Anxiety disorders are among the leading causes of illness in the U.S., yet their origins and the way in which an individual's genotype interacts with the environment to influence disease remain poorly understood. The long-term goal of these studies is to better understand the genetic and neurobiological underpinnings of variation in anxiety and stress-responsiveness. This work will employ the zebrafish model, but with an innovative focus on fish recently derived from wild stocks. The value of these wild-derived individuals is in the heightened levels and greater variation in anxiety-related behaviors they display relative to an established laboratory stocks. The specific goals of this exploratory project are first to compare gene expression profiles in the brains of two wild-derived zebrafish lines divergent in the display of anxiety-related behavior (high and low respectively) to two established laboratory lines that also show behavioral variation. The wild-derived zebrafish lines exhibit what have been termed 'proactive'and 'reactive'coping styles in other model systems and also pronounced sex differences with females exhibiting higher levels of anxiety-related behavior. The second goal of these studies is to compare gene expression profiles in the brain between the two divergent wild-derived lines at time points ranging from early development until after maturation when sex differences in anxiety-related behaviors have emerged. The goal of this second aim is to begin exploring the developmental origins of coping style differences in adulthood. The benefits of this project should include behavioral and neurogenomic characterization of a zebrafish model system that will lead to mechanistic studies in zebrafish and potentially studies of identified candidate genes in human association studies. The zebrafish model system is also particularly well suited to studying the genomic and developmental underpinnings of anxiety-related behaviors and the ways in which these mechanisms are influenced by an organism's environment.

Public Health Relevance

This project addresses the genetic and developmental origins of anxiety-related behaviors using the zebrafish as a model system. Anxiety disorders are prevalent and therefore represent a significant public health issue imposing significant illness and economic burdens on the U.S. population.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21MH080500-02
Application #
8264749
Study Section
Neuroendocrinology, Neuroimmunology, and Behavior Study Section (NNB)
Program Officer
Beckel-Mitchener, Andrea C
Project Start
2011-05-20
Project End
2014-04-30
Budget Start
2012-05-01
Budget End
2014-04-30
Support Year
2
Fiscal Year
2012
Total Cost
$182,965
Indirect Cost
$57,965
Name
North Carolina State University Raleigh
Department
Biology
Type
Schools of Earth Sciences/Natur
DUNS #
042092122
City
Raleigh
State
NC
Country
United States
Zip Code
27695
Wong, Ryan Y; McLeod, Melissa M; Godwin, John (2014) Limited sex-biased neural gene expression patterns across strains in Zebrafish (Danio rerio). BMC Genomics 15:905
Wong, Ryan Y; Oxendine, Sarah E; Godwin, John (2013) Behavioral and neurogenomic transcriptome changes in wild-derived zebrafish with fluoxetine treatment. BMC Genomics 14:348