Divergent reward cue representations in the prefrontal cortex drive reward motivation in adolescence and adulthood

Alterations in motivation and reward-seeking are a transdiagnostic feature of numerous psychiatric disorders that commonly emerge in adolescence, including depression, obsessive- compulsive disorder, and attention deficit hyperactivity disorder. During adolescence, reward motivation is naturally heightened, compared to adulthood, but the underlying mechanisms are not well understood. The medial prefrontal cortex (mPFC) is a late developing brain region that regulates reward learning and motivation and is still maturing in adolescence. The mPFC modulates reward-motivated behaviors in adults, and has been hypothesized to be responsible for adolescents’ inability to suppress reward-seeking and impulsive behaviors. Using 2-photon imaging of the mPFC and an active reward task, we demonstrate that both the adult and adolescent mPFC encode reward-predictive cues, with distinct neuronal populations encoding rewarded and unrewarded cues. In adolescence the mPFC is hyper-responsive to reward cues and recruits a larger population of neurons to encode reward predictive cues. Furthermore, in the adolescent mPFC, representations of unrewarded cues are attenuated, compared to the adult mPFC, which may tip the balance of action toward reward-seeking. Differences in neuronal responses to rewarded and unrewarded cues were observed in both GABAergic and glutamatergic neurons, with GABAergic inhibition causing disparate effects in adolescents compared to adults. Together our findings identify differences in the functional properties of mPFC microcircuits in adolescents that may underlie differences in reward-seeking behavior and the ability to adaptively suppress reward seeking.