title: Deep brain stimulation of the ventral striatum increases BDNF in the fear extinction circuit.
abstract: Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) reduces the symptoms of treatment-resistant obsessive compulsive disorder (OCD), and improves response to extinction-based therapies. We recently reported that DBS-like stimulation of a rat homologue of VC/VS, the dorsal-VS, reduced conditioned fear and enhanced extinction memory (Rodriguez-Romaguera et al., 2012). In contrast, DBS of the ventral-VS had the opposite effects. To examine possible mechanisms of these effects, we assessed the effects of VS DBS on the expression of the neural activity marker Fos and brain-derived neurotrophic factor (BDNF), a key mediator of extinction plasticity in prefrontal-amygdala circuits. Consistent with decreased fear expression, DBS of dorsal-VS increased Fos expression in prelimbic and infralimbic prefrontal cortices and in the lateral division of the central nucleus of amygdala, an area that inhibits amygdala output. Consistent with improved extinction memory, we found that DBS of dorsal-VS, but not ventral-VS, increased neuronal BDNF expression in prelimbic and infralimbic prefrontal cortices. These rodent findings are consistent with the idea that clinical DBS of VC/VS may augment fear extinction through an increase in BDNF expression.
authors: Departments of Psychiatry and Anatomy and Neurobiology, University of Puerto Rico School of Medicine San Juan, Puerto Rico.
authors: Fabricio H
authors: FH
authors: Do-Monte
authors: Jose
authors: J
authors: Rodriguez-Romaguera
authors: Luis E
authors: LE
authors: Rosas-Vidal
authors: Gregory J
authors: GJ
authors: Quirk
keywords: Fos; amygdala; anxiety disorders; fear expression; high-frequency stimulation; obsessive compulsive disorder; prefrontal cortex
references: Curr Psychiatry Rep. 2011 Aug;13(4):274-82
references: 21505875
references: J Neurosci. 2004 May 19;24(20):4796-806
references: 15152040
references: Mol Pharmacol. 2007 Aug;72(2):235-7
references: 17522182
references: Psychiatr Clin North Am. 1992 Dec;15(4):743-58
references: 1461792
references: Neurochem Int. 2011 Jan;58(1):102-11
references: 21074587
references: Science. 2010 Feb 12;327(5967):863-6
references: 20075215
references: J Neurosci Methods. 1989 Sep;29(3):261-5
references: 2507830
references: J Neurosci. 2004 Jun 23;24(25):5704-10
references: 15215292
references: J Neurosci. 2005 Oct 19;25(42):9680-5
references: 16237172
references: Annu Rev Clin Psychol. 2011;7:229-43
references: 21443448
references: J Neurosci. 2012 Feb 22;32(8):2886-99
references: 22357871
references: Science. 1987 Jul 10;237(4811):192-7
references: 3037702
references: Neuroscience. 2002;115(2):455-62
references: 12421611
references: Learn Mem. 2006 Nov-Dec;13(6):728-33
references: 17142302
references: J Neurosci. 2013 Feb 27;33(9):3744-51
references: 23447586
references: J Clin Psychiatry. 1997;58 Suppl 13:9-13
references: 9402914
references: Mol Psychiatry. 2010 Jan;15(1):64-79
references: 18490925
references: Neuropharmacology. 2012 Jan;62(1):457-63
references: 21903111
references: Nat Neurosci. 2013 Apr;16(4):386-7
references: 23434914
references: J Neurosci. 2003 Sep 24;23(25):8800-7
references: 14507980
references: Nature. 2010 Nov 11;468(7321):277-82
references: 21068837
references: Science. 2010 Jun 4;328(5983):1288-90
references: 20522777
references: Learn Mem. 2007 Apr 06;14(4):268-76
references: 17522015
references: Neuropsychopharmacology. 2011 Jan;36(2):529-38
references: 20962768
references: Neuroscience. 1982 Mar;7(3):615-30
references: 7070669
references: J Neurosci. 2010 Apr 7;30(14):4990-8
references: 20371819
references: Synapse. 2004 Jan;51(1):32-58
references: 14579424
references: Nat Neurosci. 2010 Apr;13(4):489-94
references: 20208529
references: J Neurosci Methods. 1980 Dec;3(2):129-49
references: 6110810
references: Neurobiol Learn Mem. 2010 Mar;93(3):372-82
references: 19995614
references: J Neurosci Methods. 2011 Nov 15;202(2):113-8
references: 21565219
references: Learn Mem. 2009 Aug 25;16(9):520-9
references: 19706835
references: Neuroscience. 1991;44(1):15-33
references: 1722890
references: Neuropsychopharmacology. 2006 Feb;31(2):287-96
references: 16034442
references: Arch Gen Psychiatry. 2010 Oct;67(10):1061-8
references: 20921122
references: JAMA Psychiatry. 2013 Jun;70(6):608-18; quiz 554
references: 23740049
references: J Neurosci. 2009 Apr 22;29(16):5354-63
references: 19386932
references: J Neurosci. 2012 Feb 15;32(7):2410-21
references: 22396415
references: Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2675-80
references: 20133801
references: Learn Mem. 2009 Jul 24;16(8):486-93
references: 19633138
references: Behav Ther. 2009 Sep;40(3):251-9
references: 19647526
references: J Neurosci. 2011 Oct 26;31(43):15481-9
references: 22031894
references: Nat Neurosci. 2006 Jul;9(7):870-2
references: 16783370
references: Nature. 2008 Jul 31;454(7204):600-6
references: 18615015
references: J Neurosci. 2010 Jan 20;30(3):832-7
references: 20089891
references: Mol Brain. 2012 Oct 08;5:36
references: 23044043
references: Eur Psychiatry. 2012 Jul;27(5):386-90
references: 22153732
references: Psychiatry Res. 2012 Oct 30;199(3):195-200
references: 22494702
references: J Neurosci. 2005 Aug 10;25(32):7429-37
references: 16093394
references: J Neurochem. 2012 Dec;123(6):897-903
references: 23061486
references: J Affect Disord. 2010 Apr;122(1-2):174-8
references: 19664825
references: Genes Brain Behav. 2012 Jul;11(5):503-12
references: 22530815
references: Proc Natl Acad Sci U S A. 2012 May 29;109(22):8764-9
references: 22586125
references: J Psychiatr Res. 2013 Jan;47(1):33-41
references: 22999486
references: Eur J Neurosci. 1992;4(6):459-471
references: 12106332