A new paradigm for quantifying animal behavior in a model genetic system

描述（由申请人提供）：由于缺乏对基因和行为之间的联系进行客观和定量评估的方法，阻碍了理解和治疗许多人类神经系统疾病的进展。传统的动物行为研究仅在低维数据中探测用户定义的行为的一小部分，并且不适合发现基因和行为之间的微妙表型或复杂关系。为了超越这些简单的动物行为表现，我们建议建立一个高分辨率的三维成像系统，可以跟踪单一行为的动物。该系统将使用数据驱动的方法定量地将行为与遗传学联系起来，以发现定型运动。我们的具体目标是：1）开发一种新的行为观察和自动表型分析标准，以量化自由移动的果蝇的行为，2）通过研究果蝇神经退行性疾病模型和果蝇近缘种的行为，证明我们新技术的灵敏度和准确性; 3）扩展我们的系统，使两个独立的苍蝇在一个单一的竞技场的同时跟踪和分析，并测试该系统与雄性和雌性苍蝇之间的求偶行为的测定。在模型遗传生物中测量行为的细微变化的能力将使我们比以往任何时候都更接近于在遗传和分子水平上理解神经疾病和行为障碍。

DESCRIPTION (provided by applicant): Progress toward understanding and curing many human neurological diseases is hindered by a lack of methods for objective and quantitative assessment of the connections between genes and behavior. Traditional studies of animal behavior probe only a small subset of user-defined behaviors in low- dimensional data and are inappropriate for the discovery of subtle phenotypes or complex relationships between genes and behavior. To move beyond these simple representations of animal behavior, we propose to build a high-resolution, three-dimensional imaging system that can track single behaving animals. This system will quantitatively connect behavior to genetics using a data-driven method for the discovery of stereotyped motions. Our specific aims are to 1) develop a new standard for behavioral observation and automatic phenotyping to quantify the behavior of freely moving fruit flies, 2) demonstrate the sensitivity and accuracy of our new technology by studying Drosophila models of neurodegenerative diseases and the behavior of closely-related species of Drosophila fruit flies and 3) expand our system to enable simultaneous tracking and analysis of two independent flies in a single arena and test this system with assays of courtship behavior between male and female flies. The ability to measure subtle changes in behavior in a model genetic organism will bring us closer than we have ever been to understanding neurological diseases and behavioral disorders at the genetic and molecular level.