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 GABAA 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.