Rationale During value-based decision-making, organisms make choices on the basis of reward expectations, which have been formed during prior action-outcome learning. Although it is known that neuronal manipulations of different subregions of the rat prefrontal cortex (PFC) have qualitatively different effects on behavioral tasks involving value-based decision-making, it is unclear how these regions contribute to the underlying component processes. Objectives Assessing how different regions of the rodent PFC contribute to component processes of value-based decisionmaking behavior, including reward (or positive feedback) learning, punishment (or negative feedback) learning, response persistence, and exploration versus exploitation. Methods We performed behavioral modeling of data of rats in a probabilistic reversal learning task after pharmacological inactivation of five PFC subregions, to assess how inactivation of these different regions affected the structure of responding of animals in the task. Results Our results show reductions in reward and punishment learning after PFC subregion inactivation. The prelimbic, infralimbic, lateral orbital, and medial orbital PFC particularly contributed to punishment learning, and the prelimbic and lateral orbital PFC to reward learning. In addition, response persistence depended on the infralimbic and medial orbital PFC. As a result, pharmacological inactivation of the infralimbic and lateral orbitofrontal cortex reduced the number of reversals achieved, whereas inactivation of the prelimbic and medial orbitofrontal cortex decreased the number of rewards obtained. Finally, using simulated data, we explain discrepancies with a previous study and demonstrate complex, interacting relationships between conventional measures of probabilistic reversal learning performance, such as win-stay/lose-switch behavior, and component processes of value-based decision-making. Conclusions Together, our data suggest that distinct components of value-based learning and decision-making are generated in medial and orbital PFC regions, displaying functional specialization and overlap, with a prominent role of large parts of the PFC in negative feedback processing.

Being able to limit the pursuit of reward to prevent negative consequences is an important expression of behavioral inhibition. Everyday examples of an inability to exert such control over behavior are the overconsumption of food and drugs of abuse, which are important factors in the development of obesity and addiction, respectively. Here, we use a behavioral task that assesses the ability of male rats to exert behavioral restraint at the mere sight of palatable food during the presentation of an audiovisual threat cue to investigate the corticolimbic underpinnings of behavioral inhibition. We demonstrate a prominent role for the medial prefrontal cortex in the exertion of control over behavior under threat of punishment. Moreover, task engagement relies on function of the ventral striatum, whereas the basolateral amygdala mediates processing of the threat cue. Together, these data show that inhibition of reward pursuit requires the coordinated action of a network of corticolimbic structures.There is a need for translational models that allow to dissect mechanisms underlying the processes involved in controlling behavior. In this study, we present a novel behavioral task that assesses the ability of rats to exert behavioral restraint over the consumption of a visually present sucrose pellet during the presentation of an audiovisual threat cue. This task requires relatively little behavioral training and it discerns distinct behavioral impairments, including a failure to retrieve stimulus value, a reduced task engagement, and compromised inhibition of behavior. Using pharmacological inactivations of different regions of the corticolimbic system of the rat, we demonstrate dissociable roles for the prefrontal cortex, amygdala, and striatum in inhibition of reward pursuit under threat of punishment.