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 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.