Diversity Supplement Extension

项目总结 如何监管行为是一个根本的悬而未决的问题。解决这个问题需要有条理的态度 行为读数。它还需要符合分子遗传和系统水平的模型系统 解剖。这个项目的长期目标是阐明Aversive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。了解厌恶行为有多严重 在基本的分子、细胞、系统和种群水平上的监管应提供基本的见解 对于我们了解大脑的功能，因此具有很高的意义。 斑马鱼幼体提供了一个显著的脊椎动物系统，使人们能够从 分子与系统的关系。例如，他们表现出明/暗的偏好行为，黑暗被感知 令人厌恶。明/暗偏好作为一种选择行为，在整个动物界都被观察到。潜在的 然而，机制尚不清楚。在哺乳动物中，明/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性能。有趣的是，用同样的方法处理斑马鱼幼体 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体的黑暗厌恶行为可遗传变异。在这 应用，我们建议开发斑马鱼幼体的独特优势，以实现高吞吐量 表型/基因分型和全脑钙成像。我们将与种群遗传学专家合作 以及计算机科学来理解这种行为变异的分子和细胞基础。这个 这项提议的中心目标是：1)在分子遗传水平上确定这一现象的驱动力 行为变异。2)揭示这种行为差异背后的蜂窝和网络层面的机制。 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， 谱系的两端通常被归类为疾病状态。这项拟议的工作收获了一种独特的 在易驯服的脊椎动物模式生物中行为变异的来源，并有望发现新的和 潜在地从进化上保守了对行为调控的见解。这些发现应该会有积极的 对告知人类研究从正常谱系到疾病状态的行为变异的影响。 这项工作还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.