Prefrontal encoding of an internal model for emotional inference

A key function of brain systems mediating emotion is to learn to anticipate unpleasant experiences based on predictive sensory cues in the environment. While organisms readily associate sensory stimuli with aversive outcomes, higher-order forms of emotional learning and memory require inference to extrapolate the circumstances surrounding directly experienced aversive events to other indirectly related contexts and sensory patterns which weren’t a part of the original experience. To achieve this type of learning requires internal models of emotion which flexibly track directly experienced and inferred aversive associations. While the brain mechanisms of simple forms of aversive learning have been well studied in areas such as the amygdala, whether and how the brain represents internal models of emotionally relevant associations is not known. Here we report that neurons in the rodent dorsomedial prefrontal cortex (dmPFC) encode an internal model of emotion by linking sensory stimuli in the environment with aversive events, whether they were directly or indirectly associated with that experience. These representations are flexible, and updating the behavioral significance of individual features of the association selectively modifies corresponding dmPFC representations. While dmPFC population activity encodes all salient associations, dmPFC neurons projecting to the amygdala specifically represent and are required to express inferred associations. Together, these findings reveal how internal models of emotion are encoded in dmPFC to regulate subcortical systems for recall of inferred emotional memories.