Neuron
Volume 89, Issue 6, 16 March 2016, Pages 1157-1172
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Review
Chloride Regulation: A Dynamic Equilibrium Crucial for Synaptic Inhibition

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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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