Development of Anxiety Models in Drosophila

描述（由申请人提供）：焦虑症是美国最常见的精神疾病。目前，人们认为许多这些疾病是由环境因素引发的，但对这些疾病的易感性是由遗传因素强烈控制的。识别人类新型焦虑易感基因的能力受到限制，部分原因是缺乏焦虑的内在表型，以及构成焦虑症的一系列疾病的复杂性。由于焦虑和恐惧代表了古老的和进化上保守的情绪状态，动物模型在解剖焦虑的潜在神经生物学和识别候选基因方面应该是非常有价值的。简单的动物模型将允许识别“核心”焦虑反应，这些反应已经通过进化扩大和繁殖。核心焦虑反应也将阐明焦虑障碍的可能的内表型。提出的实验将确定新的行为反应对焦虑性刺激在果蝇黑腹。实验将动物置于先天厌恶刺激和条件厌恶刺激下，研究动物在三种行为测量中的反应。果蝇是一个非常强大的遗传模型系统，用于解剖类焦虑反应的行为和神经遗传基础。最终，在这个简单而灵活的遗传模型系统中获得的关于这些反应的知识将允许发展新的和更详细的假设，关于不同形式的焦虑是如何进化的，哪些基因控制反应的大小，可能的内表型，以及人类病理性焦虑状态的潜在功能和原因。

DESCRIPTION (provided by applicant): Anxiety Disorders are the most common mental illness in the US. Currently it is believed that many of these disorders are be triggered by environmental factors, but a predisposition to the disorder is strongly controlled by genetics factors. The ability to identify novel anxiety susceptibility genes in humans has been limited in part by the absence of endophenotypes for anxiety, and by the complexity of the constellation of diseases that comprise anxiety disorders. Since anxiety and fear represent ancient and evolutionarily conserved emotional states, animal models should be extremely valuable in dissecting the underlying neurobiology of anxiety and for identifying candidate genes. Simple animal models will allow for the identification of "core" anxiety responses that have since expanded and multiplied through evolution. A core anxiety response would also illuminate possible endophenotypes for anxiety disorders. The proposed experiments will identify novel behavioral responses to anxiogenic stimuli in Drosophila melanogaster. In these experiments the animals will be subjected to innately and conditionally aversive stimuli, and their responses in three behavioral measures will be determined. Drosophila is an extremely powerful genetic model system for the dissection of the behavioral and neurogenetic underpinnings of anxiety-like responses. Ultimately, the knowledge gained on these responses in this simple and agile genetic model system will permit the development of new and more detailed hypothesis on how different forms of anxiety may have evolved, which genes control the magnitude of responses, possible endophenotypes, and the potential functions and causes of pathological anxiety states in humans. PUBLIC HEALTH RELEVANCE: The proposed project investigates how anxiety-producing stimuli lead to changes in the behavior of Drosophila melanogaster in a novel open field arena. The studies will produce a foundation for further dissecting the genetic and neural basis of anxiety in both invertebrates and vertebrates.