The neurobiology of GABA receptors

Gamma-aminobutyric acid (GABA) was first identified in 1950 (Roberts 1950; Awapara 1950) in brain extracts of various animal species and was subsequently found to be the principal inhibitory neurotransmitter in the central nervous system (CNS). GABA is synthesized as a result of decarboxylation of glutamic acid and is released by neurons into the synaptic cleft in order to transmit inhibitory signals to other nerve cells. Given the wide distribution of GABA throughout the brain (more than 30% of all central synapses in mammals are GABAergic), it is not surprising that GABA-mediated neurotransmission plays an important role not only in the control of various brain functions but also, as reviewed in this chapter, in the pathophysiology of several mental and neurological conditions including anxiety, sleep disorders, epilepsy, and Huntington’s chorea. Recent insights into the structure, function, and pharmacology of GABA receptors have contributed substantially to the identification of key neurobiological and neurochemical mechanisms that underlie the regulation of neuronal excitability and of emotional and behavioral states. They have also facilitated the development as well as characterization of the mechanisms of action of therapeutic agents used in the treatment of GABA-related pathologies