Tonically active GABA A receptors: modulating gain and maintaining the tone.
GABAA 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 GABAA receptors by ambient GABA concentrations. Tonic GABAA-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 GABAA receptors including neurosteroids, this phenomenon provides a potentially important new window onto neuronal information processing and pathological states such as epilepsy.
Semyanov
Alexey
A
Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK. a.semyanov@ion.ucl.ac.uk
Walker
Matthew C
MC
Kullmann
Dimitri M
DM
Silver
R Angus
RA
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000166:cytology*; D002478:Cells, Cultured; D008959:Models, Neurological; D009415:Nerve Net / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology; D009474:Neurons / Q000145:classification / Q000166:cytology / Q000502:physiology*; D017729:Presynaptic Terminals / Q000378:metabolism; D011963:Receptors, GABA-A / Q000145:classification / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid