Associative learning and memory in zebrafish

学习和记忆是复杂的生物过程，其机制仍然知之甚少。2005年，我们提出用一种简单的脊椎动物斑马鱼来研究学习和记忆。我们认为，这种脊椎动物的简单性，以及它代表了一种进化上的古老生物学，将使我们能够发现最基本的，即学习和记忆的核心特征和机制。由于这种物种的简单性，我们还认为，与其他实验室生物相比，斑马鱼的这种发现可能会以更有效的方式进行。我们完成了NSERC的资助，其中我们描述了斑马鱼的特征(例如，它们如何移动，它们对什么刺激做出反应，以及什么激励它们)，这些特征对于运行学习任务和解释这些测试的结果是至关重要的。在NSERC的第二个赠款周期(从2011年开始)，我们为斑马鱼制定了许多学习任务，并证明了尽管斑马鱼物种很简单，但它能够学习复杂的空间任务。这种类型的学习支持人类的情节记忆，这种记忆形式允许我们记住我们是谁，以及我们一生中发生了什么。在当前的应用中，我们现在建议将我们的工作扩展到斑马鱼记忆的表征。我们将使用简单(非空间)、复杂的联想关系(空间)和程序(技能相关)记忆任务来研究短期、中期和长期记忆。我们将开发计算机化的刺激传递和行为反应量化方法，使我们能够在没有人工干预的情况下自动进行记忆测试。我们将使用药物来操纵记忆的阶段和形式。我们还将测试已知基因被打乱的突变斑马鱼，作为未来高通量筛选涉及学习和记忆的新突变(和基因)的概念研究的证明。人们已经为斑马鱼开发了许多复杂的遗传方法，但对其学习和记忆特性知之甚少。因此，对这些复杂过程的机械分析是不可能的。我们建议的目标是填补这一空白，并使行为遗传学桥梁的行为支柱像它的遗传学支柱一样强大。最终，我们对斑马鱼的研究将回答许多关于记忆是如何形成、存储和回忆的问题，这些问题对我们的日常生活至关重要。

Learning and memory are complex biological processes whose mechanisms are still poorly understood. In 2005, we proposed to use a simple vertebrate, the zebrafish, to start studying learning and memory. We argued that the simplicity of this vertebrate, and the fact that it represents an evolutionarily ancient biology, will allow us to discover the most fundamental, that is, core features and mechanisms of learning & memory. Because of the simplicity of this species, we also argued that with the zebrafish such discoveries may be made in a more efficient manner than what would be possible with other laboratory organisms. We completed an NSERC grant in which we characterized features of zebrafish (for example, how they move, what stimuli they respond to and what motivates them) that were crucial for running learning tasks and for interpreting the results of these tests. In the second NSERC grant cycle (starting in 2011) we developed numerous learning tasks for zebrafish, and demonstrated that despite the simplicity of this species, zebrafish are capable of learning complex spatial tasks. This type of learning is what supports episodic memory in humans, a form of memory that allows us to remember who we are and what happened to us throughout our life. In the current application, we now propose to extend our work to the characterization of memory in zebrafish. We will study short-, medium- and long-term memory using simple (non-spatial), complex associative relational (spatial) and procedural (skill-related) memory tasks. We will develop computerized stimulus delivery and behavioural response quantification methods that will allow us to run the memory tests in an automated manner without human interference. We will use drugs to manipulate memory phases and forms. We will also test mutant zebrafish in which known genes are disrupted, as a proof of concept study for future high throughput screening for novel mutations (and genes) involved in learning & memory. Numerous sophisticated genetic methods have been developed for the zebrafish, but very little is known about its learning & memory characteristics. Thus, mechanistic analysis of these complex processes has not been possible. The goal of our proposal is to fill this gap, and make the behavioral pillar of the behavior genetics bridge as strong as its genetics pillar is. Ultimately, our studies with zebrafish will answer many questions about how memory is formed, stored and recalled, questions fundamentally important to our every day life.