The orbitofrontal cortex regulates outcome-based decision-making via the lateral striatum

• Type of Material: Article
• Authors: Shannon L. Gourley, Emory University; Anastasia Olevska, Yale University; Kelsey S. Zimmermann, Emory University; Kerry Ressler, Emory University; Ralph J. DiLeone, Yale University; Jane R. Taylor, Yale University
• Language: English
• Date: 2013-08
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd
• Final Published Version (URL): http://onlinelibrary.wiley.com/doi/10.1111/ejn.12239/abstract
• Title of Journal or Parent Work: European Journal of Neuroscience
• ISSN: 0953-816X
• Volume: 38
• Issue: 3
• Grant/Funding Information: This work was supported by DA011717, UL1-DE19586 and the Roadmap for Medical Research/Common Fund, AA017537; the Connecticut Mental Health Center; and Children’s Healthcare of Atlanta. The components of this project performed at the Yerkes National Primate Research Center were also funded by the National Center for Research Resources P51RR165 (currently Office of Research Infrastructure Programs/OD P51OD11132).
• Keywords: outcome; addiction; contingency; habit; orbital; action
• Research Categories: Biology, Neuroscience

Abstract

The orbitofrontal cortex (oPFC) sends substantial projections to the ventrolateral striatum and aspects of the nucleus accumbens that are—functionally—poorly understood. This is despite probable cortico-striatal involvement in multiple diseases such as addiction and obsessive-compulsive disorder. Here we surgically disconnected the oPFC from the ventrolateral striatum using unilateral asymmetric lesions in mice and classified instrumental decision-making strategies. Mice with symmetric lesions that spared one oPFC-striatal network served as controls. As a complementary approach, we selectively knocked down Brain-derived neurotrophic factor (Bdnf) bilaterally in the oPFC and ascertained behavioral and neurobiological consequences within the downstream striatum. oPFC-striatal disconnection and oPFC Bdnf knockdown blocked sensitivity to outcome-predictive relationships in both food-reinforced and cocaine-associated settings. Bdnf knockdown simultaneously regulated striatal BDNF expression, and striatal c-Fos predicted sensitivity to action-outcome associative contingencies. Prior evidence strongly implicates the dorsolateral striatum in stimulus-response habit formation. Our findings thus provide novel evidence for functional compartmentalization within the lateral striatum, with the dorsal compartment subserving classical stimulus-response habit systems and a ventral compartment coordinating outcome-based decision-making via oPFC interactions. This compartmentalization may apply to both ‘natural’—as in the case of food-reinforced behavior—and ‘pathological’—as in the case of cocaine-seeking—contexts.