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TRPV1-Independent and Sex-Specific Capsaicin Signatures in Drosophila

ABSTRACT: The ability to sense capsaicin has been predominantly characterized in mammals through activation of the transient receptor potential vanilloid subtype 1 (TRPV1) in nociceptive neurons, yet how this compound is sensed in organisms lacking TRPV1 remains poorly understood, often leading to an overreliance on TRP-based mechanistic explanations that are contradictory and inconclusive. Here, we show that capsaicin modulates feeding behavior and activity in Drosophila melanogaster, which lacks a TRPV1 ortholog, through a mechanism involving the chemosensory system that is independent of metabolic state and the gut. Integration of single-nuclei brain transcriptomics (snRNA-seq) with bulk RNA sequencing revealed sex-specific transcriptomic reprogramming, engaging a common desensitization axis through Drosulfakinin (Dsk) in peptidergic neurons and Clk regulon-associated signatures in glial cells. Using functional genetics, we identified the gustatory system as the primary mediator of this response, involving Gr64f+ neurons and Gr64e. Together, our study defines a noncanonical, TRP-independent mechanism of capsaicin detection, revealing an alternative chemosensory framework and gives a glimpse of sex-dependent transcriptional adaptations that may shape behavioral responses.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE305959 | GEO | 2025/09/26

REPOSITORIES: GEO

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