Abstract
Detection and discernment of disparate environmental stimuli are fundamental processes of living organisms. The ability to respond and adjust behavior according to their external or internal cues is termed plasticity. In particular, the sense of smell, or olfaction, is critical as our environment is brimming with chemical information. The valence of an odor can be influenced by many different factors, such as context, past experiences, and physiological state. Our understanding of the molecular underpinnings of context-dependent olfactory plasticity remains fragmented. Our lab has previously employed the microscopic nematode Caenorhabditis elegans to uncover a subset of molecules that regulate a context-dependent olfactory behavioral switch in the asymmetric AWC neuron pair. Worms are typically attracted to the bacterially produced odor 1-hexanol. However, this attraction reverts to aversion in the presence of a low uniform concentration (saturating) of another attractive odor, isoamyl alcohol (IAA). This context-dependent reversal is directed by both AWCOFF+ON neurons, which also switches its response sign. In the presence of only hexanol, the receptor guanylyl cyclase (rGC) ODR-1 is required to mediate attraction. However, this rGC is dispensable under saturating IAA (sIAA) conditions. I identify a rGC, GCY-12, which mediates the aversion to hexanol under sIAA conditions only in the AWCOFF neuron. In gcy-12 mutants the AWCOFF neuron is inhibited whereas the AWCON neuron is activated, as are both AWCOFF+ON neurons in wild-type animals. This results in apathy of gcy-12 mutants to a point source of hexanol under sIAA. However, cell-specific knockout of gcy-12 only in AWCOFF is not sufficient to recapitulate the indifference exhibited by gcy-12 null mutants. Only when gcy-12 is disrupted in both AWCOFF+ON neurons, animals are indifferent to hexanol under sIAA conditions. Both the Gα protein ODR-3 and cyclic nucleotide-gated channel TAX-2/TAX-4 were previously identified in wild-type animals as necessary for the aversion to hexanol under sIAA conditions. To uncover additional molecules in this odor transductionpathway, I performed a forward genetic behavioral screen. Following subsequent characterization and whole-genome sequencing analysis, I identified multiple candidates. The findings of this thesis help to further describe the neuronal and molecular basis for context-dependent olfactory adaptation.