Analysis of intact synapses indicated that while acute ethanol enhanced GABAergic transmission at synapses in several brain regions (Siggins et al., 2005; Weiner et al., 1997; Zhu and Lovinger, 2006), these effects often involved unexpected presynaptic potentiation (Ariwodola and Weiner, 2004; Carta et al., 2004; Nie et al., 2004; Roberto et al., 2003). The clearest evidence for enhanced GABA release at individual synapses comes from studies of isolated neurons from the cerebellum (Figures 2L and 2M) and basolateral amygdala (BLA) (Figures 2N and 2O) that include pinched-off, functional synaptic boutons that spontaneously release GABA. Ethanol potentiates this spontaneous release at concentrations relevant to intoxication. Indices of postsynaptic changes are not observed in the presence of ethanol (Kelm et al., 2007; Zhu and Lovinger, 2006), and this potentiation cannot result from activity of interneurons, as the boutons are no longer connected to somata. This type of experiment provides clear evidence of an increase in GABA release at central synapses.
