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 #
5P50MH086400-02
Application #
8076852
Study Section
Special Emphasis Panel (ZMH1)
Project Start
2010-06-01
Project End
2014-05-31
Budget Start
2010-06-01
Budget End
2011-05-31
Support Year
2
Fiscal Year
2010
Total Cost
$297,209
Indirect Cost
Name
University of Rochester
Department
Type
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627
Martínez-Rivera, Freddyson J; Barreto-Estrada, Jennifer L (2018) Reply to: Does High-Frequency Deep Brain Stimulation in Dorsal Regions of the Ventral Striatum Impair Extinction of Morphine-Induced Place Preference? Biol Psychiatry 83:e21
Patel, Shaun R; Herrington, Todd M; Sheth, Sameer A et al. (2018) Intermittent subthalamic nucleus deep brain stimulation induces risk-aversive behavior in human subjects. Elife 7:
Martinez-Rubio, Clarissa; Paulk, Angelique C; McDonald, Eric J et al. (2018) Multimodal Encoding of Novelty, Reward, and Learning in the Primate Nucleus Basalis of Meynert. J Neurosci 38:1942-1958
Do-Monte, Fabricio H; Minier-Toribio, Angélica; Quiñones-Laracuente, Kelvin et al. (2017) Thalamic Regulation of Sucrose Seeking during Unexpected Reward Omission. Neuron 94:388-400.e4
Alexandra Kredlow, M; Pineles, Suzanne L; Inslicht, Sabra S et al. (2017) Assessment of skin conductance in African American and Non-African American participants in studies of conditioned fear. Psychophysiology 54:1741-1754
Heilbronner, Sarah R; Rodriguez-Romaguera, Jose; Quirk, Gregory J et al. (2016) Circuit-Based Corticostriatal Homologies Between Rat and Primate. Biol Psychiatry 80:509-21
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
Do Monte, F H; Quirk, G J; Li, B et al. (2016) Retrieving fear memories, as time goes by…. Mol Psychiatry 21:1027-36
Martínez-Rivera, Freddyson J; Rodriguez-Romaguera, Jose; Lloret-Torres, Mario E et al. (2016) Bidirectional Modulation of Extinction of Drug Seeking by Deep Brain Stimulation of the Ventral Striatum. Biol Psychiatry 80:682-690
Do-Monte, Fabricio H; Manzano-Nieves, Gabriela; Quiñones-Laracuente, Kelvin et al. (2015) Revisiting the role of infralimbic cortex in fear extinction with optogenetics. J Neurosci 35:3607-15

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