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Neuron. 2016 Mar 16;89(6):1157-72. doi: 10.1016/j.neuron.2016.02.030.

Chloride Regulation: A Dynamic Equilibrium Crucial for Synaptic Inhibition.

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Institut Universitaire en Santé Mentale de Québec, Québec, QC G1J 2G3, Canada; Department of Mathematics and Statistics, Université Laval, Québec, QC G1V 0A6, Canada.
Team P3M, Institut de Neurosciences de la Timone, UMR 7289, CNRS and Aix Marseille Université, F-13385 Marseille, France.
Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Institut Universitaire en Santé Mentale de Québec, Québec, QC G1J 2G3, Canada; Department of Psychiatry and Neuroscience, Université Laval, Québec, QC, G1V 0A6, Canada. Electronic address:


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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