THE DYNAMIC MODULATION OF GABAA RECEPTOR TRAFFICKING AND ITS ROLE IN REGULATING THE PLASTICITY OF INHIBITORY SYNAPSES

Vithlani M, Terunuma M, Moss SJ. The Dynamic Modulation of GABA(A) Receptor Trafficking and Its Role in Regulating the Plasticity of Inhibitory Synapses. Physiol Rev 91: 1009-1022, 2011; doi: 10.1152/physrev.00015.2010.-Inhibition in the adult mammalian central nervous system (CNS) is mediated by gamma-aminobutyric acid (GABA). The fast inhibitory actions of GABA are mediated by GABA type A receptors (GABA(A)Rs); they mediate both phasic and tonic inhibition in the brain and are the principle sites of action for anticonvulsant, anxiolytic, and sedative-hypnotic agents that include benzodiazepines, barbiturates, neurosteroids, and some general anesthetics. GABA(A)Rs are heteropentameric ligand-gated ion channels that are found concentrated at inhibitory postsynaptic sites where they mediate phasic inhibition and at extrasynaptic sites where they mediate tonic inhibition. The efficacy of inhibition and thus neuronal excitability is critically dependent on the accumulation of specific GABA(A)R subtypes at inhibitory synapses. Here we evaluate how neurons control the number of GABA(A)Rs on the neuronal plasma membrane together with their selective stabilization at synaptic sites. We then go on to examine the impact that these processes have on the strength of synaptic inhibition and behavior.