Wild-derived zebrafish as models for anxiety and stress responsiveness

描述（由申请人提供）：焦虑症是美国疾病的主要原因之一，然而，它们的起源以及个体基因型与环境相互作用影响疾病的方式仍然知之甚少。这些研究的长期目标是更好地了解焦虑和压力反应变化的遗传和神经生物学基础。这项工作将采用斑马鱼模型，但创新的重点是鱼类最近从野生种群。这些野生来源的个体的价值在于，相对于已建立的实验室储备，它们所表现出的焦虑相关行为的水平更高，变化更大。这个探索性项目的具体目标是首先比较两个野生来源的斑马鱼品系大脑中的基因表达谱，这两个品系在显示焦虑相关行为（分别为高和低）方面与两个建立的实验室品系不同，这两个品系也显示出行为变异。野生来源的斑马鱼系表现出在其他模型系统中被称为“主动”和“反应”的应对方式，并且表现出更高水平的焦虑相关行为的女性也存在明显的性别差异。这些研究的第二个目标是比较两个不同的野生衍生系在从早期发育到成熟后焦虑相关行为的性别差异出现的时间点之间大脑中的基因表达谱。第二个目标是开始探索成年期应对方式差异的发展起源。这个项目的好处应该包括行为和神经基因组特征的斑马鱼模型系统，这将导致在斑马鱼的机制研究和潜在的研究，在人类协会研究确定的候选基因。斑马鱼模型系统也特别适合于研究焦虑相关行为的基因组和发育基础，以及这些机制受生物体环境影响的方式。 公共卫生相关性： 该项目以斑马鱼为模型系统，探讨焦虑相关行为的遗传和发育起源。 焦虑症很普遍，因此代表了一个重大的公共卫生问题，给美国人口带来了重大的疾病和经济负担。

DESCRIPTION (provided by applicant): 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.