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Chemosensory systems are critical for evaluating the caloric value and potential toxicity of food. While animals can discriminate between thousands of odors, much less is known about the discriminative capabilities of taste systems. Fats and sugars represent calorically potent and attractive food sources that contribute to hedonic feeding. Despite the differences in nutritional value between fats and sugars, the ability of the taste system to discriminate between different rewarding tastants is thought to be limited. In  Drosophila , taste neurons expressing the ionotropic receptor 56d ( IR56d ) are required for reflexive behavioral responses to the medium-chain fatty acid, hexanoic acid. Here, we tested whether flies can discriminate between different classes of fatty acids using an aversive memory assay. Our results indicate that flies are able to discriminate medium-chain fatty acids from both short- and long-chain fatty acids, but not from other medium-chain fatty acids. While  IR56d  neurons are broadly responsive to short-, medium-, and long-chain fatty acids, genetic deletion of  IR56d  selectively disrupts response to medium-chain fatty acids. Further,  IR56d+ GR64f + neurons are necessary for proboscis extension response (PER) to medium-chain fatty acids, but both  IR56d  and  GR64f  neurons are dispensable for PER to short- and long-chain fatty acids, indicating the involvement of one or more other classes of neurons. Together, these findings reveal that  IR56d  is selectively required for medium-chain fatty acid taste, and discrimination of fatty acids occurs through differential receptor activation in shared populations of neurons. Our study uncovers a capacity for the taste system to encode tastant identity within a taste category.

Ir56d -dependent fatty acid responses in Drosophila uncover taste discrimination between different classes of fatty acids