Insular and Ventrolateral Orbitofrontal Cortices Differentially Contribute to Goal-Directed Behavior in Rodents

: The medial prefrontal cortex (mPFC) has long been considered a critical site in action control. However, recent evidence indicates that the contribution of cortical areas to goal-directed behavior likely extends beyond mPFC. Here, we examine the function of both insular (IC) and ventrolateral orbitofrontal (vlOFC) cortices in action-dependent learning. We used chemogenetics to study the consequences of IC or vlOFC inhibition on acquisition and performance of instrumental actions using the outcome devaluation task. Rats first learned to associate actions with desirable outcomes. Then, one of these outcomes was devalued and we assessed the rats' choice between the 2 actions. Typically, rats will bias their selection towards the action that delivers the still valued outcome. We show that chemogenetic-induced inhibition of IC during choice abolishes goal-directed control whereas inhibition during instrumental acquisition is without effect. IC is therefore necessary for action selection based on current outcome value. By contrast, vlOFC inhibition during acquisition or the choice test impaired goal-directed behavior but only following a shift in the instrumental contingencies. Our results provide clear evidence that vlOFC plays a critical role in action-dependent learning, which challenges the popular idea that this region of OFC is exclusively involved in stimulus-dependent behaviors.