These findings suggest that salient sensory stimuli in the environment, such as those associated with rewards or drugs of abuse, would increase activity of PPTg cholinergic neurons, leading to increased phasic firing of DA neurons in the VTA (Maskos, 2008), while at the same time, decreasing the firing of tonically active cholinergic neurons in the NAc and striatum leading to a larger differential in DA release in response to phasic firing as compared to tonic firing (Exley and Cragg, 2008) (Figure 2). At the behavioral level, this conclusion is consistent with the finding that disruption of PPTg activity decreases the rewarding and locomotor effects of drugs of abuse such as cocaine and nicotine (Champtiaux et al., 2006; Corrigall et al., 1994; Corrigall et al., 2002), while lesion of NAc cholinergic neurons increases cocaine self-administration, as might be expected if a pause in cholinergic interneuron firing in NAc signals salience (Smith et al., 2004).
