BRAIN EAGER: Danionella translucida: A New Fish Model for Systems Neuroscience

BRAIN EAGER：透明丹尼氏菌：系统神经科学的新鱼类模型

• 批准号: 1545885
• 负责人: Adam Douglass
• 金额: $ 30万
• 依托单位: University of Utah
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-15 至 2018-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1545885&HistoricalAwards=false
• 关键词: BRAIN; EAGER; Danionella; translucida; New

Neuroscientists face the difficult task of describing the coordinated activities of many single neurons across the brain, and explaining how the cells' firing patterns create behavior. Achieving this goal at the immense scale of the human brain is the ultimate goal of the BRAIN Initiative. To accomplish this complex goal, it first is necessary to establish appropriate experimental and analytical techniques, as well as a better understanding of basic circuit principles, in simpler systems. The current project expands the opportunities for gaining insight by developing a new laboratory model organism. The candidate species is the fish Danionella translucida. This species is very small (~1 cm body length as an adult) and optically transparent, two characteristics that make the species exquisitely well-suited to molecular and optical techniques for recording from and manipulating large sets of neurons, and enabling researchers to use the most powerful experimental methods to study how each neuron in an adult vertebrate contributes to complex behaviors. The project will establish this potentially revolutionary model species and demonstrate proof-of-principle by mapping the neural circuits that underlie odor-mediated social alarm behavior in adult Danionella. The societal benefits of this work include unprecedented insight into the mechanisms of complex behaviors, some of which are affected in human neurological diseases. Additionally, the integration of multiple levels of analysis, from molecular biology to social behavior, render this project the basis of a particularly powerful neuroscience teaching tool, to be implemented through existing undergraduate and high school research programs that include outreach to students from minority groups. This project draws on Danionella's close phylogenetic similarity to the zebrafish, Danio rerio, to apply existing experimental tools to a new animal model. The first aim is to establish breeding, transgenesis, and gene editing techniques that will allow propagation of these fish in the lab, introduction of fluorescent reporters and optogenetic actuators, and targeted manipulation of specific, endogenous genes. The second aim is to apply multiphoton and light-sheet imaging to adult Danionella, and evaluate the results against benchmarks established in larval zebrafish. The third aim is to develop assays for a pheromone-mediated social alarm behavior, and record pheromone-evoked activity from every neuron in the brain. These experiments collectively demonstrate the experimental power of this new model species and create tools that are essential for its adoption by the research community. The insights will be disseminated through, among others, existing and new websites supporting exchange among scientists.

神经科学家面临着描述大脑中许多单个神经元的协调活动的艰巨任务，并解释了细胞的发射模式如何创造行为。在人脑的巨大规模上实现这一目标是大脑计划的最终目标。 为了实现这一复杂的目标，首先必须在更简单的系统中建立适当的实验和分析技术，并更好地了解基本电路原理。 当前的项目通过开发新的实验室模型生物体扩大了获得洞察力的机会。 候选物种是鱼类丹妮娜半透明。 This species is very small (~1 cm body length as an adult) and optically transparent, two characteristics that make the species exquisitely well-suited to molecular and optical techniques for recording from and manipulating large sets of neurons, and enabling researchers to use the most powerful experimental methods to study how each neuron in an adult vertebrate contributes to complex behaviors. 该项目将建立这种潜在的革命性模型物种，并通过绘制源自气味介导的成人Danionella的社会警报行为的神经回路来证明原理证明。 这项工作的社会益处包括对复杂行为机制的前所未有的见解，其中一些在人类神经疾病中受到影响。 此外，从分子生物学到社会行为的多个分析的整合，使该项目成为一个特别强大的神经科学教学工具的基础，该项目将通过现有的本科和高中研究计划来实施，其中包括向少数群体的学生推广。该项目借鉴了Danionella与斑马鱼Danio Rerio的紧密系统发育相似性，以将现有的实验工具应用于新的动物模型。第一个目的是建立繁殖，转基因和基因编辑技术，这些技术将允许在实验室中传播这些鱼类，引入荧光记者和光学遗传执行器，并针对特定的内源基因的有针对性操纵。第二个目的是将多光子和灯页成像应用于成年Danionella，并根据幼虫斑马鱼中建立的基准评估结果。第三个目的是开发信息素介导的社会警报行为的测定，并记录大脑中每个神经元的信息素诱发的活动。这些实验共同证明了这种新模型物种的实验能力，并创建了研究社区采用至关重要的工具。这些见解将通过支持科学家之间的交流的现有和新网站来传播。