The overall goal of this research plan is to improve understanding about mammalian bile acid chemosignaling through the accessory olfactory system (AOS). Bile acids ? well known regulators of fat digestion and metabolism ? also serve as external chemosignals for the AOS. In most mammals, the AOS directly influences brain regions that control anxiety and social behaviors, and understanding this brain pathway is likely to provide insights into mammalian sexual/reproductive drive, social anxiety, and moods. New knowledge about AOS function may be utilized to help control rodent populations, including those that harbor harmful microorganisms. The mechanisms of peripheral bile acid sensation, the mechanisms of bile acid information processing in the brain, and the behavioral impacts of bile acids are currently unknown. The proposed research will combine new calcium imaging techniques with transcriptome analysis to identify the peripheral AOS receptor(s) sensitive to bile acids. Other proposed experiments will investigate network properties in accessory olfactory bulb (AOB), where bile acid and other steroid information is integrated. Finally, behavioral assessment will be coupled to brain-wide immediate early gene mapping to determine the overall impacts of bile acid chemosensation on brain activity and behavior. The proposed research will investigate these topics in order to improve understanding of this important class of mammalian chemosignals. The results of the proposed experiments will ultimately benefit human health by linking mammalian gut physiology to brain function.
The proposed research will investigate mammalian chemosensory detection, processing, and behavioral impact of bile acids, cholesterol derivatives that are essential for fat and vitamin absorption and are excreted in feces. The specific complement of bile acids in feces varies with sex, species, and gut microbes, and mice and other disease-carrying rodents may respond to these chemosensory cues with changes in social and reproductive behaviors, but the neural mechanisms by which this may occur are not understood. Discovering the mechanisms of mammalian bile acid detection, identifying how bile acid information is processed by neural circuits, and learning how bile acids influence mouse behavior will improve our overall understanding of the mammalian brain, and may identify new strategies for managing rodent populations.
