Kerry J. Ressler, MD, PhD is an assistant professor in the Department of Psychiatry and Behavioral Sciences at Emory University. As a psychiatrist trained in molecular biology and neurobiology, his driving interest has been the understanding of neural systems that undedie behavior and emotion. Following residency, he started a laboratory at Emory's Yerkes Research Center in the Center for Behavioral Neuroscience to focus on molecular mechanisms of amygdala functioning. Dr. Ressler is now in an optimal position to complete his training in behavioral neuroscience with Dr. Michael Davis, a leader in the field, as a mentor. The Mentored Research Scientist Development Award is perfectly suited to assist in his career development, so that he may become a productive researcher with full training in molecular and behavioral neurobiology that is also informed by his psychiatry training and experience. Dr. Ressler spends approximately 15% of his time directing a clinic specializing in the treatment of Post-traumatic Stress Disorder (PTSD), a disorder of fear dyregulation. Treatment of PTSD, as well as phobia, panic disorder, and other anxiety disorders depends upon the teaming process of extinction -- the primary mechanism by which learned fear is reduced. It is now known that extinction is an active process of inhibitory learning that involves synaptic plasticity and that may occur within the amygdala and the infralimbic prefrontal cortex, an area that modulates amygdata activity.
The specific aims of this proposal will investigate the role of calcium dependent synaptic plasticity in mediating extinction learning in the amygdala and prefrontal cortex. It is thought that calcium entry through the NMDA receptor (NMDAR) and the L-type voltage gated calcium channel (VGCC) may have different functions during the consolidation of extinction. These experiments will first identify synaptic plasticity genes involved in the consolidation of extinction. This will be followed by behavioral and gene expression analyses of extinction following facilitation or inhibition of extinction with NMDAR and VGCC agonists and antagonists. Finally, gene expression and cell-type specificity will be examined by using viral mediated gene transfer of dominant negative or facilitatory mutant subunits of the NMDAR and VGCC channels. Understanding the molecular mechanisms of extinction will be important both for advancing the fundamental understanding of learning and memory as well as for providing novel approaches to treating human disorders of fear dysregulation. Furthermore, this project will provide opportunity to significantly develop Dr. Ressler's expertise and technical skills in behavioral neuroscience, including design, training, and testing of rodents, viral vector techniques, and analysis of gene expression using gene array techniques. Emory University and the Center for Behavioral Neuroscience provide an excellent environment for career development and training in the field of behavioral neuroscience.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01MH069884-02
Application #
6829153
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Desmond, Nancy L
Project Start
2003-12-01
Project End
2007-11-30
Budget Start
2004-12-01
Budget End
2005-11-30
Support Year
2
Fiscal Year
2005
Total Cost
$173,556
Indirect Cost
Name
Emory University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
McCullough, K M; Morrison, F G; Ressler, K J (2016) Bridging the Gap: Towards a cell-type specific understanding of neural circuits underlying fear behaviors. Neurobiol Learn Mem 135:27-39
Keifer Jr, O P; Hurt, R C; Gutman, D A et al. (2015) Voxel-based morphometry predicts shifts in dendritic spine density and morphology with auditory fear conditioning. Nat Commun 6:7582
Gutman, David A; Magnuson, Matthew; Majeed, Waqas et al. (2013) Mapping of the mouse olfactory system with manganese-enhanced magnetic resonance imaging and diffusion tensor imaging. Brain Struct Funct 218:527-37
Mahan, Amy L; Mou, Liping; Shah, Nirali et al. (2012) Epigenetic modulation of Homer1a transcription regulation in amygdala and hippocampus with pavlovian fear conditioning. J Neurosci 32:4651-9
Maguschak, Kimberly A; Ressler, Kerry J (2012) A role for WNT/?-catenin signaling in the neural mechanisms of behavior. J Neuroimmune Pharmacol 7:763-73
Andero, R; Ressler, K J (2012) Fear extinction and BDNF: translating animal models of PTSD to the clinic. Genes Brain Behav 11:503-12
Andero, Raul; Heldt, Scott A; Ye, Keqiang et al. (2011) Effect of 7,8-dihydroxyflavone, a small-molecule TrkB agonist, on emotional learning. Am J Psychiatry 168:163-72
Tang, Yi-lang; Khoury, Lamya; Bradley, Bekh et al. (2011) Substance use disorders assessed using the Kreek-McHugh-Schluger-Kellogg (KMSK) scale in an urban low-income and predominantly African American sample of primary care patients. Am J Addict 20:292-9
Tang, Yi-lang; Li, Wenbiao; Mercer, Kristina et al. (2010) Genotype-controlled analysis of serum dopamine ?-hydroxylase activity in civilian post-traumatic stress disorder. Prog Neuropsychopharmacol Biol Psychiatry 34:1396-401
Ressler, Kerry J; Bradley, Bekh; Mercer, Kristina B et al. (2010) Polymorphisms in CRHR1 and the serotonin transporter loci: gene x gene x environment interactions on depressive symptoms. Am J Med Genet B Neuropsychiatr Genet 153B:812-24

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