Neuronal chloride and excitability - the big impact of small changes

Synaptic inhibition is a critical regulator of neuronal excitability, and in the mature brain the majority of synaptic inhibition is mediated by Cl^--permeable GABA_A receptors. Unlike other physiologically relevant ions, Cl^- is dynamically regulated, and alterations in the Cl^- gradient can have significant impact on neuronal excitability. Due to changes in the neuronal Cl^- concentration, GABAergic transmission can bidirectionally regulate the induction of excitatory synaptic plasticity and gate the closing of the critical period for monocular deprivation in visual cortex. GABAergic circuitry can also provide a powerful restraining mechanism for the spread of excitation, however Cl^- extrusion mechanisms can become overwhelmed and GABA can paradoxically contribute to pathological excitation such as the propagation of seizure activity.