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 versus 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.