Building up the inhibitory synapse

Fast inhibitory transmission exerts a powerful control on neuronal excitability and network oscillations thought to be associated with high cognitive functions. An alteration of inhibitory signaling is associated with major neurological and psychiatric disorders including epilepsy. Once released from presynaptic nerve terminals, GABA and glycine cross the synaptic cleft and bind to postsynaptic receptors localized in precise apposition to presynaptic release sites. The functional organization of inhibitory synapses consists in a dynamic process which relies on a number of highly specialized proteins that ensure the correct targeting, clustering, stabilization and subsequent fate of synaptic receptors. Among the proteins involved in this task, the tubulin-binding protein gephyrin plays a crucial role. Through its self-oligomerization properties, this protein forms hexagonal lattices that trap GABAA and glycine receptors and link them to the cytoskeleton. By directly interacting with cell-adhesion molecules of the neuroligin-neurexin families that connect presynaptic and postsynaptic neurons at synapses, gephyrin ensures a backward control of presynaptic signaling. In addition, changes in clusters size is dynamically regulated by lateral diffusion of neurotransmitter receptors between the synaptic and extrasynaptic compartments and by their interaction with synaptic scaffold proteins.

The aim of this Research Topic (research articles and reviews) is to bring together experts on the cellular and molecular mechanisms regulating the appropriate assembly, location and function of pre and postsynaptic specializations at inhibitory synapses. A particular emphasis will be on the role of receptor trafficking in synaptic stabilization and plasticity.