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PMID: 25601229 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Enhancement of fear extinction with deep brain stimulation: evidence for medial orbitofrontal involvement.

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology ·Vol. 40 ·No. 7 ·2015-06-00 ·Pages 1726-33

Rodriguez-Romaguera J, Do-Monte FH, Tanimura Y, Quirk GJ, Haber SN

Abstract

Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) reduces anxiety, fear, and compulsive symptoms in patients suffering from refractory obsessive-compulsive disorder. In a rodent model, DBS-like high-frequency stimulation of VS can either enhance or impair extinction of conditioned fear, depending on the location of electrodes within VS (dorsal vs ventral). As striatal DBS activates fibers descending from the cortex, we reasoned that the differing effects on extinction may reflect differences in cortical sources of fibers passing through dorsal-VS and ventral-VS. In agreement with prior anatomical studies, we found that infralimbic (IL) and anterior insular (AI) cortices project densely through ventral-VS, the site where DBS impaired extinction. Contrary to IL and AI, we found that medial orbitofrontal cortex (mOFC) projects densely through dorsal-VS, the site where DBS enhanced extinction. Furthermore, pharmacological inactivation of mOFC reduced conditioned fear and DBS of dorsal-VS-induced plasticity (pERK) in mOFC neurons. Our results support the idea that VS DBS modulates fear extinction by stimulating specific fibers descending from mOFC and prefrontal cortices.

MeSH Terms
Acoustic Stimulation Analysis of Variance Animals Conditioning, Operant/drug effects,physiology Deep Brain Stimulation Extinction, Psychological/drug effects,physiology Extracellular Signal-Regulated MAP Kinases/metabolism Fear/physiology GABA-A Receptor Agonists/pharmacology Male Muscimol/pharmacology Prefrontal Cortex/physiology Rats Rats, Sprague-Dawley Wheat Germ Agglutinins/metabolism
Chemicals
GABA-A Receptor Agonists Wheat Germ Agglutinins Muscimol Extracellular Signal-Regulated MAP Kinases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Rodriguez-Romaguera Jose
1] Department of Psychiatry, University of Puerto Rico-School of Medicine, San Juan, PR, Puerto Rico [2] Department of Anatomy and Neurobiology, University of Puerto Rico-School of Medicine, San Juan, PR, Puerto Rico.
Do-Monte Fabricio H
1] Department of Psychiatry, University of Puerto Rico-School of Medicine, San Juan, PR, Puerto Rico [2] Department of Anatomy and Neurobiology, University of Puerto Rico-School of Medicine, San Juan, PR, Puerto Rico.
Tanimura Yoko
Department of Pharmacology and Physiology, University of Rochester School of Medicine, Rochester, NY, USA.
Quirk Gregory J
1] Department of Psychiatry, University of Puerto Rico-School of Medicine, San Juan, PR, Puerto Rico [2] Department of Anatomy and Neurobiology, University of Puerto Rico-School of Medicine, San Juan, PR, Puerto Rico.
Haber Suzanne N
Department of Pharmacology and Physiology, University of Rochester School of Medicine, Rochester, NY, USA.
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Article Info
Journal
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
Abbr.
Neuropsychopharmacology
ISSN
1740-634X
DOI
10.1038/npp.2015.20
Published
2015-06-00
Epub
2015-00-20
Pages
1726-33
Language
English
Region
England
NLM ID
8904907
PMCID
PMC4915256
Subset
IM
Grants
NIMH NIH HHS · P50 MH086400 · United States
NIMH NIH HHS · P50 MH106435 · United States
NIMH NIH HHS · R37 MH058883 · United States
NIMH NIH HHS · R01 MH081975 · United States
NIMH NIH HHS · R36 MH105039 · United States
External Links
PubMed source DOI: 10.1038/npp.2015.20 PMC Full Text View journal details
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