Cold sensing by a glutamate receptor drives avoidance behavior in Drosophila larvae

The ability to sense and avoid noxious environments is essential for animal survival. While the mechanisms of heat and cool sensation are well studied, those underlying the sensation of cold are relatively less understood. Here, we use Drosophila larvae as a model to investigate how animals sense and avoid cold temperatures. By implementing custom-built thermoelectric devices capable of delivering rapid and precise thermal stimuli, we find that cold delivered to the larval head evokes robust escape behavioral responses. We identify anterior C3da (aC3da), a group of head-located cold-sensitive neurons, as necessary and sufficient for such avoidance responses. We further demonstrate that the kainate-type glutamate receptor Clumsy acts as a novel cold sensor required for head cold sensitivity. Knockdown of Clumsy in head cold-sensing neurons suppresses their cold sensitivity. Heterologous expression of Clumsy confers cold sensitivity. Our results show that Drosophila larvae have evolved the capacity to detect and avoid cold temperatures through a previously uncharacterized cold-sensing mechanism.