Tonically active GABA A receptors: modulating gain and maintaining the tone

GABA A receptors not only respond to the local release of GABA from presynaptic terminals, but can also mediate a persistent ‘tonic current’. This reflects the activation of high-affinity GABA A receptors by ambient GABA concentrations. Tonic GABA A-receptor-mediated signalling occurs in different brain regions, shows cell-type-specific differences in magnitude and pharmacology, and changes during brain development. Some clues to the adaptive significance of this phenomenon are beginning to emerge: in cerebellar granule cells, it alters the gain of transmission of rate-coded sensory information; in the hippocampus, it acts in a cell-type-specific manner to regulate the excitability of the network. Because tonic conductances can be modulated by changes in GABA release and uptake, and by modulators of high-affinity GABA A receptors including neurosteroids, this phenomenon provides a potentially important new window onto neuronal information processing and pathological states such as epilepsy.