[GABA.sub.A] receptor membrane trafficking regulates spine maturity

[GABA.sub.A] receptors ([GABA.sub.A]RS), the principal sites of synaptic inhibition in the brain, are dynamic entities on the neuronal cell surface, but the role their membrane trafficking plays in shaping neuronal activity remains obscure. Here, we examined this by using mutant receptor [beta]3 subunits ([beta]3S408/9A), which have reduced binding to the clathrin adaptor protein-2, a critical regulator of [GABA.sub.A]R endocytosis. Neurons expressing [beta]3S408/9A subunits exhibited increases in the number and size of inhibitory synapses, together with enhanced inhibitory synaptic transmission due to reduced [GABA.sub.A]R endocytosis. Furthermore, neurons expressing [beta]3S408/9A subunits had deficits in the number of mature spines and reduced accumulation of postsynaptic density protein-95 at excitatory synapses. This deficit in spine maturity was reversed by pharmacological blockade of [GABA.sub.A]Rs. Therefore, regulating the efficacy of synaptic inhibition by modulating [GABA.sub.A]R membrane trafficking may play a critical role in regulating spine maturity with significant implications for synaptic plasticity together with behavior. endocytosis | inhibition | phosphorylation