Transition to absence seizures and the role of GABAA receptors

Absence seizures appear to be initiated in a putative cortical 'initiation site' by the expression of medium-amplitude 5-9Hz oscillations, which may in part be due to a decreased phasic GABA(A) receptor function. These oscillations rapidly spread to other cortical areas and to the thalamus, leading to fully developed generalized spike and wave discharges. In thalamocortical neurons of genetic models, phasic GABA(A) inhibition is either unchanged or increased, whereas tonic GABA(A) inhibition is increased both in genetic and pharmacological models. This enhanced tonic inhibition is required for absence seizure generation, and in genetic models it results from a malfunction in the astrocytic GABA transporter GAT-1. Contradictory results from inbred and transgenic animals still do not allow us to draw firm conclusions on changes in phasic GABA(A) inhibition in the GABAergic neurons of the nucleus reticularis thalami. Mathematical modelling may enhance our understanding of these competing hypotheses, by permitting investigations of their mechanistic aspects, hence enabling a greater understanding of the processes underlying seizure generation and evolution.