Prefrontal Deep Projection Neurons Enable Cognitive Flexibility Via Persistent Feedback Monitoring

Abstract

Cognitive flexibility, the ability to alter one’s strategy in light of changing stimulus-response-reward relationships, is critical for acquiring and updating learned behavior by trial and error. Successful performance of attentional set-shifting, a test of cognitive flexibility, has been shown to critically involve the prefrontal cortex (PFC). It is unclear, however, whether PFC neurons support set-shifting behavior by guiding action selection or by monitoring feedback from completed actions. Using optogenetics and 2-photon calcium imaging, we demonstrate that PFC activity critically encodes trial feedback information, rather than guiding action selection, to enable set-shifting. Moreover, we find that, in two distinct PFC projection populations, representations of trial feedback form a topological gradient, with cells more strongly selective for feedback information located further from the pial surface, regardless of their projection targets. Together, these findings indicate that deep PFC projection neurons enable set-shifting through monitoring of behavioral feedback.