Associative Learning in Zebrafish

学习和记忆是大脑的重要而复杂的功能。虽然关于学习和记忆背后的心理、神经生物学和分子机制已经有了重大发现，但大多数科学家都认为，我们才刚刚开始触及皮毛。这一研究领域的绝大多数研究都是用实验室啮齿动物进行的。然而，一种新的实验室物种斑马鱼可能会提供一些优势，可能会让我们更快地发现学习和记忆的基本方面。在这里，我们提出了一个用斑马鱼来分析学习和记忆的程序。具体地说，我们将首先调查斑马鱼在学习任务中的动机。没有适当的动机(奖励或惩罚)，学习就不会发生。斑马鱼在学习和记忆研究方面是一个新来者，我们将研究如何在食物奖励任务中避免快速饱足。此外，我们还将优化计算机呈现的社交线索，以高度激励斑马鱼这一社会性物种。我们还将调查自然环境刺激的激励价值。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，以避免这种压力，这一发展将大大提高一个人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。这种复杂的形式(称为关系学习和记忆)特别有趣，因为它们类似于我们人类形成情节/陈述性或有意识地回忆的记忆。在一项开创性的研究中，我们表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坦克范式来研究这种类型的记忆，并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有多长，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形式的记忆有多稳定或可修改。在为期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，这将对我们计划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，因为已经在斑马鱼中发现了许多进化上保守的特征，从它的基因核苷酸序列到它的神经递质系统，再到它的大脑如何对为人类开发的药物做出反应。因此，人类和斑马鱼特征之间的这些相似之处表明，我们在斑马鱼身上发现的东西将可以翻译到其他各种脊椎动物身上。

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.