Dopamine receptor activation regulates reward expectancy signals during cognitive control in primate prefrontal neurons

Dopamine neurons respond to reward-predicting cues but also modulate information processing in the prefrontal cortex essential for cognitive control. Whether dopamine controls reward expectation signals in prefrontal cortex that motivate cognitive control is unknown. We trained two male macaques on a working memory task while varying the reward size earned for successful task completion. We recorded neurons in lateral prefrontal cortex while simultaneously stimulating dopamine D1 receptor (D1R) or D2 receptor (D2R) families using micro-iontophoresis. We show that many neurons predict reward size throughout the trial. D1R stimulation showed mixed effects following reward cues but decreased reward expectancy coding during the memory delay. By contrast, D2R stimulation increased reward expectancy coding in multiple task periods, including cueing and memory periods. Stimulation of either dopamine receptors increased the neurons’ selective responses to reward size upon reward delivery. The differential modulation of reward expectancy by dopamine receptors suggests that dopamine regulates reward expectancy necessary for successful cognitive control. Dopamine responds to reward-predicting cues and is also linked to cognitive control. Here the authors examine the role of dopamine receptor subtypes in the neuromodulation of reward-related activity in the macaque prefrontal cortex.