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Chloride Regulation: A Dynamic Equilibrium Crucial for Synaptic Inhibition
Nicolas Doyon1, Laurent Vinay2, Steven A Prescott3
1Institut Universitaire en Santé Mentale de Québec, Québec, QC G1J 2G3, Canada; Department of Mathematics and Statistics, Université Laval, Québec, QC G1V 0A6, Canada.
Abstract:
Fast synaptic inhibition relies on tight regulation of intracellular Cl(-). Chloride dysregulation is implicated in several neurological and psychiatric disorders. Beyond mere disinhibition, the consequences of Cl(-) dysregulation are multifaceted and best understood in terms of a dynamical system involving complex interactions between multiple processes operating on many spatiotemporal scales. This dynamical perspective helps explain many unintuitive manifestations of Cl(-) dysregulation. Here we discuss how taking into account dynamical regulation of intracellular Cl(-) is important for understanding how synaptic inhibition fails, how to best detect that failure, why Cl(-) regulation is energetically so expensive, and the overall consequences for therapeutics.
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