Two types of dopamine neuron distinctly convey positive and negative motivational signals

Abstract

Dopamine neurons at the base of the brain are crucial for normal motor behaviour, and their loss leads to conditions such as Parkinson's disease. Yet the activity of dopamine neurons is not related to body movements, but to reward events. Recent theories suggest that dopamine neurons, as a homogeneous functional group, guide motor learning via reward-related signals. Now a study in monkeys undergoing Pavlovian conditioning to 'positive' and 'negative' stimuli shows that dopamine neurons are more heterogeneous than this model implies. Different groups of dopamine neurons, located in slightly different areas of the brain, have specific responses to pleasant and unpleasant stimuli, as well as to the trigger stimuli associated with these events. This suggests that dopamine neurons have a more complex involvement in learning control, encoding more subtle signals than simple reward. The observation that midbrain dopamine neurons are activated by reward, or sensory stimuli predicting reward, has led to the hypothesis that they encode value-related signals and are inhibited by aversive events. This is now shown to be true for only a subset of dopamine neurons; by recording neuronal activity in monkeys, dopamine neurons are found to be more heterogeneous than this model would suggest. Midbrain dopamine neurons are activated by reward or sensory stimuli predicting reward1,2,3,4. These excitatory responses increase as the reward value increases5. This response property has led to a hypothesis that dopamine neurons encode value-related signals and are inhibited by aversive events. Here we show that this is true only for a subset of dopamine neurons. We recorded the activity of dopamine neurons in monkeys (Macaca mulatta) during a Pavlovian procedure with appetitive and aversive outcomes (liquid rewards and airpuffs directed at the face, respectively). We found that some dopamine neurons were excited by reward-predicting stimuli and inhibited by airpuff-predicting stimuli, as the value hypothesis predicts. However, a greater number of dopamine neurons were excited by both of these stimuli, inconsistent with the hypothesis. Some dopamine neurons were also excited by both rewards and airpuffs themselves, especially when they were unpredictable. Neurons excited by the airpuff-predicting stimuli were located more dorsolaterally in the substantia nigra pars compacta, whereas neurons inhibited by the stimuli were located more ventromedially, some in the ventral tegmental area. A similar anatomical difference was observed for their responses to actual airpuffs. These findings suggest that different groups of dopamine neurons convey motivational signals in distinct manners.