%0 Journal Article %A John M. Tauber %A Elizabeth Brown %A Yuanyuan Li %A Maria E. Yurgel %A Pavel Masek %A Alex C. Keene %T A subset of sweet-sensing neurons identified by IR56d are necessaryand sufficient for fatty acid taste %D 2017 %R 10.1101/174623 %J bioRxiv %P 174623 %X Fat represents a calorically potent food source that yields approximately twice the amount of energy as carbohydrates or proteins per unit of mass. The highly palatable taste of FAs promotes food consumption, activates reward circuitry, and is thought to contribute to hedonic feeding underlying many metabolism-related disorders. Despite a role in the etiology of metabolic diseases, little is known about how dietary fats are detected by the gustatory system to promote feeding. Previously, we showed that a broad population of sugar-sensitive taste neurons expressing Gustatory Receptor 64f (Gr64f), is required for reflexive feeding responses to both FAs and sugars. Here, we report a genetic silencing screen to identify specific populations of taste neurons that mediate fatty acid taste. We find neurons identified by expression of Ionotropic Receptor 56d (IR56d) are necessary and sufficient for reflexive feeding response to FAs. Functional imaging reveals that IR56d-expressing neurons are responsive to short- and medium-chain FAs. Silencing IR56d neurons selectively abolishes fatty acid taste, while their activation is sufficient to drive feeding responses. Analysis of co-expression with Gr64f identifies two subpopulations of IR56d-expressing neurons. While physiological imaging reveals that both populations are responsive to FAs, IR56d/Gr64f neurons are activated by medium-chain FAs and are sufficient for reflexive feeding responses to FA. Moreover, flies can discriminate between sugar and FAs in an aversive taste memory assay, indicating that FA taste is a unique modality in Drosophila. Taken together, these findings localize fatty acid taste within the Drosophila gustatory center and provide an opportunity to investigate discrimination between different categories of appetitive tastants.Authors Summary Fat represents a calorically potent food source that yields approximately twice the amount of energy as carbohydrates or proteins per unit of mass. Dietary lipids are comprised of both triacylglycerides and FAs, and growing evidence suggests that it is the free FAs that are detected by the gustatory system. The highly palatable taste of FAs promotes food consumption, activates reward centers in mammals, and is thought to contribute to hedonic feeding that underlies many metabolism-related disorders. Despite a role in the etiology of metabolic diseases, little is known about how dietary fats are detected by the gustatory system to promote feeding. We have identified a subset of sugar-sensing neurons in the fly that also respond to medium-chain FAs and are necessary and sufficient for behavioral responses to FAs. Further, we find that despite being sensed by shared neuron populations, flies can differentiate between the taste of sugar and FAs, fortifying the notion that FAs and sugar represent distinct taste modalities in flies. %U https://www.biorxiv.org/content/biorxiv/early/2017/08/10/174623.full.pdf