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

Abstract

Midbrain dopamine neurons are key components of the brain’s reward system1, which is thought to guide reward-seeking behaviours2,3,4. Although recent studies have shown how dopamine neurons respond to rewards and sensory stimuli predicting reward1,5,6, 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 outcomes7. 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 suggest that the inhibitory input from the lateral habenula plays an important role in determining the reward-related activity of dopamine neurons.

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Figure 1: Behavioural task and monkey’s performance.
Figure 2: Activity of habenula neurons during the reward-biased visual saccade task.
Figure 3: Reward modulation of lateral habenula neurons and dopamine neurons.
Figure 4: Effects of electrical stimulation of the lateral habenula on dopamine neurons.

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Acknowledgements

We thank R. H. Wurtz, B. J. Richmond, K. Nakamura, L. Ding, M. Isoda, S. Hong and E. Bromberg-Martin for discussions, M. K. Smith for histological expertise, and J. W. McClurkin, A. M. Nichols, T. W. Ruffner, A. V. Hays and L. P. Jensen for technical assistance. This research was supported by the Intramural Research Program at the National Institutes of Health, National Eye Institute.

Author Contributions M.M. performed the experiments and analysed the data. M.M. and O.H. discussed the results and wrote the manuscript. O.H. organized this project.

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Correspondence to Okihide Hikosaka.

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Matsumoto, M., Hikosaka, O. Lateral habenula as a source of negative reward signals in dopamine neurons. Nature 447, 1111–1115 (2007). https://doi.org/10.1038/nature05860

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