In addition to fast GABAA receptor-mediated conductances, GABA activates G-protein coupled GABAB receptors that cause slow (100–500 ms) postsynaptic inhibition by opening inwardly rectifying K+ (GIRK) channels (Luscher et al., 1997). Postsynaptic GABAB receptors also inhibit voltage-gated calcium channels, thereby, for example, reducing dendritic excitability (Perez-Garci et al., 2006). Furthermore, GABAB receptors are present on both glutamatergic and GABAergic nerve terminals where their activation causes presynaptic inhibition of transmitter release (Bowery, 1993). Curiously, while inhibitory actions of GABAB receptors have been well characterized in brain slices, few in vivo studies have probed the role of slow GABAB receptor mediated transmission in cortical function. Although transgenic mice lacking functional GABAB receptors are prone to spontaneous epileptic seizures (Schuler et al., 2001), the contribution of GABAB receptor signaling to spontaneous or sensory-evoked cortical activity is unclear. It has been suggested that synaptically released GABA from a large number of co-active interneurons must be pooled or accumulated to activate GABAB receptors (Isaacson et al., 1993; Scanziani, 2000). Since the conditions in which spontaneous or sensory-evoked cortical activity in vivo drives GABAB-mediated responses remain to be established, it is simplest to interpret cortical inhibition as largely reflecting the actions of ionotropic GABAA receptors.
