GABA-A Receptor Function in Typical Absence Seizures

Both human and experimental evidence strongly supports the view of brain region-specific changes in phasic and tonic GABA inhibition in typical absence seizures. In neocortex, a decrease in phasic GABA inhibition characterizes this non-convulsive epileptic phenotype, though more studies are needed to disclose any neuronal type- and layer-specific alterations. The enhanced tonic GABA inhibition, that is present in thalamocortical neurons of genetic and pharmacological models, is both necessary and sufficient for absence seizure generation, and in genetic models it results from a malfunction in the astrocytic GABA transporter GAT-1. Phasic GABA inhibition is either unchanged or increased in thalamocortical neurons of absence models. Contradictory results from inbred and transgenic animals still do not allow us to draw firm conclusions on changes in phasic GABA inhibition in the GABAergic neurons of the nucleus reticularis thalami. Thus, the long-standing view of a widespread GABAergic loss-of-function in typical absence seizures and childhood absence epilepsy is no longer tenable and model systems that use an indiscriminate block of GABA receptors are of no value for understanding the cellular and network mechanisms operating in thalamocortical circuits during typical absence seizures.