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Inhibitory Regulation of Excitatory Neurotransmission pp 29–48Cite as

Regulation of Excitability by Extrasynaptic GABAA Receptors

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Part of the book series: Results and Problems in Cell Differentiation ((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.

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Authors and Affiliations

  1. Institute of Neurology, University College London, Queen Square, WC1N 2BG, London, UK

    Matthew C. Walker

  2. RIKEN Brain Science Institute, 2–1 Hirosawa, Wako-shi, 351-0198, Saitama, Japan

    Alexey Semyanov

  3. Nizhny Novgorod State University, Nizhny Novgorod, Russia

    Alexey Semyanov

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Correspondence to Matthew C. Walker .

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Mark G. Darlison

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© 2007 Springer-Verlag Berlin Heidelberg

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Walker, M.C., Semyanov, A. (2007). Regulation of Excitability by Extrasynaptic GABAA Receptors. In: Darlison, M.G. (eds) Inhibitory Regulation of Excitatory Neurotransmission. Results and Problems in Cell Differentiation, vol 44. Springer, Berlin, Heidelberg. https://doi.org/10.1007/400_2007_030

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