Chloride Regulation: A Dynamic Equilibrium Crucial for Synaptic Inhibition

Neuron. 2016 Mar 16;89(6):1157-1172. doi: 10.1016/j.neuron.2016.02.030.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Chlorides / metabolism*
  • Homeostasis / physiology
  • Humans
  • Models, Biological
  • Neural Inhibition / physiology*
  • Nonlinear Dynamics*
  • Synapses / physiology*

Substances

  • Chlorides