Prefrontal dopamine activity is critical for rapid threat avoidance learning.

The medial prefrontal cortex (mPFC) is required for learning associations that determine whether animals approach or avoid potential threats in the environment. Dopaminergic (DA) projections from the ventral tegmental area (VTA) to the mPFC carry information, particularly about aversive outcomes, that may inform prefrontal computations. But the role of prefrontal DA in learning based on aversive outcomes remains poorly understood. Here, we used platform mediated avoidance (PMA) to study the role of mPFC DA in threat avoidance learning in mice. We show that activity in VTA-mPFC dopaminergic terminals is required for avoidance learning, but not for escape, conditioned fear, or to recall a previously learned avoidance strategy. mPFC DA is most dynamic in the early stages of learning, and encodes aversive outcomes, their omissions, and threat-induced behaviors. Computational models of PMA behavior and DA activity revealed that mPFC DA influences learning rates and encodes the predictive relationships between cues and adaptive behaviors. Taken together, these data indicate that mPFC DA is necessary to rapidly learn behaviors required to avoid signaled threats, but not for learning cue-threat associations.