Gustatory-mediated Neuronal Circuits Regulate Drosophila Physiology and Longevity. Michael J. Waterson¹, Tammy P. Chan², Zachary M. Harvanek³, Ivan Ostojic⁴, Joy Alcedo^4,5, Scott D. Pletcher^1,3. 1) Cellular and Molecular Biology Graduate Program, University of Michigan; 2) Department of Developmental Biology, Baylor College of Medicine, Houston, TX; 3) Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI; 4) Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland; 5) Department of Biological Sciences, Wayne State University, Detroit, MI.

   The integration of environmental information within the central nervous system is crucial to the regulation of aging, yet the circuitry of this regulation remains poorly understood. D. melanogaster offers a simple, yet conserved neuronal architecture and the genetic reagents needed to tackle the difficulty of mapping neural regulatory networks. Previous work has provided strong evidence for chemosensory inputs in modulating longevity. We have thus focused on one such set of these signals - gustatory inputs - as a model to understand this regulation.
   To determine which specific gustatory inputs regulate certain aging phenotypes, we utilized multiple genetic techniques to systematically manipulate the expression of single gustatory inputs and measured their effects on lifespan. Our work has identified three gustatory genes, representing three distinct taste modalities, as potent regulators of fly longevity.
   Our initial work in elucidating this gustatory-mediated neuronal circuitry has focused on one of these inputs, an ion channel critical for the activation of one subtype of gustatory receptor neurons. Importantly, we have found that this input can regulate nutrient homeostasis, and that lifespan extension mediated by this circuit requires two neuroendocrine signaling pathways. These data suggest a model in which gustatory signals, transduced to the CNS, modulate signaling responsible for the systemic control of metabolic homeostasis and the regulation of an organisms physiological state. The cumulative effects of these corresponding physiological changes, in turn, contribute to the rate at which the animal ages.