Mechanisms that drive the variation of aversive behavior

驱动厌恶行为变化的机制

基本信息

批准号：
10461812
负责人：
Su Guo
金额：
$ 43.02万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-16 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10461812
关键词：
Address Anatomy Animal Model Animals Anti-Anxiety Agents Anxiety Behavior Behavior Disorders Behavioral Biological Models Brain Budgets Calcium Candidate Disease Gene Choice Behavior Collaborations Complex Computational Science Computer Analysis Data Analyses Diagnosis Disease Dissection Exhibits Fishes Foundations Fright Gene Expression Profiling Genes Genetic Genotype Goals Harvest Heritability Human Image Individual Lighting Link Linkage Disequilibrium Mammals Maps Microscope Molecular Molecular Genetics Mus Normal Range Optics Outcome Pathway Analysis Pharmaceutical Preparations Phenotype Population Population Genetics Property Public Health Quantitative Trait Loci Rattus Recombinant Inbred Strain Regulation Research Research Personnel Resolution Resources Rest Rodent Stimulus System Time Use Effectiveness Validation Variant Work Zebrafish behavioral study candidate validation cell type computational pipelines cost cost effective cost effectiveness driving force experience experimental study genome wide association study genomic locus image processing in vivo calcium imaging information processing insight neural network novel strategies optogenetics preference relating to nervous system tool trait visual motor

项目摘要

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.

项目概要如何规范行为是一个尚未解决的根本问题。它还需要适合分子遗传和系统水平的模型系统。该项目的长期目标是阐明厌恶的分子和细胞基础。行为，由不想要、“不喜欢”或恐惧推动的行为。了解厌恶行为的程度。在基本分子、细胞、系统和群体水平上进行监管应提供基本见解有助于我们理解大脑功能，因此具有重要意义。斑马鱼幼虫提供了一个显着的脊椎动物系统，可以理解来自例如，从分子到系统，它们表现出光/暗偏好行为，即感知到黑暗。厌恶的明/暗偏好作为一种选择行为在整个动物界都被观察到。然而，在哺乳动物中，光/暗偏好被认为是一种类似焦虑的特征，其机制尚不清楚。有趣的是，用同样的方法治疗斑马鱼幼虫。抗焦虑药物也能显着缓解他们对黑暗的厌恶。我们已经证明了斑马鱼幼虫的黑暗厌恶行为的遗传变异。应用中，我们建议利用斑马鱼幼虫的独特优势来实现高通量我们将与群体遗传学专家合作进行表型/基因分型和全脑钙成像。和计算科学来了解这种行为变化的分子和细胞基础。该提案的中心目标是：1）在分子遗传水平上确定这一现象的驱动力 2) 揭示这种行为变化背后的细胞和网络层面的机制。成功完成这些目标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，光谱的极端通常被归类为疾病状态。拟议的工作收获了独特的成果。易驯化脊椎动物模型生物中行为变异的资源，并有望发现新的和这些发现应该对行为调节具有潜在的进化保守性见解。对人类研究从正常范围到疾病状态的行为变化的影响。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。