Journal
EUROPEAN JOURNAL OF NEUROSCIENCE
Volume 29, Issue 9, Pages 1779-1794Publisher
WILEY
DOI: 10.1111/j.1460-9568.2009.06716.x
Keywords
extrasynaptic receptors; genetically-engineered mice; insomnia; sedative-hypnotics; tonic inhibition
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Funding
- Forschungskredit from the University of Zurich
- European Union Marie Curie [MCRTN-CT-2004-512362]
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Most sedative-hypnotics used in insomnia treatment target the gamma-aminobutyric acid (GABA)(A) receptors. A vast repertoire of GABA(A) receptor subtypes has been identified and displays specific electrophysiological and functional properties. GABA(A)-mediated inhibition traditionally refers to 'phasic' inhibition, arising from synaptic GABA(A) receptors which transiently inhibit neurons. However, there is growing evidence that peri- or extra-synaptic GABA(A) receptors are continuously activated by low GABA concentrations and mediate a 'tonic' conductance. This slower type of signaling appears to play a key role in controlling cell excitability. This review aims at summarizing recent knowledge on GABA transmission, including the emergence of tonic conductance, and highlighting the importance of GABA(A) receptor heterogeneity. The mechanism of action of sedative-hypnotic drugs and their effects on sleep and the electroencephalogram will be reported. Furthermore, studies using genetically engineered mice will be emphasized, providing insights into the role of GABA(A) receptors in mechanisms underlying physiological and pharmacological sleep. Finally, we will address the potential of GABA(A) receptor pharmacology for the treatment of insomnia.
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