Neuromodulation of Sex-Specific Pheromone-Mediated Behaviors

The ability of organisms to sense – and properly respond to – their environment is crucial to their survival. Higher organisms communicate with conspecifics to ensure the survival of the species. Nematodes, such as the roundworm Caenorhabditis elegans, are ubiquitous across all biomes, and rely on chemical communication to convey information with one another. The small molecules they utilize in this communication are called ascarosides. These modular pheromones are employed by all taxa, ranging from Caenorhabditis to Ascaris. The ascaroside, ascr#8, is release by hermaphroditic C. elegans to attract potential mates. Previous work has shown that a class of male specific neurons are required for sensation of this pheromone. Here, we show that these neurons initiate a neural circuit modulated by the FMRFamide-like neuropeptide, flp-3. This neuropeptide is sensed by a set of G protein-coupled receptors (GPCRs), NPR-10 and FRPR-16. Together, these components determine the behavioral valence of males to ascr#8. Within the male-specific sensory neurons, the CEM, we show that another group of GPCRs sense the ascr#8. Two of these receptors, DMSR-12 and SRW-97, are expressed in the cilia, suggesting their involvement in direct sensation of the cue. As a targeted approach to identifying and confirming receptors for ascr#8, we have developed a bioactive photoaffinity probe. We have also confirmed that the ability of ascr#8 to attract males is conserved across the genus. Together, these studies coalesce to deepen our understanding of sex-specific chemosensation and neuronal processing. These results can be used to better understand the defects that are seen in neurodegenerative diseases – many of which exhibit sex-specific defects in neuronal processing