Diversity Supplement Extension

项目摘要 如何规范行为是一个根本性的未解决的问题。处理这个问题需要易于处理的 行为读数它还需要模型系统，是服从分子遗传和系统水平 解剖这个项目的长期目标是阐明厌恶的分子和细胞基础 行为，一种由不想要，“不喜欢”或恐惧推动的行为。了解厌恶行为是如何 在基本的分子、细胞、系统和群体水平上进行调节，将提供基本的见解 我们对大脑功能的理解，因此具有很高的意义。 斑马鱼幼鱼提供了一个突出的脊椎动物系统，使人们能够理解行为， 分子到系统。例如，它们表现出亮/暗偏好行为， 令人厌恶光/暗偏好作为一种选择行为在整个动物王国都可以观察到。底层 然而，机制还不清楚。在哺乳动物中，光/暗偏好被认为是一种类似焦虑的特征。 并用于评估药物的抗焦虑特性。有趣的是，用同样的方法处理幼斑马鱼， 抗焦虑药物也能显著缓解他们对黑暗的厌恶。 我们已经证明了斑马鱼幼鱼的黑暗厌恶行为的遗传变异。在这 应用，我们建议利用斑马鱼幼体的独特优势，以实现高通量 表型分型/基因分型和全脑钙成像。我们将与群体遗传学专家合作 和计算科学来理解这种行为变异的分子和细胞基础。的 该建议的中心目标是：1）在分子遗传水平上确定这一点的驱动力 行为变异2)揭示这种行为变化背后的细胞和网络级机制。 这些目标的成功实现将把基因与大脑和行为联系起来。 影响和结果：在整个人群中观察到复杂的行为， 通常被归类为疾病状态的极端情况。拟议的工作收获了独特的 资源的行为变异在一个听话的脊椎动物模式生物，并有望发现新的， 对行为调节的潜在进化保守见解。这些发现应该是积极的 对人类行为变异研究的影响，从正常范围到疾病状态。 这项工作也为其他研究人员利用斑马鱼绘制自然存在的地图奠定了基础 数量性状

PROJECT SUMMARY How behavior is regulated is a fundamental unsolved problem. Approaching this problem requires tractable behavioral readouts. It also requires model systems that are amenable to molecular genetic and systems level dissection. The long-term goal of this project is to elucidate the molecular and cellular basis of aversive behavior, an action that is propelled by un-wanting, “dislike”, or fear. Understanding how aversive behavior is regulated at the basic molecular, cellular, systems, and population levels shall provide fundamental insights into our understanding of brain function, and are therefore of high significance. Larval zebrafish provide a salient vertebrate system that enables the understanding of behavior from molecules to systems. For example, they exhibit a light/dark preference behavior, with dark being perceived aversive. Light/dark preference as a choice behavior is observed across the animal kingdom. The underlying mechanisms are however not understood. In mammals, light/dark preference is considered an anxiety-like trait and used to assess the anxiolytic properties of drugs. Intriguingly, treatment of larval zebrafish with the same anti-anxiety medications also significantly relieves their dark aversion. We have demonstrated heritable variation of the dark aversion behavior in larval zebrafish. In this application, we propose to exploit the unique strengths of larval zebrafish for high throughput phenotyping/genotyping and brain-wide calcium imaging. We will team up with experts in population genetics and computational science to understand the molecular and cellular basis of this behavioral variation. The central objectives of this proposal are: 1) Determine, at the molecular genetic level, the driving forces for this behavioral variation. 2) Uncover cellular and network level mechanisms that underlie this behavioral variation. Successful completion of these aims will link genes to brain and to behavior. Impact and Outcomes: Complex behaviors are observed in a spectrum across the population, with the extreme ends of the spectrum often classified as disease states. The proposed work harvests a unique resource of behavioral variation in a tractable vertebrate model organism, and is expected to uncover new and potentially evolutionarily conserved insights into behavioral regulation. These findings should have a positive impact on informing human studies of behavioral variation ranging from normal spectrum to disease states. The proposed work also lay foundation for other researchers to use zebrafish for mapping naturally existing quantitative traits.