Pathophysiological role of extrasynaptic GABA A receptors in typical absence epilepsy

GABA is the principal inhibitory neurotransmitter in the mammalian CNS. It acts via two classes of receptors, the GABA A, a ligand gated ion channel (ionotropic receptor) and the metabotropic G-protein coupled GABA B receptor. While synaptic GABA A receptors underlie classical 'phasic' GABA A receptor-mediated inhibition, extrasynaptic GABA A receptors (eGABA AR) mediate a new form of inhibition, termed 'tonic' GABA A inhibition. The subunit composition of eGABA ARs differs from those present at the synapse, resulting in pharmacologically and functionally distinct properties. In this mini-review the findings presented at the 2 nd Neuroscience Day meeting held last July in Malta will be summarized. Particular emphasis will be given to the important pathophysiological role of eGABA AR within thalamocortical circuits as a major player in nonconvulsive absence epilepsy. The new findings presented at the conference suggest that enhanced tonic inhibition is a common cause of seizures in several animal models of absence epilepsy and may provide new targets for therapeutic intervention.