title: The orbitofrontal cortex regulates outcome-based decision-making via the lateral striatum.
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.
authors: Department of Pediatrics, Yerkes National Primate Research Center, Emory University, 954 Gatewood Drive NE, Atlanta, GA 30322, USA. shannon.l.gourley@emory.edu
authors: Shannon L
authors: SL
authors: Gourley
authors: Anastasia
authors: A
authors: Olevska
authors: Kelsey S
authors: KS
authors: Zimmermann
authors: Kerry J
authors: KJ
authors: Ressler
authors: Ralph J
authors: RJ
authors: Dileone
authors: Jane R
authors: JR
authors: Taylor
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003216:Conditioning, Operant / Q000502:physiology; D003342:Corpus Striatum / Q000502:physiology*; D003657:Decision Making / Q000502:physiology*; D005625:Frontal Lobe / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000502:physiology
chemical_list: D019208:Brain-Derived Neurotrophic Factor
keywords: action; addiction; contingency degradation; habit; mouse; orbital
references: Eur J Neurosci. 2005 Jul;22(2):513-23
references: 16045504
references: J Comp Neurol. 1992 Feb 15;316(3):314-47
references: 1577988
references: Nat Rev Neurosci. 2009 Dec;10(12):885-92
references: 19904278
references: Neuron. 2009 Apr 30;62(2):269-80
references: 19409271
references: Neurosci Lett. 2008 Feb 13;432(1):40-5
references: 18248891
references: Eur J Neurosci. 2010 Nov;32(10):1726-34
references: 21044173
references: Science. 1995 Oct 27;270(5236):593-8
references: 7570017
references: J Neurosci. 2003 Jan 15;23(2):666-75
references: 12533626
references: Behav Brain Res. 2003 Nov 30;146(1-2):145-57
references: 14643467
references: Psychopharmacology (Berl). 1999 Oct;146(4):373-90
references: 10550488
references: Eur J Neurosci. 2008 Oct;28(8):1437-48
references: 18793321
references: Cell. 2003 Jan 24;112(2):257-69
references: 12553913
references: Eur J Neurosci. 2004 Jan;19(1):181-9
references: 14750976
references: Mol Endocrinol. 2001 Oct;15(10):1748-57
references: 11579207
references: Cold Spring Harb Perspect Biol. 2010 Apr;2(4):a001842
references: 20452946
references: Nat Neurosci. 2009 Mar;12(3):333-41
references: 19198605
references: J Neurosci. 2012 Feb 15;32(7):2314-23
references: 22396406
references: Proc Natl Acad Sci U S A. 2012 Dec 11;109(50):20714-9
references: 23185000
references: Exp Brain Res. 1996 Sep;111(2):215-32
references: 8891652
references: Cereb Cortex. 2003 Apr;13(4):400-8
references: 12631569
references: Trends Cogn Sci. 2007 Apr;11(4):168-76
references: 17337237
references: Behav Brain Res. 2013 Apr 15;243:171-5
references: 23327740
references: J Neurosci. 2008 Oct 29;28(44):11124-30
references: 18971455
references: J Neurophysiol. 2009 Jul;102(1):475-89
references: 19439679
references: Neuroscience. 2012 Jun 14;212:1-18
references: 22542678
references: Learn Mem. 2009 Nov 19;16(12):756-60
references: 19926781
references: Neuropsychopharmacology. 2010 Jan;35(1):48-69
references: 19776734
references: J Neurosci. 2007 May 2;27(18):4819-25
references: 17475789
references: Behav Brain Res. 2006 Jan 30;166(2):189-96
references: 16153716
references: Nat Neurosci. 2012 Jan 22;15(3):358-66
references: 22267164
references: J Comp Neurol. 2003 Dec 15;467(3):271-92
references: 14608594
references: J Exp Anal Behav. 1980 Nov;34(3):297-304
references: 16812191
references: Neuron. 2010 May 13;66(3):449-60
references: 20471357
references: Neuropharmacology. 1998 Apr-May;37(4-5):407-19
references: 9704982
references: Brain Res Mol Brain Res. 2005 Oct 31;140(1-2):86-90
references: 16109452
references: PLoS One. 2011;6(10):e26065
references: 22022509
references: Nat Neurosci. 2005 Nov;8(11):1481-9
references: 16251991
references: Synapse. 2000 Sep 15;37(4):252-61
references: 10891862
references: Biol Psychiatry. 2008 Nov 15;64(10):884-90
references: 18675955
references: Transl Psychiatry. 2012 Dec 18;2:e205
references: 23250006