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; yet, how this is achieved at the behavioral, neuronal, and molecular levels is not well 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 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.