Fritschy_2012_Cell.Mol.Life.Sci_69_2485

Knowledge of the functional organization of the GABAergic system the main inhibitory neurotransmitter system in the CNS has increased remarkably in recent years In particular substantial progress has been made in elucidating the molecular mechanisms underlying the formation and plasticity of GABAergic synapses Evidence available ascribes a key role to the cytoplasmic protein gephyrin to form a postsynaptic scaffold anchoring GABA(A receptors along with other transmembrane proteins and signaling molecules in the postsynaptic density However the mechanisms of gephyrin scaffolding remain elusive notably because gephyrin can auto-aggregate spontaneously and lacks PDZ protein interaction domains found in a majority of scaffolding proteins In addition the structural diversity of GABA(A receptors which are pentameric channels encoded by a large family of subunits has been largely overlooked in these studies Finally the role of the dystrophin-glycoprotein complex present in a subset of GABAergic synapses in cortical structures remains ill-defined In this review we discuss recent results derived mainly from the analysis of mutant mice lacking a specific GABA(A receptor subtype or a core protein of the GABAergic postsynaptic density neuroligin-2 collybistin highlighting the molecular diversity of GABAergic synapses and its relevance for brain plasticity and function In addition we discuss the contribution of the dystrophin-glycoprotein complex to the molecular and functional heterogeneity of GABAergic synapses.