GABA Receptors: Are They Missing in Action in Focal Epilepsy Research?

GABA, the key inhibitory neurotransmitter in the adult forebrain, activates pre- and postsynaptic receptors that have been categorized as GABAA, which directly open ligand-gated (or receptor-operated) ion-channels, and GABA, which are metabotropic since they operate through second messengers. Over the last three decades, several studies have addressed the role of GABA receptors in the pathophysiology of generalized and focal epileptic disorders. Here, we will address their involvement in focal epileptic disorders by mainly reviewing in vitro studies that have shown: (i) how either enhancing or decreasing GABA receptor function can favour epileptiform synchronization and thus ictogenesis, although with different features; (ii) the surprising ability of GABA receptor antagonism to disclose ictal-like activity when the excitatory ionotropic transmission is abolished; and (iii) their contribution to controlling seizure-like discharges during repetitive electrical stimuli delivered in limbic structures. In spite of this evidence, the role of GABA receptor function in focal epileptic disorders has been attracting less interest when compared to the numerous studies that have addressed GABA receptor signaling. Therefore, the main aim of our mini-review is to revive interest in the function of GABA receptors in focal epilepsy research.