The study investigates the role of the lateral habenula in modulating dopamine neurons' responses to reward-related stimuli. Using a visually guided saccade task with positionally biased reward outcomes in rhesus monkeys, the researchers found that lateral habenula neurons were excited by no-reward-predicting targets and inhibited by reward-predicting targets. In contrast, dopamine neurons were excited by reward-predicting targets and inhibited by no-reward-predicting targets. The responses of both neuronal populations reversed when the position-reward contingency was changed. Additionally, weak electrical stimulation of the lateral habenula inhibited dopamine neurons, suggesting that the lateral habenula plays a crucial role in determining the reward-related activity of dopamine neurons. These findings indicate that the lateral habenula is a key source of negative reward signals in dopamine neurons, contributing to the brain's reward system.The study investigates the role of the lateral habenula in modulating dopamine neurons' responses to reward-related stimuli. Using a visually guided saccade task with positionally biased reward outcomes in rhesus monkeys, the researchers found that lateral habenula neurons were excited by no-reward-predicting targets and inhibited by reward-predicting targets. In contrast, dopamine neurons were excited by reward-predicting targets and inhibited by no-reward-predicting targets. The responses of both neuronal populations reversed when the position-reward contingency was changed. Additionally, weak electrical stimulation of the lateral habenula inhibited dopamine neurons, suggesting that the lateral habenula plays a crucial role in determining the reward-related activity of dopamine neurons. These findings indicate that the lateral habenula is a key source of negative reward signals in dopamine neurons, contributing to the brain's reward system.