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Eur J Neurosci. 2013 Aug;38(3):2382-8. doi: 10.1111/ejn.12239. Epub 2013 May 8.

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

Author information

1
Department of Pediatrics, Yerkes National Primate Research Center, Emory University, 954 Gatewood Drive NE, Atlanta, GA 30322, USA. shannon.l.gourley@emory.edu

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. Previous evidence strongly implicates the dorsolateral striatum in stimulus-response habit formation. Our findings thus provide novel evidence for functional compartmentalisation 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 compartmentalisation may apply to both 'natural', as in the case of food-reinforced behavior, and 'pathological', as in the case of cocaine-seeking, contexts.

KEYWORDS:

action; addiction; contingency degradation; habit; mouse; orbital

PMID:
23651226
PMCID:
PMC3864662
DOI:
10.1111/ejn.12239
[Indexed for MEDLINE]
Free PMC Article
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