Dissociable cortical-hippocampal dopamine dynamics support memory-guided behavior.

Flexible behavior depends on neural mechanisms that integrate memory with ongoing motivational demands. Studies have revealed dopamine (DA) to have an essential role in mediating memory, behavioral flexibility, and decision-making, yet the dopaminergic contributions within prefrontal-hippocampal circuits remain poorly defined. To address this, we simultaneously monitored DA release and population calcium activity in the prelimbic cortex (PL) and ventral CA1 (vCA1) using genetically encoded sensors during threat learning, reward learning, and an approach-avoidance conflict task. Both regions exhibited distinct dopaminergic and neural responses to the cues that predicted shock or reward and to the respective behaviors that each cue elicited. DA signals in the PL, but not vCA1, tracked the latency of avoidance behavior on a trial-by-trial scale and emerged rapidly as animals acquired the threat association. By contrast, vCA1 DA showed modulation by latency to avoid at an individual level. Together, PL and vCA1 DA reorganized when animals were forced to choose between approach and avoidance. This reorganization reflects early during the trial whether animals will seek reward and later whether the animals will stay on the platform during the final epochs of conflict trials. These results demonstrate complementary dopaminergic functions in PL and vCA1 and reveal how their dynamics reshape during memory-guided actions under competing motivational pressures.