Subthalamic Nucleus dynamically encodes reward value and cognitive flexibility

Abstract

The subthalamic nucleus (STN) is classically associated with motor control but is increasingly recognised as a key component of the neural circuits underlying cognition. However, how the STN encodes learned reward associations and updates these representations when environmental contingencies change remains unclear. Here, we combined fibre photometry calcium imaging and chemogenetic inhibition to identify the contribution of the STN in reward learning and cognitive flexibility. During established Pavlovian conditioning, calcium imaging of the STN showed distinctive responses to reward predictive cue and reward delivery, while no response was detected to unrewarded cues. Upon reversal of reward predictive cues, STN activity initially remained associated with the previously rewarded cue before remapping to the newly rewarded cue as animals acquired the updated contingency. Chemogenetic inhibition of the STN impaired cue discrimination on established Pavlovian conditioning, delayed reversal learning, and disrupted outcome-specific Pavlovian-to-instrumental transfer. Together these results demonstrate that STN activity is required for flexible updating of learned reward associations and goal-directed behaviour. These findings establish the STN as a dynamic integrative hub that encodes and updates learned reward representations to support cognitive flexibility, extending its role beyond motor control to include goal-directed behaviour. We show STN activity tracks reward-predictive cues and updates when contingencies reverse. Overall, these findings demonstrate that the STN is not just downstream of cortical control but actively supports updating of reward associations.