Genetic Dissection of a Complex Behavioral Phenotype

在这个提议中，我描述了一些研究，以加深我们对最简单的学习形式——习惯化的生物学机制的理解。习惯化是学习忽略那些不能预测其他任何事情的刺激。它们是可以被安全地忽略的刺激。习惯化使生物体能够忽略环境中不重要的刺激，并使它们能够关注那些能够预测生物相关刺激的刺激，比如食物或危险。尽管在所有被研究的生物中，居住的行为规则似乎都是相同的，但令人惊讶的是，人们对任何生物的习惯化机制知之甚少。我的研究重点是试图了解一种微小的蠕虫——秀丽隐杆线虫（C. elegans）的生物学基础。我们使用这种动物的原因是，秀丽隐杆线虫只有302个脑细胞，而不是人类拥有的数万亿个脑细胞。在这种简单的动物中，我们知道每个脑细胞是做什么的，以及它与什么相连。此外，我们已经对这种蠕虫的基因组进行了测序，我们有大量已知基因的突变可以研究。（我用的比喻是，研究秀丽隐杆线虫而不是哺乳动物的学习能力，就像用手电筒而不是电脑来理解电学的基本原理。）我们已经确定了一些改变机械感觉刺激习惯的基因。这个提议是为了研究我们发现的突变，以确定在这种简单的学习形式中起作用的基因途径。我们相信，我们在秀丽隐杆线虫中发现的机制将类似于像我们自己这样更复杂的大脑所使用的机制，并且通过了解微观蠕虫的习惯化，我们将深入了解我们自己的大脑是如何学习和记忆的。＊＊＊＊

In this proposal I describe research to deepen our understanding of the biological mechanisms of the simplest form of learning, habituation. Habituation is learning to ignore stimuli that don't predict anything else. They are stimuli that can safely be ignored. Habituation allows organisms to ignore unimportant stimuli in the environment and allows them to attend to stimuli that do predict biologically relevant stimuli like food or danger. Although the behavioural rules for habitation appear to be the same in all organisms studied, surprisingly little is known about the mechanism of habituation in any organism. My research has focused on trying to understand the biological basis of habitation in a microscopic worm, C. elegans. The reason we use this animal is that instead of the trillions of brain cells that humans have, C. elegans has only 302 brain cells. In this simple animal we know what is each brain cell does and what it is connected to. In addition this worm has had its genome sequenced and we have a large number of mutations in known genes that we can study. (The analogy I use is that studying learning in C. elegans rather than in mammals is like using a flashlight rather than a computer to understand basic principles of electricity.) We have identified a number of genes that alter habituation to a mechanosensory stimulus. This proposal is to investigate the mutations we have found to determine the gene pathways that play a role in this simple form of learning. We believe that the mechanisms we find in C. elegans will be similar to mechanisms used by more complex brains like our own, and that by understanding habituation in the microscopic worm we will gain insights into how our own brains learn and remember. ****