Learning in zebrafish

我提出的研究计划旨在阐明斑马鱼嗅觉学习的能力、发展和结构基础。这些动物的体积小、相对透明和遗传易驯化，使斑马鱼被广泛用于研究脊椎动物发育的模型。这些特性也为神经生物学研究的各个方面提供了优势，但到目前为止，关于斑马鱼学习的描述相当少，因此利用这些动物来研究记忆的大脑机制一直相对有限。我们最近能够在成年斑马鱼身上获得快速而强大的嗅觉学习，使用我们开发的一种行为任务，利用动物辨别气味的能力来训练它们将特定的新气味与食物奖励的可用性联系起来；学习是根据转向频率、游泳轨迹和摄取奖励的潜伏期进行评估的。在这笔赠款的帮助下，我们将扩大这些行为研究，并将它们与药理学、分子生物学和神经化学解剖学工具相结合，以确定当鱼类学会将特定气味与食物奖励联系起来时激活的主要大脑结构和途径。我们还将调查这些结构的发展与这些学习能力之间的可能相关性。这些结果将被用来通知和约束后续的电生理和光学研究，以及学习和记忆的计算模型。总体而言，这项工作应该有助于我们理解记忆是如何发展和发挥作用的，对神经学和计算机科学也有影响。

My proposed research program is aimed at clarifying the capacity, development, and structural underpinnings of olfactory learning in zebrafish. The small size, relative transparency, and genetic tractability of these animals have made zebrafish widely used models for study of vertebrate development. These qualities also offer advantages for various aspects of neurobiological research, but until now there has been rather little description of learning in zebrafish, so use of these animals for study of brain mechanisms of memory has been relatively limited. We have recently been able to obtain rapid and robust olfactory learning in adult zebrafish, using a behavioural task we developed in which the animals' ability to discriminate odors is exploited to train them to associate specific novel odors with availability of food rewards; learning is assessed in terms of frequency of turning, swim trajectory, and latency to ingest the reward. With the aid of this grant, we will extend these behavioural studies, and combine them with tools of pharmacology, molecular biology and neurochemical anatomy, to identify the principal brain structures and pathways activated when fish learn to associate specific odors with food reward. We will also investigate the possible correlation between development of these structures and of these learning capacities. The results will be used to inform and constrain subsequent electrophysiological and optical investigations, as well as computational models of learning and memory. Overall, this work should contribute significantly to our understanding of how memory develops and functions, with implications for neurology and computer science as well.