Optogenetic stimulation or inhibition of dopamine neurons during Pavlovian conditioning alters behavior and event encoding in the nucleus accumbens
Authors: Ethan Herring, Kira Lear, Elin McLaughlin, Sandford Zeng, Eesha Patel, Tulasi Syamala, and Sara E. Morrison

 

If a Pavlovian cue predicts reward in a different location, some animals will preferentially approach and interact with the cue – a behavior known as sign tracking – while others will approach the site of reward delivery, a behavior known as goal tracking. Acquisition of sign tracking, but not goal tracking, depends on changes in dopamine release in the nucleus accumbens (NAc). We have previously demonstrated that reward-evoked activity in the NAc reflects what we know to be different patterns of dopamine release in sign trackers vs. goal trackers. However, it remains unclear whether there is a causal relationships among dopamine release, NAc neural activity, and sign tracking. Therefore, we used male and female TH (tyrosine hydroxylase)-Cre rats to express an excitatory or inhibitory opsin specifically in dopamine neurons of the ventral tegmental area (VTA). In order to target the dopaminergic reward prediction error signal, we stimulated or inhibited dopamine neurons at the time of reward delivery for the first several sessions of Pavlovian conditioning.

 

We found that inhibition of VTA dopamine neurons completely abolished the acquisition of sign tracking, but not goal tracking. Surprisingly, stimulation of dopamine neurons did not speed up or strengthen the acquisition of sign tracking, implying that there is a form of “gain control” in the mesolimbic dopamine system; however, removal of stimulation disrupted further acquisition of sign tracking (but not goal tracking) for several sessions. At the same time, we recorded from individual neurons in the NAc during either stimulation or inhibition of VTA dopamine neurons. We found that, in a subset of neurons, stimulation of dopamine neurons enhanced both excitatory and inhibitory responses to reward delivery, while inhibition primarily decreased the magnitude of excitatory reward responses. Meanwhile, inhibition at the time of reward prevented neural responses to the cue from increasing over the course of acquisition. Overall, these findings support the idea that sign tracking, but not goal tracking, depends upon dopaminergic reward signaling, which in turn promotes excitatory responses to both cue and reward in the NAc.