Opposite initialization to novel cues in dopamine signaling in ventral and posterior striatum in mice

Abstract

Dopamine neurons are thought to encode novelty in addition to reward prediction error (the discrepancy between actual and predicted values). In this study, we compared dopamine activity across the striatum using fiber fluorometry in mice. During classical conditioning, we observed opposite dynamics in dopamine axon signals in the ventral striatum (‘VS dopamine’) and the posterior tail of the striatum (‘TS dopamine’). TS dopamine showed strong excitation to novel cues, whereas VS dopamine showed no responses to novel cues until they had been paired with a reward. TS dopamine cue responses decreased over time, depending on what the cue predicted. Additionally, TS dopamine showed excitation to several types of stimuli including rewarding, aversive, and neutral stimuli whereas VS dopamine showed excitation only to reward or reward-predicting cues. Together, these results demonstrate that dopamine novelty signals are localized in TS along with general salience signals, while VS dopamine reliably encodes reward prediction error.

DOI: http://dx.doi.org/10.7554/eLife.21886.001

eLife digest

New experiences trigger a variety of responses in animals. We are surprised by, move towards, and often explore new objects. But how does the brain control these responses?

Dopamine is a molecule that controls many processes in the brain and plays critical roles in various mental disorders, diseases that affect movement, and addiction. Rewarding experiences (like a glass of cold water on a hot day) can trigger dopamine neurons and studies have also shown that dopamine neurons respond to new experiences. This suggested that novelty may be rewarding in itself, or that novelty may signal the potential for future reward. On the other hand, it may be that different groups of dopamine neurons play different roles in responding to new or rewarding experiences.

In 2015, it was reported that dopamine neurons connected to the rear part of an area in the brain called the striatum receive signals from different parts of the brain than most other dopamine neurons. The dopamine neurons connected to this “tail” of the striatum preferentially received inputs from regions involved in arousal rather than reward, suggesting that they may have a unique role and transmit a different type of information.

Now, Menegas et al. have shown that dopamine signals in different areas of the striatum separate reward from novelty and other signals in mice. The results demonstrate that new odors activate dopamine neurons projecting to the tail of the striatum, but that this activity fades as the novelty wears off (as the mice learn to associate the odor with a particular outcome). By contrast, dopamine neurons projecting to the front of the striatum do not respond to novelty, but rather become more active as mice learn which odors accompany rewards (only responding to odors that predict reward). The experiments also show that dopamine neurons in the tail of the striatum encode information about the importance of a stimulus.

Together, these findings indicate that some of the roles dopamine plays in the brain may not be related to reward, but are instead linked to the novelty and importance of the stimulus. The next challenge will be to find out how the separate reward and novelty signals in dopamine neurons relate to the animals’ behavior. This may help us to better understand dopamine-related psychiatric conditions, such as depression and addiction.

DOI: http://dx.doi.org/10.7554/eLife.21886.002