This project will focus on studying the circuitry involved in avoidance and reward behavior in awake-behaving primates. Primates are a critical link in this project because they are intelligent and can be trained to perform complex tasks that mimic human behaviors, the homology between areas of interest is fairiy close between primates and humans, and there is a considerable anatomic information regarding areas involved in mediating reward and avoidance, and invoked in obsessive-compulsive disorder (OCD). These areas include the ventro-medial prefrontal cortex (vmPFC), the orbitofrontal cortex (OFC), the anterior dorsal cingulate cortex (dACC) and the ventral striatum (VS). There is considerable data regarding the circuitry of fear extinction in rodents. In particular, the infralimic (IL) and pre-limbic (PL) areas appear to have a reciprocal role in the mediating fear extinction (Quirk). Although the exact homology is not clear, a reasonable hypothesis is that IL corresponds to the vmPFC and that area PL corresponds to the dACC. In contrast, there has been relatively little work studying these areas in primates. The overarching goal of this project is to bridge the gap between rodents and primates, which will then provide an important framework for the rational development of DBS strategies aimed at treating human disorders.

Public Health Relevance

Obsessive Compulsive Disorder (OCD) is a chronic psychiatric illness that affects 2-3% of the woridwide population. This is disease is in the top ten dehabilitating diseases. This study will examine the neural network and mechanisms that underiie behaviors associated with OCD. These behaviors not limited to OCD, but are associated with a range of affective and addictive disorders. The collective proposed studies will generate new hypotheses of how dysfunctions within these brain networks are expressed across diseases and provide insight into the mechanisms underiying normal behavioral responses.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center (P50)
Project #
5P50MH086400-04
Application #
8375307
Study Section
Special Emphasis Panel (ZMH1-ERB-F)
Project Start
Project End
Budget Start
2012-06-01
Budget End
2013-05-31
Support Year
4
Fiscal Year
2012
Total Cost
$271,310
Indirect Cost
Name
University of Rochester
Department
Type
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627
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Rodriguez-Romaguera, Jose; Greenberg, Benjamin D; Rasmussen, Steven A et al. (2016) An Avoidance-Based Rodent Model of Exposure With Response Prevention Therapy for Obsessive-Compulsive Disorder. Biol Psychiatry 80:534-40
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Rodriguez-Romaguera, Jose; Do-Monte, Fabricio H; Tanimura, Yoko et al. (2015) Enhancement of fear extinction with deep brain stimulation: evidence for medial orbitofrontal involvement. Neuropsychopharmacology 40:1726-33
Rodriguez-Romaguera, Jose; Greenberg, Benjamin D; Haber, Suzanne N et al. (2015) A Cross Species Approach to Understanding DBS Modulation of Fear. Brain Stimul 8:986-8
Do-Monte, Fabricio H; Quiñones-Laracuente, Kelvin; Quirk, Gregory J (2015) A temporal shift in the circuits mediating retrieval of fear memory. Nature 519:460-3
Sierra-Mercado, Demetrio; McAllister, Lauren M; Lee, Christopher C H et al. (2015) Controlled cortical impact before or after fear conditioning does not affect fear extinction in mice. Brain Res 1606:133-41
McLaughlin, N C R; Strong, D; Abrantes, A et al. (2015) Extinction retention and fear renewal in a lifetime obsessive-compulsive disorder sample. Behav Brain Res 280:72-7

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