AUTHOR=Kohatsu Soh , Tanabe Noriko , Yamamoto Daisuke , Isono Kunio TITLE=Which Sugar to Take and How Much to Take? Two Distinct Decisions Mediated by Separate Sensory Channels JOURNAL=Frontiers in Molecular Neuroscience VOLUME=Volume 15 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2022.895395 DOI=10.3389/fnmol.2022.895395 ISSN=1662-5099 ABSTRACT=In Drosophila melanogaster, gustatory receptor neurons (GRNs) for sugar taste coexpress various combinations of gustatory receptor (Gr) genes and are found in multiple sites on the body. To determine whether diverse sugar GRNs expressing different combinations of Grs have distinct behavioral roles, we examined the effects on feeding behavior of genetic manipulations which promote or suppress functions of GRNs that express either or both of the sugar receptor genes Gr5a (Gr5a+ GRNs) and Gr61a (Gr61a+ GRNs). Cell-population-specific overexpression of the wild-type form of Gr5a (Gr5a+) in the Gr5a mutant background revealed that Gr61a+ GRNs localized on the legs and internal mouthpart critically contribute to food choice but not to meal size decisions, while Gr5a+ GRNs, which are broadly expressed in many sugar-responsive cells across the body with an enrichment in the labella, are involved in both food choice and meal size decisions. The legs harbor two classes of Gr61a expressing GRNs, one with Gr5a expression (Gr5a+/Gr61a+ GRNs) and the other without Gr5a expression (Gr5a-/Gr61a+ GRNs). Although both of these classes of tarsal GRNs mediate the feeding preference for sugars, the Gr5a+ subset is better tuned to trehalose and the Gr5a- subset is better tuned to fructose: blocking the Gr5a+ subset reduced preference for trehalose, whereas blocking the Gr5a- subset reduced preference for fructose. These two subsets of GRNs are also different in their central projections: axons of tarsal Gr5a+/Gr61a+ GRNs terminate exclusively in the ventral nerve cord, while some axons of tarsal Gr5a-/Gr61a+ GRNs ascend through the cervical connectives to terminate in the subesophageal ganglion. We propose that tarsal Gr5a+/Gr61a+ GRNs and Gr5a-/Gr61a+ GRNs represent functionally distinct sensory pathways that function differently in food preference and meal-size decisions.