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Authors: Maggie N. Benson, Nathaniel J. Himmel, Jamin M. Letcher, Akira Sakurai, Thomas R. Gray, and Daniel N. Cox

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In humans, topical application of menthol typically elicits a pleasant cooling sensation. Insects like Drosophila melanogaster, however, find menthol aversive. In chordates, the primary molecular sensors of menthol are the transient receptor potential (TRP) channels TRPA1 and TRPM8. TRP channels are highly conserved, incredibly ancient, and important in sensing both noxious and innocuous stimuli – importantly, they are key to systems underlying nociception and pain. TRPA1 and TRPM8 function in Drosophila thermosensation and noxious chemical detection, but it is unknown if TRP-mediated menthol sensing is equally ancient and/or present in insects. In order to further our understanding of insect menthol sensing and TRP evolution, we tested the hypothesis that Drosophila melanogaster senses and responds to menthol in a TRP-dependent manner. Combining a genetic and behavioral approach, we found that menthol elicits a TrpA1- and Trpm- dependent nociceptive rolling behavior in Drosophila melanogaster larvae. In vivo calcium imaging and single-unit electrophysiological recordings revealed that menthol activates Class IV sensory neurons. Moreover, class-specific RNAi knockdown of TrpA1 and Trpm resulted in reduced menthol sensitivity. Finally, phylogenetic approaches were employed in order to make inferences about the evolution of TRPM and TRPA family channels. These analyses revealed that many amino acid residues previously implicated in menthol sensing are conserved in Drosophila Trpm, but less well conserved in Drosophila TrpA1.

Our experiments reveal that, like in chordates, insects rely on TRP channels in order to detect menthol. These findings, in combination with previous discoveries concerning TRP function, demonstrate that the sensory capacity of TRP channels have origins predating the protostome-deuterostome split (~600mya).


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19 Jul 2022
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  • Event location
    • Cleveland Ballroom

  • Event date
    • 2 November 2019

  • Date submitted

    19 July 2022