Identification of the neural circuitry underlying motion vision in Drosophila

描述（由申请人提供）：神经科学的一个主要目标是理解将感官信息与生物体行为联系起来的神经过程。果蝇（Drosophila melanogaster）处理视觉运动的通路为剖析此类计算背后的神经回路提供了一个出色的模型系统。尽管付出了巨大的努力并且运动视觉的计算模型取得了成功，但运动检测的神经学基础尚未阐明。理解神经回路功能的核心挑战是识别参与每次计算的神经元，确定它们如何相互连接，并评估它们的功能特性。该提案开发了一种基于新转基因技术的新型正向遗传方法，将实现这些目标。由于正向遗传筛选允许以相对公正的方式识别遗传系统的组成部分，因此它们已被证明是理解许多不同生物过程（包括发育和疾病机制）的极其强大的工具，但尚未广泛应用于行为。使用灵敏的定量行为分析，将进行基因筛选，以识别神经元，这些神经元在受到破坏时会导致运动视觉缺陷。为了识别构成运动视觉电路的神经元，有必要对小的、明确定义的神经元组进行基因操作，这是使用当前技术不可能实现的。正因为如此，新的遗传工具已经被开发出来，可以对行为屏幕中识别的神经元群进行系统的解剖。最终，研究这些神经元如何连接以及它们的功能特性应该有助于深入了解处理视觉信息和介导视觉行为的神经回路的结构。 这些研究将在斯坦福大学神经生物学系进行。申请人将得到两名在昆虫和灵长类动物的遗传学、发育生物学、视觉行为心理物理学分析以及电生理学领域拥有专业知识的教员的指导。申请人将通过旁听课程、参加研讨会、在部门座谈会上展示自己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来接受进一步的培训。 公共健康相关性：对苍蝇和脊椎动物的研究表明，运动视觉代表了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，了解果蝇的运动视觉将广泛用于理解正常和患病状态下视觉和神经计算的基本神经机制。

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.