TRPA1 mediates sensation of the rate of temperature change in Drosophila larvae
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Avoidance of noxious ambient heat is crucial for animal survival. An important class of molecules that contributes to thermosensation is Transient Receptor Potential channels (thermoTRPs). ThermoTRPs are activated directly or indirectly by changes in temperatures, enabling animals to respond behaviorally to temperature fluctuations in the environment. The founding thermoTRP, mouse TRPV1, is activated by temperature higher than 42°C, and is required for avoidance of noxious heat. Other mammalian thermoTRPs are activated with different thresholds, such as mouse TRPM8 and TRPA1, which are activated directly by temperatures below ~23°C and ~17°C, respectively. The contribution of TRPs to thermosensation is evolutionarily conserved, and is well-documented in the invertebrate model organisms: C. elegans and Drosophila melanogaster. In Drosophila larvae, noxious heat is detected through direct activation of three TRPA channels: Painless, Pyrexia and TRPA1. The TRPA1 channel also enables larvae to sense small deviations above the preferred temperature. In the comfortable range, this fine thermal detection occurs through indirect activation of TRPA1 via a rhodopsin-dependent thermosensory signaling cascade. This signaling cascade may serve to lower the threshold for direct activation of TRPA1. The extensive studies on thermoTRPs in model organisms have contributed greatly to the theme that warm or hot temperatures of different thresholds are sensed by direct activation of TRP channels. However, a long-known but poorly understood phenomenon is that the rate of temperature change, rather than just the temperature threshold can affect the nociceptive response. Classic experiments on frogs performed more than 130 years ago demonstrated their high sensitivity and escape response to fast rises in heat, and indifference to slow increases in temperature. Stronger nociceptive reactions to fast temperature rises have been documented throughout the animal kingdom, in organisms as diverse as worms and humans. However, the mechanism underlying temperature rate detection is not clear. To explore the mechanism through which an animal responds differentially to slow and fast elevations in temperature, we developed Drosophila larvae as an animal model. We found that if we challenged larvae with a rapid temperature rise, a very high proportion of the animals exhibited nociceptive rolling behavior. However, if the temperature increase was gradual, the percentage of larvae that rolled was much lower, even after we exceeded temperatures that induced robust nociceptive avoidance after a fast temperature increase. We found one of the TRPA1 isoforms was the key rate-sensor, and was required for neurons in the brain to respond to the rate of temperature increase, rather than just the temperature threshold. Our results indicate that larvae use a TRPA1-dependent rate-sensing mechanism to safeguard the brain from exposure to noxious heat.