GABAA receptors can exist as either synaptic or extrasynaptic receptors that may facilitate rapid changes in inhibition. Most synaptic GABAA receptors are composed of two α, two β, and one γ subunit, where the γ subunit is located between an α and β subunit (Sieghart et al. 1999; Tretter et al. 1997) and contribute to synaptically mediated (phasic) inhibition. In contrast, tonic inhibition is due to highly sensitive GABAA receptors, activated by ambient extracellular GABA or from ‘spillover’ of GABA from synaptic signaling, thought to be in the range of 100 nM to 1 μM (Santhakumar et al. 2006; Tossman et al. 1986). The subunit composition of GABAA receptors at synaptic and extrasynaptic sites are thought to be different. Studies have shown that the α1 subunit is usually expressed in synaptic GABAA receptors while the α4 subunit predominantly occurs in extrasynaptic receptors (Mody 2001; Olsen and Sieghart 2009). GABAA receptor δ subunits are so far found to be exclusively present in extrasynaptic sites (Farrant and Nusser 2005). The α4 subunit has relatively low expression in the CNS (Wisden et al.
