Regulation of GABA(A) receptor membrane trafficking and synaptic localization

Abstract

Synaptic inhibition plays a key role in regulating neuronal excitability and information processing in the brain. The strength of synaptic inhibition is therefore an important determinant of both cellular and network activity levels in the central nervous system (CNS). gamma-aminobutyric acid type A (GABA(A)) receptors are the major sites for fast inhibitory neurotransmission in the CNS and alterations in their trafficking, synaptic accumulation and function play a key role in regulating neuronal excitability. Synaptic receptor number is determined by the trafficking of GABA(A) receptors to and away from inhibitory synapses and by their stability and localization at the inhibitory postsynaptic domain. Here we discuss advances that have led to an improved understanding of the mechanisms that regulate the delivery and stabilization of GABA(A) receptors at inhibitory synapses and address the role of GABA(A) receptor trafficking, GABA(A) receptor associated proteins and post-translational modifications in regulating this process.