Modality-specific sensory integration and neuropeptide-mediated feedback facilitate mechano-nociceptive behavior in Drosophila

Nociception is an evolutionary conserved mechanism to encode and process harmful environmental stimuli. Like most animals, Drosophila larvae respond to a variety of nociceptive stimuli, including noxious touch and temperature, with a stereotyped escape response through activation of multimodal nociceptors. How behavioral responses to these different modalities are processed and integrated by the downstream network remains poorly understood. By combining transsynaptic labeling, ultrastructural analysis, calcium imaging, optogenetic and behavioral analyses, we uncovered a circuit specific for mechano- but not thermo-nociception. Interestingly, integration of mechanosensory input from innocuous and nociceptive sensory neurons is required for robust mechano-nociceptive responses. We further show that neurons integrating mechanosensory input facilitate primary nociceptive output via releasing short Neuropeptide F (sNPF), the Drosophila Neuropeptide Y (NPY) homolog. Our findings unveil how integration of somatosensory input and neuropeptide-mediated modulation can produce robust modality-specific escape behavior.