Phasic GABAA-Mediated Inhibition

Excerpt

Phasic inhibition consists of fast GABA_A-mediated inhibitory postsynaptic potentials (IPSPs) regulating point to point communication between neurons. In physiological conditions it exerts a powerful control on cell excitability and network oscillations thought to be associated with high cognitive functions. GABA_A receptors facing the presynaptic release sites are exposed, for a brief period of time, to high concentration of GABA released by exocytosis of presynaptic vesicles. Once released, GABA diffuses throughout the neuropil before being taken up by selective plasma membrane transporters which contribute to its clearance. In this Chapter different steps contributing to shape synaptic currents, including vesicle exocytosis, dynamics of GABA transient in the synaptic cleft, postsynaptic receptors and GABA transporters will be highlighted. Particular attention will be paid to the regulation of GABA release by the calcium-induced calcium release process and by presynaptic GABA_A and/or GABA_B receptors. Finally, the heterogeneity of GABA_A receptor subunits will be discussed in relation to their ability to give rise to a variety of functional GABA_A receptors, differently regulated by endogenous or exogenous molecules useful for the treatment of severe neurological and psychiatric disorders.