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

神经科学家面临着一项艰巨的任务，即描述大脑中许多单个神经元的协调活动，并解释细胞的放电模式如何创造行为。在人类大脑的巨大规模上实现这一目标是BRAIN计划的最终目标。 为了实现这个复杂的目标，首先需要建立适当的实验和分析技术，以及更好地理解简单系统中的基本电路原理。 目前的项目通过开发一种新的实验室模式生物来扩大获得洞察力的机会。 候选物种是鱼Danionella acericida。 这个物种非常小（成年时约1厘米体长），光学透明，这两个特征使该物种非常适合分子和光学技术，用于记录和操纵大量神经元，并使研究人员能够使用最强大的实验方法来研究成年脊椎动物中的每个神经元如何有助于复杂的行为。 该项目将建立这种潜在的革命性模式物种，并通过绘制成年Danionella中气味介导的社会警报行为的神经回路来证明原理。 这项工作的社会效益包括对复杂行为机制的前所未有的洞察，其中一些行为会影响人类神经系统疾病。 此外，从分子生物学到社会行为的多层次分析的整合，使该项目成为一个特别强大的神经科学教学工具的基础，将通过现有的本科和高中研究项目实施，包括对少数群体学生的推广。该项目利用Danionella与斑马鱼Danio rerio的密切系统发育相似性，将现有的实验工具应用于新的动物模型。第一个目标是建立育种，转基因和基因编辑技术，使这些鱼在实验室中繁殖，引入荧光报告基因和光遗传学致动器，并有针对性地操纵特定的内源基因。第二个目的是应用多光子和光片成像成年Danionella，并评估结果对基准建立在幼斑马鱼。第三个目标是开发信息素介导的社会报警行为的测定方法，并记录信息素诱发的大脑中每个神经元的活动。这些实验共同展示了这种新模式物种的实验能力，并创造了研究界采用它所必需的工具。这些见解将通过支持科学家交流的现有和新的网站等途径传播。

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.