Regulation of Excitability by Extrasynaptic GABAA Receptors

Chapter
First Online:
Part of the Results and Problems in Cell Differentiation book series (RESULTS, volume 44)

Abstract

Not only are GABAA receptors activated transiently by GABA released at synapses, but high affinity, extrasynaptic GABAA receptors are also activated by ambient, extracellular GABA as a more persistent form of signalling (often termed tonic inhibition). Over the last decade tonic GABAA receptor-mediated inhibition and the properties of GABAA receptors mediating this signalling have received increasing attention. Tonic inhibition is present throughout the central nervous system, but is expressed in a cell-type specific manner (e.g. in interneurons more so than in pyramidal cells in the hippocampus, and in thalamocortical neurons more so than in reticular thalamic neurons in the thalamus). As a consequence, tonic inhibition can have a complex effect on network activity. Tonic inhibition is not fixed but can be modulated by endogenous and exogenous modulators, such as neurosteroids, and by developmental, physiological and pathological regulation of GABA uptake and GABAA receptor expression. There is also growing evidence that tonic currents play an important role in epilepsy, sleep (also actions of anaesthetics and sedatives), memory and cognition. Therefore, drugs specifically aimed at targeting the extrasynaptic receptors involved in tonic inhibition could be a novel approach to regulating both physiological and pathological processes.

Keywords

Pyramidal Cell GABAA Receptor Tonic Inhibition Gaba Transporter Gaba Uptake 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Copyright information

© Springer-Verlag Berlin Heidelberg 2007

Authors and Affiliations

  1. 1.Institute of NeurologyUniversity College LondonLondonUK
  2. 2.RIKEN Brain Science InstituteSaitamaJapan
  3. 3.Nizhny Novgorod State UniversityNizhny NovgorodRussia

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