The tonic activation of extrasynaptic GABAA receptors by extracellular GABA provides a powerful means of regulating neuronal excitability. A consistent finding from studies that have used various models of temporal lobe epilepsy is that tonic GABAA receptor-mediated conductances are largely preserved in epileptic brain (in contrast to synaptic inhibition which is often reduced). Tonic inhibition is therefore an attractive target for antiepileptic drugs. However, the network consequences of a commonly used approach to augment tonic GABAA receptor-mediated conductances by global manipulation of extracellular GABA are difficult to predict without understanding how epileptogenesis alters the pharmacology and GABA sensitivity of tonic inhibition, and how manipulation of tonic conductances modulates the output of individual neurons. Here we review the current literature on epilepsy-associated changes in tonic GABAA receptor-mediated signalling, and speculate about possible effects they have at the network level. This article is part of the Special Issue entitled 'New Targets and Approaches to the Treatment of Epilepsy'.
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