Regulation of GABAA receptor trafficking, channel activity, and functional plasticity of inhibitory synapses

Neural inhibition in the brain is mainly mediated by ionotropic gamma-aminobutyric acid type A (GABA(A)) receptors. Different subtypes of these receptors, distinguished by their subunit composition, are either concentrated at postsynaptic sites where they mediate phasic inhibition or found at perisynaptic and extrasynaptic locations where they prolong phasic inhibition and mediate tonic inhibition, respectively. Of special interest are mechanisms that modulate the stability and function of postsynaptic GABA(A) receptor subtypes and that are implicated in functional plasticity of inhibitory transmission in the brain. We will summarize recent progress on the classification of synaptic versus extrasynaptic receptors, the molecular composition of the postsynaptic cytoskeleton, the function of receptor-associated proteins in trafficking of GABA(A) receptors to and from synapses, and their role in post-translational signaling mechanisms that modulate the stability, density, and function of GABA(A) receptors in the postsynaptic membrane. (C) 2004 Elsevier Inc. All rights reserved.