Behavioural, Optogenetic and Genetic Dissection of Simple Forms of Plasticity

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Animals live in constantly changing environments and they must change their behaviour in response to changes in the environment if they are going to survive. The simplest forms of behavioural plasticity are: sensory adaptation, habituation, dishabituation and sensitization. Sensory adaptation is when the sensory receptors stop responding to stimuli (sensory fatigue), habituation is when animals decrease responding to a repeated stimulus that does not seem to predict anything good or bad. Habituation is distinguished from adaption in two ways: 1) it can be reversed immediately after applying a strong novel or noxious stimulus, a procedure called dishabituation, and 2) habituation spontaneously recovers differently depending on the rate of stimulation during habituation; this rate is the opposite of what recovery from fatigue would predict. Sensitization is thought of as an organism-wide arousal that increases all responses after detection of an exciting or threatening stimulus. Usually, these simple processes have been studied in isolation in different organisms and some mechanistic insights have been uncovered for some of these processes in one or more organisms. The Dual Process Theory by Groves and Thompson (1970) used behavioural data from a broad range of organisms to hypothesize that habituation occurs in the local S-R circuit for the behaviour, while sensitization and dishabituation (they suggested were essentially the same process) occur organism-wide and reflect a change in the state system of the animal. One of the defining characteristics of habituation is that it is not sensory adaptation. however, is that true? There have been no systematic investigations into whether adaptation can play a role in habituation. We are using the nematode C. elegans, an animal with only 302 neurons (brain cells) for which we have a complete wiring diagram, a sequenced genome that is amenable to many cutting-edge genetic engineering tools, to understand the genes that mediate sensory adaptation, habituation, dishabituation, and sensitization. My laboratory has been studying the genetic basis of behaviour in C. elegans for more than 25 years and we have experience with the tools, the technology and knowledge of the important questions in this area to carry out this research. The overarching goal of my NSERC grant is to systematically investigate these 4 simple forms of plasticity in the genetic model organism C. elegans in order to understand the mechanisms underlying these behavioural phenomena, and understand the relationships between them in order to gain insight into how they are integrated to produce adaptive behaviour in response to changing stimulus conditions. Because these simple forms of plasticity are going on in animals all of the time, our results will also result in general principles that should be considered by all researchers studying learning and memory.