Cue-Evoked Dopamine Release Rapidly Modulates D2 Neurons in the Nucleus Accumbens During Motivated Behavior.

Successful reward procurement typically involves the completion of a goal-directed behavior in response to appropriate environmental cues. Although numerous studies link the mesolimbic dopamine system with these processes, how dopamine's effects are mediated on the receptor level within a key neural substrate, the nucleus accumbens, remains elusive. Here, we used a unique multimodal sensor that reveals three aspects of neuronal interactions: neurotransmitter release, cell firing, and dopamine-receptor type. We identified a key role of D2-like receptor (D2R)-expressing neurons in response to a reward-predicting cue, whereas both the D2R and D1R types modulate responses of neurons proximal to the goal-directed action. This work provides novel insight into the unique role of D2R-mediated neuronal activity to reward-associated cues, a fundamental aspect of motivated behaviors.