GABA_B 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_B, which are metabotropic since they operate through second messengers. Over the last three decades, several studies have addressed the role of GABA_B 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_B receptor function can favour epileptiform synchronization and thus ictogenesis, although with different features; (ii) the surprising ability of GABA_B 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_B receptor function in focal epileptic disorders has been attracting less interest when compared to the numerous studies that have addressed GABA_A receptor signaling. Therefore, the main aim of our mini-review is to revive interest in the function of GABA_B receptors in focal epilepsy research.