PREFRONTAL VIP INTERNEURONS REGULATE BEHAVIORAL UPDATING DURING REVERSAL LEARNING

To gain insight into neural mechanisms supporting behavioral flexibility in dynamic environments, we examined roles of VIP neurons in mouse medial prefrontal cortex (mPFC) in probabilistic reversal learning. Behaviorally, manipulating VIP neuronal activity left probabilistic classical conditioning unaffected but severely impaired reversal learning. Physiologically, conditioned cue-associated VIP neuronal responses changed abruptly after encountering an unexpected reward. They also conveyed strong reward prediction error signals during behavioral reversal, but not before or after, unlike pyramidal neurons which consistently conveyed error signals throughout all phases. Notably, the signal’s persistence across trials correlated with reversal learning duration. Inhibiting VIP neurons selectively disrupted reversal-related activity and cue preference remapping in pyramidal neurons, indicating that VIP-dependent circuit modulation is required for dynamic updating of cue–outcome representations. These results suggest that mPFC VIP neurons play crucial roles in rapid reversal learning, but not in gradual value updating under stable probabilistic contingencies, by monitoring salient deviations from ongoing environmental contingencies and imposing error-correction signals during behavioral adjustments. These findings reveal a circuit mechanism by which inhibitory interneurons support flexible behavior in complex environments.