A shared ensemble in the prelimbic cortex links impulsivity and anxiety-like behavior

Mental health disorders often share overlapping behavioral and neural features, yet it remains unclear why these relationships emerge or whether they reflect common underlying neural processes. To explore this, we recorded prelimbic (PL) activity using endoscopic calcium imaging as rats completed a battery of tasks assessing impulsivity, distress tolerance, anxiety-like behavior, incentive salience (Pavlovian conditioned approach), and sensation-seeking in a novel environment (locomotor activity). By collecting neural and behavioral measures across all tasks within each animal, we were able to investigate whether PL activity tracked processes that were either unique to individual behaviors, shared across multiple behaviors, or both. We found that PL activity was significantly predictive of each of the behaviors except locomotor activity. Subsequent analyses revealed shared behavioral structure across tasks, with one latent dimension reflecting high impulsivity and low anxiety-like behavior. Individual variability across this particular dimension was strongly predicted by a neural structure comprising shared PL activity across four of the behaviors. Furthermore, this relationship was driven by a subset of PL neurons that shared patterns of activity across multiple tasks, forming a shared neural ensemble. Importantly, animals with a greater tendency to share neural ensembles exhibited a stronger link between high impulsivity and low anxiety-like behavior. These findings suggest that a small, shared ensemble of PL neurons tracked activity across multiple clinically-relevant behaviors to predict an approach/avoidance phenotype characterized by high impulsivity and low anxiety. This points toward a targetable neural population that may help explain why diverse psychiatric symptoms often co-occur within individuals.