The VTA is modulated by excitatory glutamatergic inputs arising from the PFC, bed nucleus of the stria terminalis, amygdala, pontomesencephalic tegmental nuclei (Mao and McGehee, 2010), and by a large population of inhibitory GABAergic interneurons (Johnson and North, 1992; Theile et al., 2008) and afferents that arise from heterogeneous sources (Geisler and Zahm, 2005). There are several different nAChR subunits expressed in the VTA, some of which are the α3, α4, α5, α6, α7, β2, and β3 subtypes (Azam et al., 2002; Perry et al., 2002; Yang et al., 2009). The α4 and β2 mRNAs are expressed in nearly all DAergic and GABAergic VTA neurons, while α7 mRNA is distributed in only 40% of these neurons (Nashmi and Lester, 2006). The α7* nAChRs are most densely localized on pre-synaptic glutamatergic, but not cholinergic, terminals in the VTA (see Figure 2) (Klink et al., 2001; Jones and Wonnacott, 2004).
