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In order to investigate roles of dopamine receptor subtypes in reward-based learning, we examined choice behavior of dopamine D1 and D2 receptor-knockout (D1R-KO and D2R-KO, respectively) mice in an instrumental learning task with progressively increasing reversal frequency and a dynamic two-armed bandit task. Performance of D2R-KO mice was progressively impaired in the former as the frequency of reversal increased and profoundly impaired in the latter even with prolonged training, whereas D1R-KO mice showed relatively minor performance deficits. Choice behavior in the dynamic two-armed bandit task was well explained by a hybrid model including win-stay-lose-switch and reinforcement learning terms. A model-based analysis revealed increased win-stay, but impaired value updating and decreased value-dependent action selection in D2R-KO mice, which were detrimental to maximizing rewards in the dynamic two-armed bandit task. These results suggest an important role of dopamine D2 receptors in learning from past choice outcomes for rapid adjustment of choice behavior in a dynamic and uncertain environment.

The striatum is critically involved in value-based decision making. However, it is unclear how striatal direct and indirect pathways work together to make optimal choices in a dynamic and uncertain environment. Here, we examined the effects of selectively inactivating D1 receptor (D1R)- or D2 receptor (D2R)-expressing dorsal striatal neurons (corresponding to direct- and indirect-pathway neurons, respectively) on mouse choice behavior in a reversal task with progressively increasing reversal frequency and a dynamic two-armed bandit task. Inactivation of either D1R- or D2R-expressing striatal neurons impaired performance in both tasks, but the pattern of altered choice behavior differed between the two animal groups. A reinforcement learning model-based analysis indicated that inactivation of D1R- and D2R-expressing striatal neurons selectively impairs value-dependent action selection and value learning, respectively. Our results suggest differential contributions of striatal direct and indirect pathways to two distinct steps in value-based decision making.

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