Neural Circuit Mechanisms of Reward Prediction

When an animal learns that a conditioned stimulus (CS) predicts a reward, midbrain dopaminergic neurons become excited by the reward-predicting CS.  The neural circuits that generate this CS-elicited excitation are unknown.  We recorded the activity of identified dopaminergic neurons in the ventral tegmental area of mice in a classical conditioning task, in which odors or tones predicted different probabilities of reward or punishment.  During the task, we reversibly inactivated a region of the basal forebrain with a local infusion of muscimol, a GABAA receptor agonist.  Before basal forebrain inactivation, dopaminergic neurons were phasically excited by a reward-predicting CS.  Basal forebrain inactivation selectively eliminated this excitation.  These results suggest that information about reward-associated cues reaches dopaminergic neurons via the basal forebrain.