Inhibition, oscillations and focal seizures: An overview inspired by some historical notes

GABA (i.e., γ-amino-butyric acid) is the main inhibitory neurotransmitter in the adult mammalian brain. Once released from inhibitory cells, it activates pre- and post-synaptic GABA receptors that have been categorized into type A and type B. GABA_A receptors open ionotropic anionic channels while GABA_B receptors are metabotropic, acting through second messengers. In the 1980s, decreased GABA receptor signaling was considered an appealing factor in making cortical neurons generate synchronous epileptiform oscillations and thus a good, perhaps obvious, candidate for causing focal epileptic disorders. However, studies published during the last four decades have demonstrated that interneuron firing - which causes GABA release and thus GABA_A receptor activation - can lead to the generation of both physiological (e.g., theta and gamma oscillations or sharp wave-ripples) and pathological oscillations including focal interictal spikes, high frequency oscillations and seizures. Taken together, the reviews published in this special issue of Neurobiology of Disease highlight the key role of inhibition, and in particular of GABA_A receptor signaling, in neuronal network functions under physiological and pathological conditions that include epilepsy and Alzheimer's disease.