Direct Pathway Neurons in the Mouse Ventral Striatum Are Active During Goal-Directed Action but Not Reward Consumption During Operant Conditioning

These findings suggest that direct pathway neurons in the VS contribute to decision-making in learned action-outcome associations, indicating a specialized role in initiating operant behaviors.

Here, we introduce an operant conditioning paradigm using open-source microcontrollers to train mice in three sequential learning phases. Phase I employs classical conditioning, associating a 5 s sound cue (CS) with a sucrose-water reward. In Phase II, the CS is replaced by a lever press as the requirement for reward delivery, marking an operant conditioning stage. Phase III combines these elements, requiring mice to press the lever during the CS to obtain the reward. We recorded calcium signals from direct pathway spiny projection neurons (dSPNs) in the VS throughout the three phases of training.

We find that dSPNs are specifically engaged when the mouse makes a decision to perform a reward-seeking action in response to a CS but are largely inactive during actions taken outside the CS. Conclusions: These findings suggest that direct pathway neurons in the VS contribute to decision-making in learned action-outcome associations, indicating a specialized role in initiating operant behaviors.