Distinct Functions of the Primate Putamen Direct and Indirect Pathways in Adaptive Outcome-Based Action Selection

Cortico-basal ganglia circuits are critical regulators of reward-based decision making.Reinforcement learning models posit that action reward value is encoded by thefiring activity of striatal medium spiny neurons (MSNs) and updated upon changingreinforcement contingencies by dopamine (DA) signaling to these neurons. However,it remains unclear how the anatomically distinct direct and indirect pathways throughthe basal ganglia are involved in updating action reward value under changingcontingencies. MSNs of the direct pathway predominantly express DA D1 receptorsand those of the indirect pathway predominantly D2 receptors, so we tested fordistinct functions in behavioral adaptation by injecting D1 and D2 receptor antagonistsinto the putamen of two macaque monkeys performing a free choice task forprobabilistic reward. In this task, monkeys turned a handle toward either a left or righttarget depending on an asymmetrically assigned probability of large reward. Rewardprobabilities of left and right targets changed after 30–150 trials, so the monkeys wererequired to learn the higher-value target choice based on action–outcome history. In thecontrol condition, the monkeys showed stable selection of the higher-value target (thatmore likely to yield large reward) and kept choosing the higher-value target regardlessof less frequent small reward outcomes. The monkeys also made flexible changes ofselection away from the high-value target when two or three small reward outcomesoccurred randomly in succession. DA D1 antagonist injection significantly increased theprobability of the monkey switching to the alternate target in response to successivesmall reward outcomes. Conversely, D2 antagonist injection significantly decreased theswitching probability. These results suggest distinct functions of D1 and D2 receptormediatedsignaling processes in action selection based on action–outcome history, withD1 receptor-mediated signaling promoting the stable choice of higher-value targets andD2 receptor-mediated signaling promoting a switch in action away from small rewardFrontiers in Neuroanatomy | www.frontiersin.org 1 August 2017 | Volume 11 | Article 66Ueda et al. D1, D2 Receptor Blockageoutcomes. Therefore, direct and indirect pathways appear to have complementaryfunctions in maintaining optimal goal-directed action selection and updating action value,which are dependent on D1 and D2 DA receptor signalin