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A Taste For Amino Acids: Investigating The Molecular Mechanisms That Mediate Amino Acid-Guided Behaviors In Drosophila Melanogaster
Guillemin, Jacqueline A.
Guillemin, Jacqueline A.
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Abstract
Taste, a shared yet diverse sense found across the animal kingdom that communicates information about the molecular makeup of food to the central nervous system. Chemicals in food signal nutritional value and potential toxicity; therefore, they must be accurately detected to coordinate appropriate responses. A key dietary nutrient that must be recognized is protein, and its constituent parts, amino acids (AAs). Protein and AA intake must be tightly regulated, as they are essential nutrients but can also have detrimental effects on health if overconsumed. Investigations into the taste cells and receptors responsible for detecting AAs in mammals have produced a variety of results, with some mammals tasting all proteinogenic AAs with the canonical “umami” receptor, and others identifying individual AAs through multiple receptors and cell types. Overall, previous research suggests that these chemicals may act through multiple sensory pathways to regulate AA feeding; however, direct evidence on how the nervous system encodes AA taste to drive appropriate behavioral responses remains an active area of investigation. The fruit fly, Drosophila melanogaster, is an ideal model for understanding sensory neurobiology due to its simple nervous system, an analogous tongue-like structure—the labellum—that responds to similar taste cues as mammals, the availability of a whole-brain connectome, extensive genetic tools, and robust behavioral assays. Additionally, research in Drosophila can allow for a deeper understanding of diverse insect chemosensory systems, which are utilized not only for feeding, but also for mate identification and oviposition. The neurobiological coding of AAs in the fruit fly is an active field of study, with the identification of some cells and receptors that are necessary for responding to single AAs. Notably, animals do not naturally encounter single AAs in their diet; rather, they encounter complex mixtures. Using in vivo calcium imaging, we identified three taste cell populations that respond to a mixture of AAs and determined that one mediates appetitive feeding and two guide aversive feeding behaviors through a variety of chemoreceptors. We further investigated a poorly understood cell type involved in AA taste coding, which expresses Ionotropic Receptor 94e (IR94e), to elucidate whether there is a unique ligand for this population or any additional behavioral roles. We employed optogenetic and chemogenetic assays, whole-brain connectomic analysis, and in vivo calcium imaging to discover that the IR94e cells and receptors are integral for the identification of glutamate solutions and specifically function as a behavioral switch between feeding and egg laying. These observations indicated that IR94e could be functionally important for the survival and reproductive success of the fly. To investigate this directly, we performed multiple behavioral and physiological experiments, finding that the loss of IR94e in Drosophila melanogaster elicits a physiological change in activity levels and fat storage, resulting in a decrease in survival. The results obtained throughout these studies have highlighted the importance of AA taste cues in multiple behaviors and overall health in Drosophila melanogaster. This work establishes a complex, combinatorial code for AA taste in the nervous system and highlights the widespread impacts that a single chemosensory receptor can have on physiology. This basic neurobiological research has potential applications in animal health, enabling a deeper understanding of AA feeding decisions, and could be utilized to respond to insect pest species that target crops.
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2025
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