neocortex and thalamus of GAERS.