A genetically tractable model of noxious cold detection in Drosophila larvae. Heather Turner¹, Christian Landry², Michael Galko¹. 1) Biochemistry and Molecular Bio, MD Anderson, Houston, TX; 2) ProDev Engineering, Houston, TX.

   An organisms comfort and even its survival depends on the ability to detect and avoid noxious thermal stimuli thus preventing tissue damage. In some disease states, patients cannot perceive or experience painful and maladaptive perception of innocuous cold and heat. Currently, our understanding of the basic biology of noxious cold perception is gravely minimal. Our goal is to determine the genetic basis for noxious cold perception using the genetically tractable Drosophila model. We have developed a novel cold probe that allows focal application of a defined noxious cold stimulus (3-15 ºC), and found that Drosophila larvae produce a mutually exclusive set of primary reactive behaviors, distinct from the previously described aversive corkscrew behavior seen in response to a high temperature probe. These behaviors include a tail raise (TR) of approximately 45-90, a combined head and tail raise (HT) of 45-90, and a full-body scrunching (SC) behavior. Below 12º C, the resulting behaviors occur in approximately 60% of larvae, and are consistent and reproducible. We probed 13 transient receptor potential (TRP) whole animal mutants to determine the possible contributions of each of the TRP channels on producing the cold-specific behaviors. Notably, we found that two mutants previously reported to affect perception of noxious heat, pyrexia and dTRPA1, both show an increase in one of our observed behaviors and a decrease in another. Alternatively, brivido mutants, recently reported to affect ambient cold preference, display exactly the opposite phenotype. Furthermore we found that the peripheral multidendritic (MD) sensory neurons that innervate the Drosophila epidermis play a significant role in producing these behaviors. Surprisingly, however, the class 4 nociceptive MD sensory neurons, which are required for noxious heat and mechanical sensation, are not required for producing cold evoked behaviors. Taken together, our unique tool and assay should allow us to uncover the cellular and molecular/genetic basis of noxious cold perception in Drosophila.