Distinct roles for direct and indirect pathway striatal neurons in reinforcement

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Abstract
Cell type–specific expression and activation of channelrhodopsin-2 in the dorsomedial striatum shows that stimulation of dopamine D1 receptor–expressing direct pathway medium spiny neurons (MSNs) can reinforce operant behavior in awake behaving mice, whereas activation of D2 receptor–expressing indirect pathway MSNs punishes operant behavior. Dopamine signaling is implicated in reinforcement learning, but the neural substrates targeted by dopamine are poorly understood. We bypassed dopamine signaling itself and tested how optogenetic activation of dopamine D1 or D2 receptor–expressing striatal projection neurons influenced reinforcement learning in mice. Stimulating D1 receptor–expressing neurons induced persistent reinforcement, whereas stimulating D2 receptor–expressing neurons induced transient punishment, indicating that activation of these circuits is sufficient to modify the probability of performing future actions.