“Multiple Dopamine Systems: Weal and Woe of Dopamine”

Naoshige Uchida, Ph.D, Professor, Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University The ability to predict future reward and threat is critical for animals' survival so as to maximize rewards and minimize potential threats. Neurons that release dopamine (thereafter, dopamine neurons) are thought to play critical roles in learning from both reward and threat. However, the exact mechanisms remain controversial. Much of the work on dopamine neurons has been based on the dogma that dopamine neurons encode reward prediction errors (RPE = actual minus expected reward) and that they do so in a uniform manner. However, work from several groups, including ours, has indicated that dopamine neurons projecting to different targets exhibit distinct properties and serve distinct functions. Interestingly, dopamine neurons projecting to the posterior "tail" of the striatum (TS) differ in many ways from dopamine neurons projecting to the ventral striatum (VS) and other regions. VS-projecting dopamine neurons, which signal "canonical" RPEs, are activated by reward and inhibited by negative events. By contrast, TS-projecting dopamine neurons are activated by novel stimuli and by a subset of negative events. In this talk, I will discuss novel functions of TS-projecting dopamine neurons. These recent results point to the presence of multiple dopamine systems defined by their projection targets, which are different with regard to anatomy, activity and function.