Abstract
The main neurotransmitter in the brain responsible for the inhibition of neuronal activity is γ-aminobutyric acid (GABA). It plays a crucial role in circuit formation during development, both via its primary effects as a neurotransmitter and also as a trophic factor. The GABA(B) receptors (GABA(B)Rs) are G protein-coupled metabotropic receptors; on one hand, they can influence proliferation and migration; and, on the other, they can inhibit cells by modulating the function of K(+) and Ca(2+) channels, doing so on a slower time scale and with a longer-lasting effect compared to ionotropic GABA(A) receptors. GABA(B)Rs are expressed pre- and post-synaptically, at both glutamatergic and GABAergic terminals, thus being able to shape neuronal activity, plasticity, and the balance between excitatory and inhibitory synaptic transmission in response to varying levels of extracellular GABA concentration. Furthermore, given their subunit composition and their ability to form complexes with several associated proteins, GABA(B)Rs display heterogeneity with regard to their function, which makes them a promising target for pharmacological interventions. This review will describe (i) the latest results concerning GABA(B)Rs/GABA(B)R-complex structures, their function, and the developmental time course of their appearance and functional integration in the brain, (ii) their involvement in manifestation of various pathophysiological conditions, and (iii) the current status of preclinical and clinical studies involving GABA(B)R-targeting drugs.