Modulation of dopamine neurons alters behavior and event encoding in the nucleus accumbens during Pavlovian conditioning

When a cue is located away from its associated reward, some animals will learn to approach the site of reward (goal-tracking behavior) while others will approach the cue (sign-tracking behavior). The acquisition of sign tracking, but not goal tracking, is dependent on dopamine in the nucleus accumbens (NAc), and we have previously demonstrated that reward-evoked activity in the NAc core may reflect different patterns of dopamine release in sign tracker vs. goal tracker individuals. However, a causal relationship among dopamine release, NAc activity, and sign tracking has not been established. Using male and female TH::Cre rats, we expressed inhibitory or excitatory opsins in dopamine neurons of the ventral tegmental area (VTA) and examined the impact of optical manipulation of dopamine neurons on behavior and concurrent NAc neuronal activity. We found that inhibition of VTA dopamine neurons at the time of reward suppressed the acquisition of sign-tracking, but not goal-tracking, behavior. On the other hand, stimulation of dopamine neurons did not alter the acquisition of sign tracking; however, cessation of stimulation impeded further acquisition of sign tracking. Finally, both inhibition and stimulation of VTA dopamine neurons rapidly modulated activity in a subset of NAc neurons and led to changes in cue- and reward-related activity across sessions. Overall, these findings support the ideas that sign tracking and goal tracking are the products of two different learning processes – one dopamine-dependent and one not – and that the impact of VTA dopamine on sign tracking may be mediated by activity in the NAc core. Significance Statement During Pavlovian reward conditioning, activity patterns in the nucleus accumbens (NAc) core appear to reflect differences in dopamine release between sign trackers – individuals who tend to approach reward-paired cues – and goal trackers, who tend to approach the site of reward. Here, we use optogenetics to inhibit or stimulate dopamine neurons at the time of reward during learning. We show that inhibition suppresses the acquisition of sign-tracking behavior but not goal-tracking behavior; meanwhile, stimulation has no overt effect, but cessation of stimulation suppresses further acquisition of sign tracking, but not goal tracking. Finally, by recording from individual neurons concurrent with optical stimulation/inhibition, we show that these effects may be mediated by a small subset of neurons in the NAc core.