Dopaminergic projections to the prefrontal cortex are critical for rapid threat avoidance learning

To survive, animals must rapidly learn to avoid predictable threats. Such learning depends on detecting reliable cue-outcome relationships that efficiently drive behavioral adaptations. The medial prefrontal cortex (mPFC) integrates learned information about the environment to guide adaptive behaviors1,2,3,4,5,6,7 and is critical for threat avoidance.8,9,10,11,12,13,14 However, most studies focused on well-learned threat avoidance strategies, and the specific inputs that signal avoidability and drive rapid avoidance learning remain poorly understood. Dopamine (DA) inputs from the ventral tegmental area (VTA) potently modulate prefrontal function and are preferentially engaged by aversive stimuli.15,16,17,18,19,20,21 Pharmacological blockade, DA depletion, and microdialysis experiments implicated DA in threat avoidance22,23,24,25 but lacked the spatiotemporal resolution required to define the timing of mPFC DA signals during avoidance learning. We used high-resolution tools to dissect the role of the VTA-mPFC DA circuit in rapid avoidance learning. Optogenetic suppression of VTA DA terminals in mPFC selectively slowed learning of a cued avoidance response without affecting cue-shock association learning, reactive escape behaviors, or expression of previously learned avoidance. Using a fluorescent DA sensor, we observed rapid, event-locked DA activity that emerged transiently during learning initiation. Increased DA encoded aversive outcomes and their predictive cues, while decreased DA encoded their omission and predicted how quickly mice learned to avoid. In yoked mice lacking control over shock omission, these dynamics were largely absent. Together, these findings demonstrate that the VTA-mPFC DA circuit is necessary for rapid acquisition of proactive avoidance behaviors and reveal transient event-related DA signals underlying this form of learning.