Artificial sweeteners differentially activate sweet and bitter gustatory neurons in Drosophila

Artificial sweeteners are highly sweet, non-nutritive compounds that have become increasingly popular over recent decades despite research suggesting that their consumption has unintended consequences. Specifically, there is evidence suggesting that some of these chemicals interact with bitter taste receptors, implying that sweeteners likely generate complex chemosensory signals. Here, we report the basic sensory characteristics of sweeteners in Drosophila, a common model system used to study the impacts of diet, and find that all noncaloric sweeteners inhibited appetitive feeding responses at higher concentrations. At a cellular level, we found that sucralose and rebaudioside A co-activated sweet and bitter gustatory receptor neurons (GRNs), two populations that reciprocally impact feeding behavior, while aspartame only activated bitter cells. We assessed the behavioral impacts of sweet and bitter co-activation and found that low concentrations of sucralose signal appetitive feeding while high concentrations signal feeding aversion. Finally, silencing bitter GRNs reduced the aversive signal elicited by high concentrations of sucralose and significantly increased sucralose feeding behaviors. Together, we conclude that artificial sweeteners generate a gustatory signal that is more complex than "sweetness" alone, and this bitter co-activation has behaviorally relevant effects on feeding that may help flies flexibly respond to these unique compounds.