Dissecting the functional anatomy of the visual system: a new way forward

剖析视觉系统的功能解剖：前进的新方法

• 批准号: 7917514
• 负责人: Thomas Robert Clandinin
• 金额: $ 79万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7917514
• 关键词: Anatomy; Animals; Behavior; Behavioral; Behavioral Paradigm; Biophysics; Brain; Cells; Color Perception; Complex; Coupled; Detection; Drosophila genus; Genetic Models; Genetic Screening; Goals; Human; Invertebrates; Ion Channel; Lead; Link; Mental disorders; Molecular; Motion; Nervous system structure; Neurologic; Neurons; Neurosciences; Output; Process; Sensory; System; Techniques; Vertebrates; Visual system structure; Work; fly; genetic analysis; interest; neural circuit; novel strategies; positional cloning; relating to nervous system; repaired; visual information

How do neural circuits guide our behavior? The answers promise to revolutionize our understanding of what it means to be human and how to repair the damaged neural circuits that underlie human neurological and psychiatric disorders. The incredible complexity of the mammalian brain, however, coupled with limited ability to genetically manipulate specific neural circuits in vertebrates, has made our progress difficult. My lab is developing new approaches that will rejuvenate this effort. We take advantage of the fact that many basic neural computations are evolutionarily ancient: invertebrates are capable of some of the same computations that humans are. This enables us to study processes familiar to vertebrate physiologists using the fruit fly, an animal with a relatively simple, genetically hard-wired nervous system. As a model genetic system, Drosophila offers a complex, interesting behavioral repertoire combined with an extensive toolkit for both forward and reverse genetic analysis. Our goal is to provide a complete mechanistic understanding of how visual information is processed at the level of identified cells and circuits. In preliminary work, we have developed new behavioral paradigms that allow high-throughput, automated forward genetic screens to identify neurons specifically involved in such processes as motion detection and color perception. To define the behavioral contributions of these functionally important neurons, we are adapting analytical techniques from ion channel biophysics and systems neuroscience to the analysis of fly behavior. Using new molecular and electrophysiological techniques that we will develop, we propose to link circuit anatomy to circuit function, and to define how changes in the activities of functionally important neurons lead to behavioral decisions. These studies will provide the first synthesis linking a sensory input to a behavioral output, through the functions of specific molecules, neurons and circuits.

神经回路如何指导我们的行为？答案承诺 彻底改变我们对人类意义的理解，以及如何修复 导致人类神经和精神疾病的受损神经回路。 然而，哺乳动物大脑的难以置信的复杂性，加上有限的能力 基因操控脊椎动物的特定神经回路， 难我的实验室正在开发新的方法，将振兴这一努力。我们采取 许多基本的神经计算在进化上是古老的： 无脊椎动物也能进行一些和人类一样的计算。这 使我们能够利用果蝇研究脊椎动物生理学家熟悉的过程， 具有相对简单的、遗传上固定的神经系统的动物为模特 果蝇提供了一个复杂的，有趣的行为库， 具有用于正向和反向遗传分析的广泛工具包。我们的目标是 提供了一个完整的机械理解视觉信息是如何处理的， 被识别的细胞和回路的水平。在初步工作中，我们开发了新的 行为模式，允许高通量，自动化的遗传筛选， 识别与运动检测和颜色等过程有关的神经元 perception.为了定义这些功能重要的行为贡献， 神经元，我们正在采用离子通道生物物理学的分析技术， 系统神经科学来分析苍蝇的行为。使用新的分子和 电生理技术，我们将开发，我们建议链接电路解剖 电路功能，并定义如何在功能上重要的活动的变化， 神经元导致行为决定。这些研究将提供第一个合成 将感官输入与行为输出联系起来，通过特定的 分子、神经元和电路。