Drosophila melanogaster foragingregulates a nociceptive-like escape behavior through a developmentally plastic sensory circuit

Painful or threatening experiences trigger escape responses that are guided by nociceptive neuronal circuitry. Although some components of this circuitry are known and conserved across animals, how this circuitry is regulated at the genetic and developmental levels is mostly unknown. To escape noxious stimuli, such as parasitoid wasp attacks,Drosophila melanogasterlarvae generate a curling and rolling response. Rover and sitter allelic variants of theDrosophila foraging(for) gene differ in parasitoid wasp susceptibility, suggesting a link betweenforand nociception. By optogenetically activating cells associated with each offor’s promoters (pr1–pr4), we show that pr1 cells regulate larval escape behavior. In accordance with rover and sitter differences in parasitoid wasp susceptibility, we found that rovers have higher pr1 expression and increased sensitivity to nociception relative to sitters. Thefornull mutants display impaired responses to thermal nociception, which are rescued by restoringforexpression in pr1 cells. Conversely, knockdown offorin pr1 cells phenocopies thefornull mutant. To gain insight into the circuitry underlying this response, we used an intersectional approach and activity-dependent GFP reconstitution across synaptic partners (GRASP) to show that pr1 cells in the ventral nerve cord (VNC) are required for the nociceptive response, and that multidendritic sensory nociceptive neurons synapse onto pr1 neurons in the VNC. Finally, we show that activation of the pr1 circuit during development suppresses the escape response. Our data demonstrate a role offorin larval nociceptive behavior. This function is specific toforpr1 neurons in the VNC, guiding a developmentally plastic escape response circuit.