Identification of the neural circuitry underlying motion vision in Drosophila

描述(申请人提供)：神经科学的一个主要目标是了解将感觉信息与有机体行为联系起来的神经过程。果蝇中处理视觉运动的通路为解剖构成这种计算的神经回路提供了一个极好的模型系统。尽管对运动视觉进行了大量的研究和成功的计算建模，但运动检测的神经学基础仍有待阐明。理解神经回路功能的中心挑战是识别参与每一次计算的神经元，确定它们如何相互连接，并评估它们的功能特性。这项提议开发了一种基于新的转基因技术的新的正向遗传方法，将实现这些目标。由于正向基因筛查允许以相对公正的方式识别遗传系统的组成部分，它们已被证明是理解许多不同生物过程的极其强大的工具，包括发育和疾病的机制，但尚未被广泛应用于行为。使用一种灵敏的、定量的行为分析，将进行基因筛查，以识别当受到干扰时会导致运动视觉缺陷的神经元。为了识别组成运动视觉电路的神经元，有必要对定义良好的小神经元群体进行基因操作，这是目前的技术所不可能做到的。正因为如此，新的遗传工具已经开发出来，可以系统地解剖行为屏幕上识别的神经元集合。最终，研究这些神经元是如何连接的，它们的功能特性是什么，应该会导致对处理视觉信息和调节视觉行为的神经电路结构的深入了解。这些研究将在斯坦福大学神经生物学系进行。申请者将由两名专业人员指导，他们的专业领域包括遗传学、发育生物学、视觉行为的心理物理分析以及昆虫和灵长类动物的电生理学。申请者将接受进一步的培训，包括旁听课程、参加研讨会、在部门座谈会上介绍他的工作，以及参加伍兹霍尔海洋生物实验室的神经科学定量方法课程。 与公共健康相关：对苍蝇和脊椎动物的研究表明，运动视觉代表着一种进化上古老的计算，其基本算法在所有动物中都是保守的。因此，了解苍蝇的运动视觉对于理解正常和疾病状态下视觉和神经计算的基本神经机制将具有广泛的用途。

DESCRIPTION (provided by applicant): A major goal of neuroscience is to understand the neural processes that link sensory information to the behavior of an organism. The pathways that process visual motion in the fruit fly, Drosophila melanogaster, provide an excellent model system for dissecting the neural circuits that underlie such computations. Despite significant effort and the successful computational modeling of motion vision, the neurological basis for motion detection has yet to be elucidated. The central challenges to understanding neural circuit function are to identify the neurons that participate in each computation, to determine how they are connected to one another, and to assess their functional properties. This proposal develops a novel forward genetic approach based on new transgenic technologies that will achieve these goals. Because forward genetic screens allow the identification of the components of a genetic system in a relatively unbiased manner, they have proven to be extremely powerful tools for understanding many different biological processes, including the mechanisms of development and disease, but have not yet been extensively applied to behavior. Using a sensitive, quantitative behavioral assay, a genetic screen will be carried out to identify neurons that, when disrupted, lead to defects in motion vision. In order to identify the neurons that comprise the motion vision circuitry, it will be necessary to genetically manipulate small, well defined groups of neurons, something that is not possible using current technologies. Because of this, new genetic tools have been developed that allow for systematic dissection of the ensembles of neurons identified in the behavioral screen. Ultimately, studying how these neurons are connected and what their functional properties are should lead to insights into the structure of the neural circuits that process visual information and mediate visual behaviors. These studies will be carried out in the Department of Neurobiology at Stanford University. The applicant will be mentored by two faculty members with expertise spanning the fields of genetics, developmental biology, psychophysical analysis of visual behaviors, and electrophysiology, in insects and primates. The applicant will receive further training by auditing classes, attending seminars, presenting his work in departmental colloquia, and attending a course on quantitative methods in neuroscience at the Woods Hole Marine Biological Lab. PUBLIC HEALTH RELEVANCE: Studies of flies and vertebrates suggest that motion vision represents an evolutionarily ancient computation whose underlying algorithm is conserved across all animals. Therefore, understanding motion vision in flies will be of broad use in understanding the basic neuronal mechanisms of vision and neural computation in both the normal and diseased state.