RT Journal Article
SR Electronic
T1 Prefrontal deep projection neurons enable cognitive flexibility via persistent feedback monitoring
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 828590
DO 10.1101/828590
A1 Spellman, T
A1 Svei, M
A1 Liston, C
YR 2019
UL http://biorxiv.org/content/early/2019/11/04/828590.1.abstract
AB Cognitive flexibility, the ability to alter one’s strategy in light of changing stimulus-response-reward relationships, is a critical tool for acquiring and updating learned behavior. In order to adapt to novel, uncertain, or dynamic contexts, it is often necessary to abandon previously successful rules and explore new rules, based on trial and error. One behavioral model of cognitive flexibility, set-shifting, entails ignoring a previously relevant stimulus feature in favor of a newly relevant feature. Successful performance on these tasks has been shown to involve the prefrontal cortex (PFC), and impairments in set-shifting are associated with multiple psychiatric disorders. In spite of the translational importance of this behavior, it remains unclear which cell types within PFC are responsible for conveying information critical to set-shifting to downstream regions. To address this question, we developed a novel task for head-fixed mice to test the role of two major PFC projections, the cortico-striatal and cortico-thalamic pathways, in set-shifting behavior. Using optogenetics and 2-photon calcium imaging, we found that these cell types robustly and persistently encoded feedback from the outcomes of recent trials, and that the activity of both cell types during the inter-trial interval was critical to successfully switching between task rules. Moreover, we found that both populations displayed a topological gradient, with neurons located further from the pial surface representing more task-critical information. Together, these findings suggest that deep PFC projection neurons enable set-shifting through monitoring of feedback from recent trials.