Dorsal raphe dopamine neurons signal motivational salience dependent on internal and external states

The ability to recognize motivationally salient events and respond to them adaptively is critical for survival. Here we tested whether dopamine (DA) neurons in the dorsal raphe nucleus (DRN) contribute to this process. Population recordings of DRN DA neurons during associative learning tasks showed that their activity dynamically tracks salience, developing excitation to both reward- and punishment-paired cues. The DRN DA response to reward-predicting cues was diminished after satiety, suggesting modulation by internal states. DRN DA activity was also greater for unexpected outcomes than for expected outcomes. Two-photon imaging of DRN DA neurons demonstrated that the majority of individual neurons developed activation to reward-predicting cues but not to punishment-predicting cues, which was surprising and qualitatively distinct from the population results. Head-fixation during fear learning abolished the neural response to aversive cues, indicating modulation by behavioral context. Overall, these results suggest that DRN DA neurons encode motivational salience, dependent on internal and external factors.