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.
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.
|Do Monte, F H; Quirk, G J; Li, B et al. (2016) Retrieving fear memories, as time goes byâ€¦. Mol Psychiatry 21:1027-36|
|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|
|Neske, Garrett T; Patrick, Saundra L; Connors, Barry W (2015) Contributions of diverse excitatory and inhibitory neurons to recurrent network activity in cerebral cortex. J Neurosci 35:1089-105|
|Ahmari, Susanne E; Dougherty, Darin D (2015) DISSECTING OCD CIRCUITS: FROM ANIMAL MODELS TO TARGETED TREATMENTS. Depress Anxiety 32:550-62|
|Sierra-Mercado, Demetrio; Deckersbach, Thilo; Arulpragasam, Amanda R et al. (2015) Decision making in avoidance-reward conflict: a paradigm for non-human primates and humans. Brain Struct Funct 220:2509-17|
|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; QuiÃ±ones-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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