Topography of reward and aversion encoding in the mesolimbic dopaminergic system

Abstract

Dopamine (DA) neurons in the VTA play essential roles in adaptive motivated behavior, which requires rapid discrimination between positive and negative motivational signature. However, the precise functional DA circuitry processing reward and aversive information remain elusive. Here, we report that the encoding of reward and aversion by the DA system in the NAc is tightly associated with its anatomical location. By recording the dynamics of DA release with genetically encoded fluorescent DA sensor using in vivo fiber photometry in freely moving male mice, we found that the DA-sensor signal in the dorsomedial NAc shell and dorsolateral NAc shell were increased during rewarding events and decreased during aversive noxious events. In contrast, the release of DA in the ventromedial NAc shell was increased by both rewarding and aversive stimuli, whereas the DA-sensor signal in the central ventromedial NAc shell and ventrolateral NAc shell showed complex dynamics. Furthermore, the activity of DA fibers in different subregions of NAc measured with calcium sensor largely recapitulated the changes of DA-sensor signal in response to rewarding and aversive stimuli. In addition, correlation analysis showed that the response magnitude of DA-sensor or fibers significantly changed along the DV axis of the NAc. These results revealed the distinct role of the mesolimbic DA system in different subregions of NAc in encoding value and salience.