Chloride cotransporters, chloride homeostasis, and synaptic inhibition in the developing auditory system

The role of glycine and GABA as inhibitory neurotransmitters in the adult vertebrate nervous system has been well characterized in a variety of model systems, including the auditory, which is particularly well suited for analyzing inhibitory neurotransmission. However, a full understanding of glycinergic and GABAergic transmission requires profound knowledge of how the precise organization of such synapses emerges. Likewise, the role of glycinergic and GABAergic signaling during development, including the dynamic changes in regulation of cytosolic chloride via chloride cotransporters, needs to be thoroughly understood. Recent literature has elucidated the developmental expression of many of the molecular components that comprise the inhibitory synaptic phenotype. An equally important focus of research has revealed the critical role of glycinergic and GABAergic signaling in sculpting different developmental aspects in the auditory system. This review examines the current literature detailing the expression patterns and function (chapter 1), as well as the regulation and pharmacology of chloride cotransporters (chapter 2). Of particular importance is the ontogeny of glycinergic and GABAergic transmission (chapter 3). The review also surveys the recent work on the signaling role of these two major inhibitory neurotransmitters in the developing auditory system (chapter 4) and concludes with an overview of areas for further research (chapter 5).

► Regulation of neuronal Cl- concentration by Cl- cotransporters.
► Expression, function, regulation, and pharmacology of neuronal Cl- cotransporters.
► Cl- cotransporter activity in the auditory brainstem.
► GABA and glycine signaling in the developing auditory system.