Genetic Dissection of a Complex Behavioral Phenotype

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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.