Mutational Analyses of Learning and Memory

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Our goal is to use the power and specificity of modern mutational molecular genetics to reveal the component processes of learning and memory. Our research employs the best-understood multicellular organism (the worm C. elegans) - the first to have a completely sequenced genome and a fully mapped neural connectome. Our past work has characterized associative learning and memory in C. elegans, using tastes and smells as conditioned stimuli and the presence or absence of food as unconditioned stimuli. Screens of mutant worms have revealed novel genes involved in worm learning and memory. For example, one novel learning mutation discovered (lrn-2) was cloned and shown to be a mutation specifically in scd-2, a receptor tyrosine kinase. Most surprising, wild type scd-2 is required in one interneuron (AIA) for the integration of two sensory stimuli to control behaviour but in a separate neuron (NSM) for longer-term associative memory. Moreover, we have demonstrated higher order associative learning processes in worms (Kamin blocking and occasion setting) that some might have imagined were present only in more complex animals. Indeed, our studies of worm mutants have revealed that Kamin blocking of associative learning may be due to interference with memory recall rather than memory storage. In our most robust assay for learning and memory, a single pairing of the smell of benzaldehyde and the absence of bacterial food produces a learned avoidance of the normally preferred benzaldehyde; a memory which then lasts for a few hours. We propose to focus on this assay in order to reveal the specific neurons and molecules mediating the effects of the conditioned stimulus (Objective 1), the unconditioned stimulus (Objective 2), and their association and subsequent storage of the memory produced (Objective 3).