Lateral habenula as a source of negative reward signals in dopamine neurons

Rewarding behaviour The involvement of dopaminergic neurons in motor symptoms is evident from their role in Parkinson's disease. Yet the neurons that release dopamine carry signals related to rewards, not body movements. As a solution to this puzzle, recent theories suggest that the reward-related dopamine signals are used for learning of motor behaviours. Until now it has been unclear how dopamine neurons acquire the reward-related signals. Now in an experiment in rhesus monkeys performing a visually guided task for reward, Masayuki Matsumoto and Okihide Hikosaka show that a small brain area called the lateral habenula controls dopamine neurons by inhibiting them and thereby suppressing less rewarding eye movements. This discovery opens up possibilities for new research on the links between emotion, motivation and motor behaviours. Neurons in the primate lateral habenula are shown to have reward-related activity that apparently signals the inverse to the dopamine response. Stimulation of lateral habenula suppresses dopamine neurons, suggesting that this area plays a role in shaping reward signals. Midbrain dopamine neurons are key components of the brain’s reward system 1 , which is thought to guide reward-seeking behaviours 2 , 3 , 4 . Although recent studies have shown how dopamine neurons respond to rewards and sensory stimuli predicting reward 1 , 5 , 6 , it is unclear which parts of the brain provide dopamine neurons with signals necessary for these actions. Here we show that the primate lateral habenula, part of the structure called the epithalamus, is a major candidate for a source of negative reward-related signals in dopamine neurons. We recorded the activity of habenula neurons and dopamine neurons while rhesus monkeys were performing a visually guided saccade task with positionally biased reward outcomes 7 . Many habenula neurons were excited by a no-reward-predicting target and inhibited by a reward-predicting target. In contrast, dopamine neurons were excited and inhibited by reward-predicting and no-reward-predicting targets, respectively. Each time the rewarded and unrewarded positions were reversed, both habenula and dopamine neurons reversed their responses as the bias in saccade latency reversed. In unrewarded trials, the excitation of habenula neurons started earlier than the inhibition of dopamine neurons. Furthermore, weak electrical stimulation of the lateral habenula elicited strong inhibitions in dopamine neurons. These results sug