Executive control over incentive salience is essential to maintain goal-directed behaviour and the flexibility of stimulus–response associations. In rats, the prefrontal cortex (mainly prelimbic cortex, and some infralimbic cortex) sends glutamatergic projections directly to mesocortical dopamine neurons in the ventral tegmental area, thus exerting excitatory control over dopamine cell firing and dopamine release in the prefrontal cortex90 (for correspondence with humans, see figure 2). Given that ventral tegmental area dopamine cells project heavily to the basal ganglia, this frontal cortex glutamatergic projection might contribute to the development of incentive salience. Glutamatergic projections from the prefrontal cortex to the caudate and ventral striatum also modulate the control of the striatal-pallidal-thalamo-cortical system through both direct (D1 receptor-mediated) and indirect (D2 receptor-mediated) pathways. Thus, the prefrontal cortex is in a good position to regulate incentive salience and conditioned behaviour when a salient cue is presented to the individual.92,93
