title: Chloride Regulation: A Dynamic Equilibrium Crucial for Synaptic Inhibition.
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.
authors.affiliation: Institut Universitaire en Santé Mentale de Québec, Québec, QC G1J 2G3, Canada; Department of Mathematics and Statistics, Université Laval, Québec, QC G1V 0A6, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Doyon
authors.affiliation: Team P3M, Institut de Neurosciences de la Timone, UMR 7289, CNRS and Aix Marseille Université, F-13385 Marseille, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Vinay
authors.affiliation: 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.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Prescott
authors.affiliation: 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: yves.dekoninck@neuro.ulaval.ca.
authors.forename: Yves
authors.initials: Y
authors.lastname: De Koninck
mesh_terms: D000818:Animals; D002712:Chlorides / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D009433:Neural Inhibition / Q000502:physiology*; D017711:Nonlinear Dynamics; D013569:Synapses / Q000502:physiology*
chemical_list: D002712:Chlorides