Dissociable Roles of Prelimbic and Orbitofrontal Cortices in the Flexible Use of Model-Based Associations

Our environment is complex and to navigate it effectively, we organize conceptual and spatial information into a coherent cognitive map. This allows us to be flexible and make novel inferences to maximize procurement of the things we need and minimize negative events. Decision making based on such cognitive maps is generally described as model-based behavior, which refers to an ability to simulate likely paths to reward via a transitional structure of the task. We have previously modelled how different prefrontal regions contribute to deploying cognitive maps to facilitate flexible behavior. We hypothesized that the prelimbic region- as analogous to the dorsolateral prefrontal cortex in humans- is necessary to upload the current relevant map, while orbitofrontal cortex tracks position within the map as subjects traverse it. To test this, we developed a sequential biconditional discrimination task allowing optical inhibition during either map upload or position tracking in male and female rats. We show this task engenders a detailed model-based cognitive map, fostering the ability to make novel inferences. Consistent with our framework, optical inhibition of the orbitofrontal cortex disrupts rats' ability to track their current position in the map. In contrast, optical inhibition of the prelimbic cortex reduces performance when rats must upload the current map. While rats without prelimbic activity during map upload still show discriminative performance, their discrimination is uncoupled from that seen during training, suggesting a compensatory mechanism. Together, these data reveal dissociable contributions of the orbitofrontal and prelimbic cortices to cognitive map deployment. Significance Statement Our ability to behave appropriately in new or unfamiliar situations depends on what we learn from experience. To navigate complex environments, we develop cognitive maps that comprise mental frameworks organising learned information into coherent schemas. These allow us to choose between courses of action in different contexts and to draw new inferences in entirely novel situations. The ability to form and use such maps is disrupted in psychological disorders including addiction and schizophrenia. Our work reveals new information on how the brain constructs and deploys cognitive maps, bringing us closer to understanding the cognitive disruptions that underlie these disorders.