Dopamine enhances population coding of fear in prefrontal cortex.

Fear acquisition is a survival strategy enabling the prediction of potential threat on the basis of reliable environmental cues identified through associative learning. In this study we investigated the role of dorsomedial prefrontal cortex (dmPFC) - ventral tegmental area (VTA) coordination in fear acquisition. Despite the implication of a VTA-dmPFC circuit in fear acquisition, the mechanism by which the two structures interact and, most particularly, the manner in which dmPFC neuronal dynamics are impacted by DA remain largely unexplored. The present paper addresses this question by means of behavioral, optogenetic, and electrophysiological experiments. We first characterize the dynamics of VTA neurons and their relation with dmPFC during fear acquisition to then manipulate this dopaminergic inputs to dmPFC and address its role in fear memory expression and its dmPFC neuronal correlates. Our data first unravel that VTA neurons develop a conditioned stimulus coding activity through consecutive pairings with the unconditioned aversive stimulus and maintain this predictive activity overnight. Shutting down these VTA inputs to dmPFC resulted in a reduction in fear behavior and changes in population coding. These alteration were specific to spontaneous expression of fear and the population coding supporting that behavior. Our data show that dopamine role is to increase the accuracy of fear coding in dmPFC.