How the Fly Youth Chill: The Molecular Biology, Ecology, and Evolution of Cold Nociception in Drosophila and Subsequent Studies of the Evolution of TRP Channels

The ability to detect and respond to noxious, potentially harmful stimuli—a process known as nociception—is inarguably important for organismal survival. Thermal environment plays a particularly important role in insect ecology and evolution, yet little is known concerning how insects might sense and respond to cold. In Drosophila melanogaster (fruit fly) larvae, temperatures below 10°C drive a robust contractile behavior of unknown function, which is under the control of segmentally repeated Class III (CIII) sensory neurons. It has been previously shown that CIII cold sensing is dependent on Transient Receptor Potential (TRP) channels, and that CIII neurons also encode innocuous touch, but mechanisms underpinning CIII sensory multimodality and cold discrimination are unknown. Here, I give an account of several complementary studies which seek to uncover the ecological role of cold nociception, the mechanisms by which cold nociceptors discriminately encode cold, and whether or not Drosophila larvae have the ability to sense the “cooling agents” and TRP-agonists menthol and icilin. The results of these studies demonstrate that: (1) Drosophila cold nociceptors function in cold acclimation, the physiological mechanism by which insects adapt to seasonal changes in temperature; (2) Drosophila cold nociceptors discriminately encode cold using excitatory chloride currents, which can be leveraged to generate cold-hypersensitive larvae; and (3) Drosophila larvae perform TRP-dependent rolling behaviors in response to menthol. Moreover, I describe a set of bioinformatic and phylogenetic analyses seeking to understand the evolution of TRP channels; here, I describe how amino acids critical to TRPM-menthol binding are conserved across animal taxa, and outline the discovery of an ancient and previously unknown TRP family—TRP Soromelastatin (TRPS)—which is notably absent in vertebrates and insects, among others