Associative Learning in Zebrafish

学习和记忆是大脑重要而复杂的功能。虽然在学习和记忆背后的心理、神经生物学和分子机制方面已经有了重大发现，但大多数科学家都认为，我们才刚刚开始触及表面。这一研究领域的绝大多数研究都是在实验室啮齿动物身上进行的。然而，一种新的实验室物种——斑马鱼，可能会提供一些优势，并可能让我们更快地发现学习和记忆的基本方面。在这里，我们提出了一个程序来分析学习和记忆使用斑马鱼。具体来说，我们将首先研究斑马鱼学习任务的动机。没有适当的激励（奖励或惩罚），学习就不会发生。斑马鱼是学习和记忆研究的新手，我们将研究如何在食物奖励任务中避免快速饱足。此外，我们将优化计算机呈现的社会线索，这些线索高度激励斑马鱼，这是一种社会物种。我们也将探讨自然环境刺激的动机价值。其次，斑马鱼记忆研究中最大的问题是人类处理引起的压力。我们将开发基于家庭水箱的学习任务来避免这种压力，这一发展将大大提高人们研究斑马鱼复杂学习过程的能力。我们的第三个目标是描述简单和复杂形式的联想学习。复杂的形式（称为关系学习和记忆）特别有趣，因为它们与我们人类形成情景/陈述性或有意识的可回忆性记忆的方式相似。在一项开创性的研究中，我们已经证明斑马鱼可以形成关系记忆。在这里，我们将使用我们的家庭水箱范例来研究这种类型的记忆，通过实验控制一系列视觉刺激的呈现，这些视觉刺激的顺序和共现性必须由鱼学习才能获得奖励。我们的第四个目标是确定鱼记住简单和复杂记忆的时间，以及这些记忆是否容易被实验操作破坏或修改。也就是说，我们将研究斑马鱼的简单和复杂的记忆形式是如何稳定或可改变的。在5年的资助结束时，我们将了解斑马鱼学习和记忆的基本行为机制，这将对我们项目的下一阶段至关重要：分析记忆过程背后的分子和神经生物学机制。我们对我们的提议感到兴奋，因为我们已经在斑马鱼身上发现了许多进化上保守的特征，从基因的核苷酸序列到神经递质系统，再到大脑对人类药物的反应。因此，人类和斑马鱼特征之间的这些相似性表明，我们将在斑马鱼身上发现的东西将适用于各种其他脊椎动物。

Learning and memory are important and complex functions of the brain. While significant discoveries have been made about the psychological, neurobiological and molecular mechanisms underlying learning and memory, most scientists agree, we have only started to scratch the surface. The overwhelming majority of the studies in this research area have been conduced with laboratory rodents. However, a new laboratory species, the zebrafish, may offer some advantages and may allow us to discover fundamental aspects of learning and memory faster. Here, we propose a program for the analysis of learning and memory using the zebrafish. Specifically, we will first investigate what motivates zebrafish in learning tasks. Without proper motivators (reward or punishment) learning does not occur. Zebrafish is a newcomer in learning and memory research and we will investigate how to avoid fast satiation in food rewarded tasks. Also, we will optimize computer-presented social cues that highly motivate zebrafish, a social species. We will also investigate the motivational value of natural environmental stimuli. Second, the biggest issue in zebrafish memory research is human handling induced stress. We will develop home-tank based learning tasks to avoid this stress, a development that will substantially increase one's ability to study complex learning processes in the zebrafish. Our third goal is to characterize simple and complex forms of associative learning. The complex forms (called relational learning and memory) are particularly interesting as they are similar to what allows us, human beings, to form episodic/declarative or consciously recallable memories. In a pioneering study, we have shown that zebrafish could form relational memories. Here, we will study this type of memory using our home-tank paradigm with experimentally controlled presentation of a series of visual stimuli whose order and co-occurrence will have to be learned by the fish to obtain reward. Our fourth goal is to determine how long fish remember simple and complex memories and whether these memories are prone to disruption or modification by experimental manipulations. That is, we will study how stable or modifiable simple and complex forms of memories are in the zebrafish. At the end of the 5-year grant, we will have understood fundamental behavioural mechanisms of learning and memory in zebrafish, which will be crucial to the next phase of our program: the analysis of molecular and neurobiological mechanisms underlying memory processes. We are excited about our proposal because numerous evolutionarily conserved features have been identified in the zebrafish, ranging from nucleotide sequences of its genes through its neurotransmitter systems to how its brain responds to drugs developed for humans. Thus, these similarities between human and zebrafish features suggest that what we will discover with zebrafish will be translatable to a variety of other vertebrates.