Distinct ensembles in the prelimbic cortex track different measures of motivation for cocaine and water reinforcers.

The motivation to pursue drugs is a fundamental element of substance use. Different tasks assess motivation in the face of effort, punishment, or the absence of the drug, and recent studies have suggested that a shared latent variable may drive behavior across these tasks. The prelimbic cortex (PL) is implicated in these behaviors, but it is unknown if its role is driven by shared or distinct neural ensembles. We recorded PL activity using in vivo endoscopic calcium imaging in 32 male and female Sprague-Dawley rats as they completed cocaine or water self-administration, extinction, progressive ratio, and punished self-administration. We found that behavior across tasks was driven by a single latent variable in water, but not cocaine rats. We also found distinct neural populations that tracked reward pursuit. We found that one population of cost-sensitive neurons had significantly fewer neurons present during the progressive ratio task. A second population of reward-sensitive neurons had significantly fewer neurons present during the extinction task. Individual rats with more of these neurons present during the task had significantly higher levels of reward pursuit in the progressive ratio and extinction tasks, respectively. Furthermore, this relationship was true across cocaine and water rats, suggesting a general role in motivation independent of reward type. When we examined whether shared patterns of neural activity predicted shared patterns of behavior across the tasks, we found no relationships. Thus, our findings suggest that distinct facets of reward motivation are tracked by distinct ensembles in the PL, rather than a shared ensemble.