This proposal seeks support for the continued career development of the Candidate, Larry J. Young, PhD. Dr. Young is an Associate Professor in the Department of Psychiatry and Behavioral Sciences and a faculty member in the Center for Behavioral Neuroscience (CBN) at Emory University. Emory and the CBN provide an ideal environment for the continued development of the Candidate's research program. Dr. Young's work focuses on the molecular, cellular and neurobiological mechanisms underlying complex social behaviors. The long-term goal of the Candidate is to incorporate state-of-the-art technologies to understand the molecular mechanisms underlying individual variation in social behaviors. Using the highly social and monogamous prairie vole as an animal model, the Candidate's research suggests that the vasopressin receptor (V1aR) plays a critical role in modulating affiliative behaviors. Molecular studies suggest that variation in the gene encoding V1aR (avprla) contributes to individual variation in social behavior.
The Aims i n this proposal are designed to test four specific hypotheses.
The first Aim will test the hypothesis that polymorphisms in an avprla microsatellite directly contribute to variation in V1aR distribution in the brain using a knock-in mouse approach.
The second Aim uses a viral vector-based siRNA approach to directly test the hypothesis that variation in avprla expression contributes to variation in social behavior in prairie voles. Studies in the third Aim will test the hypothesis that diversity in avprla expression in the vole is a primary source of heritable variation in social behavior using a selective breeding strategy.
The fourth Aim will directly test the hypothesis that polymorphisms in the human AVPR1A contribute to variation in human social cognition. Each of these Aims involves the implementation of new experimental approaches into the Candidate's research program. The Career Development Plan will entail collaborations with colleagues at Emory and abroad to develop the Candidate's expertise in creating knock-in mice using homologous recombination, modulating gene expression using siRNA technology, genomics and human genetic analyses. The research outlined in this proposal has important implications for understanding the etiology of the social impairments associated with Autism Spectrum Disorders (ASD). Ultimately, these findings may lead to novel therapeutic targets for the treatment of the social impairments which characterize this devastating disorder. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Scientist Development Award - Research (K02)
Project #
2K02MH064692-06
Application #
7319842
Study Section
Neuroendocrinology, Neuroimmunology, and Behavior Study Section (NNB)
Program Officer
Simmons, Janine M
Project Start
2002-08-01
Project End
2012-08-31
Budget Start
2007-09-01
Budget End
2008-08-31
Support Year
6
Fiscal Year
2007
Total Cost
$121,500
Indirect Cost
Name
Emory University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Hopkins, William D; Keebaugh, Alaine C; Reamer, Lisa A et al. (2014) Genetic influences on receptive joint attention in chimpanzees (Pan troglodytes). Sci Rep 4:3774
Anacker, Allison M J; Ahern, Todd H; Hostetler, Caroline M et al. (2014) Drinking alcohol has sex-dependent effects on pair bond formation in prairie voles. Proc Natl Acad Sci U S A 111:6052-7
NESCent Working Group on Integrative Models of Vertebrate Sociality: Evolution, Mechanisms, and Emergent Properties; Hofmann, Hans A; Beery, Annaliese K et al. (2014) An evolutionary framework for studying mechanisms of social behavior. Trends Ecol Evol 29:581-9
Modi, Meera E; Connor-Stroud, Fawn; Landgraf, Rainer et al. (2014) Aerosolized oxytocin increases cerebrospinal fluid oxytocin in rhesus macaques. Psychoneuroendocrinology 45:49-57
Skuse, David H; Lori, Adriana; Cubells, Joseph F et al. (2014) Common polymorphism in the oxytocin receptor gene (OXTR) is associated with human social recognition skills. Proc Natl Acad Sci U S A 111:1987-92
Charles, Rhonda; Sakurai, Takeshi; Takahashi, Nagahide et al. (2014) Introduction of the human AVPR1A gene substantially alters brain receptor expression patterns and enhances aspects of social behavior in transgenic mice. Dis Model Mech 7:1013-22
Donaldson, Zoe R; Young, Larry J (2013) The relative contribution of proximal 5' flanking sequence and microsatellite variation on brain vasopressin 1a receptor (Avpr1a) gene expression and behavior. PLoS Genet 9:e1003729
Tadesse, Tizeta; Cheng, Qi; Xu, Mei et al. (2013) Regulation of ephrin-A expression in compressed retinocollicular maps. Dev Neurobiol 73:274-96
Inoue, K; Burkett, J P; Young, L J (2013) Neuroanatomical distribution of ?-opioid receptor mRNA and binding in monogamous prairie voles (Microtus ochrogaster) and non-monogamous meadow voles (Microtus pennsylvanicus). Neuroscience 244:122-33
Barrett, Catherine E; Keebaugh, Alaine C; Ahern, Todd H et al. (2013) Variation in vasopressin receptor (Avpr1a) expression creates diversity in behaviors related to monogamy in prairie voles. Horm Behav 63:518-26

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