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

神经回路如何指导我们的行为？答案承诺 彻底改变我们对做人意味着什么以及如何修复 神经回路受损，是人类神经和精神疾病的基础。 然而，哺乳动物大脑令人难以置信的复杂性，加上有限的能力 对脊椎动物的特定神经回路进行基因操作，已经取得了进展 很难。我的实验室正在开发新的方法，使这一努力重新焕发活力。我们拿着 许多基本的神经计算在进化上都是古老的，这一事实的优势是： 无脊椎动物能够进行一些与人类相同的计算。这 使我们能够研究脊椎动物生理学家所熟悉的使用果蝇的过程 具有相对简单的、基因上固定的神经系统的动物。作为一名模特 遗传系统，果蝇提供了一个复杂而有趣的行为组合 拥有用于正向和反向遗传分析的广泛工具包。我们的目标是 提供对视觉信息如何处理的完整机械理解 已识别的单元和电路的水平。在前期工作中，我们开发了新的 行为范例，允许高通量、自动化的前向基因筛查 识别特定参与运动检测和颜色等过程的神经元 感知力。为了定义这些在功能上很重要的行为贡献 神经元，我们正在采用离子通道生物物理学和 系统神经科学来分析苍蝇的行为。使用新的分子和 我们将开发的电生理技术，我们建议将电路解剖学 以电路的功能，并定义如何改变活动的重要功能 神经元会导致行为决策。这些研究将提供第一个合成 通过特定的功能将感觉输入与行为输出联系起来 分子、神经元和电路。

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.