We are studying contextual learning using C. elegans olfactory adaptation as a model. When worms are exposed to a high concentration of an attractive odorant for a prolonged period, they become insensitive to the odorant in a process termed olfactory adaptation. We have found that ethanol generates a state-dependency to adaptation: Worms exposed simultaneously to a high concentration of odorant and ethanol only demonstrate adaptation to the odorant if they are tested while being exposed to ethanol. If the worms are removed from ethanol after the training period, they no longer display adaptation to the odorant. In effect, these animals have experienced state-dependent learning. We have also found that this learning requires normal dopaminergic function. This assay provides an opportunity to study state-dependent learning using a molecular genetics approach. We have begun genetic screens to find mutations that disrupt the process, and have identified one mutation that disrupts state-dependent learning. Molecular characterization of this and other mutations will provide insight into the mechanisms of learning in C. elegans. We will also use pharmacological manipulations and existing mutants to disrupt particular neurochemical pathways to determine which are important for this learning.
