484. MAPPING NEURONAL ENSEMBLE ACTIVITY IN THE MOUSE PREFRONTAL CORTEX DURING MOTIVATIONAL CONTROL OF BEHAVIOR FOLLOWING KETAMINE TREATMENT

Abstract Background Disrupted motivational control of behavior and impairments in effort-based decision making are central to depression and mood disorders. Human imaging studies in individuals with clinical depression have shown dysfunctional activity in key brain regions such as the prefrontal cortex (PFC) and the lateral habenula (LHb). Yet, the mechanistic nature of dysfunction in these regions, how it might be modulated by rapid-acting antidepressants like ketamine, and how these correlate to regulation of motivated behaviors, remains elusive. Aims & Objectives Here, we sought to measure how PFC neurons that project to the LHb govern motivated behavior and effort-based decision making. Method We used single-photon calcium imaging of PFC-LHb projection neurons while mice performed touchscreen-based tests for motivational control of behavior. We assessed the effect of ketamine treatment on both neural activity and behavioral measures. Results We found PFC-LHb projection neurons did not exhibit uniform population activity; rather, their activity increased or decreased depending on the behavior. Consistent with this, we identified heterogenous ensembles with selective activity patterns based on the specific behavioral response. Importantly, we also observed that neurons retain an encoding identity across days, and when task demands change. Discussion & Conclusions Our data suggest PFC-LHb projection neurons track and update information about reward-based outcomes to inform behavioral actions. Our findings contribute to better understanding the neural disturbances in prefrontal circuitry that underlie aberrant motivational states in complex mental health conditions like depression and mood disorders, and how these processes might be regulated by emerging rapid-acting antidepressants.