Metabolic states have a profound impact on cognitive function and our perception of the external world. Hunger launches complex and widespread changes throughout the nervous system to influence animal behavior on multiple levels. To promote feeding behavior, hunger increases the sensitivity of peripheral gustatory and olfactory neurons to sugar and food odor, respectively. Additionally, nutrient deprived animals may concomitantly suppress reproductive and other behavior as they prioritize the need to maintain energy homeostasis. However, the mechanisms by which an organism's nutritional state impacts reproductive behavior are poorly understood. Uncovering them would expand our understanding of how a single internal state can coordinate multiple behavioral modules and subprograms. The proposed experiments will be carried out in Drosophila, an organism with an anatomically simple nervous system that is amenable to molecular and genetic manipulations, optical imaging technologies, and behavioral analysis. The goal of this proposal is to determine the molecular and neural mechanisms that communicate nutritional status to mating circuits. In a published study, we established a sensitive behavioral assay to measure olfactory contribution to male mating behavior and found the Or47b olfactory sensory neurons promote mating behavior. Preliminary studies with this novel behavioral assay demonstrate that internal detection of specific nutrients and the subsequent release of a neuropeptide are both required for mating behavior. A multifaceted study employing behavioral analysis, molecular genetics and two-photon calcium imaging is proposed to investigate the following three questions. First, which population of neurons releases the neuropeptide to modulate male courtship behavior? Second, what is the locus in the Or47b circuit where hunger modulates mating behavior? Third, does neuropeptide signaling intersect with the Or47b circuit at this locus to control mating behavior? Under Dr. Wang's current mentorship and within the rich and resourceful environment provided by UCSD, I am uniquely positioned to decipher this fundamental neural mechanism. Together with a comprehensive career development plan, including establishing collaborations and continued training and education, these elements will undoubtedly facilitate my transition to independent research and allow me to become a well-established investigator in one of the world's top-research institutes.
Obesity is a complex biological problem that affects an increasingly large population of people worldwide. The work of this proposal is basic science that seeks to reveal the connection between internal nutrient sensing and olfactory information processing in the brain. Defining the action of molecular signaling from specific nutrients will create a knowledge base from which potential molecular targets can be evaluated for future therapeutic interventions.
