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 melanogaster larvae generate a curling and rolling response. Rover and sitter allelic variants of the Drosophila foraging (for) gene differ in parasitoid wasp susceptibility, suggesting a link between for and nociception. By optogenetically activating cells associated with each of for’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. The for null mutants display impaired responses to thermal nociception, which are rescued by restoring for expression in pr1 cells. Conversely, knockdown of for in pr1 cells phenocopies the for null 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 of for in larval nociceptive behavior. This function is specific to for pr1 neurons in the VNC, guiding a developmentally plastic escape response circuit.

痛苦或威胁性经历会触发由伤害性神经元回路引导的逃避反应。尽管该电路的某些组成部分在动物中是已知的并且是保守的，但是在遗传和发育水平上如何调节该电路却是未知的。为了逃避诸如类寄生蜂的攻击等有害刺激，果蝇果蝇幼虫会产生卷曲和滚动反应。果蝇觅食（for）基因的漫游者和保姆等位基因变体的寄生蜂黄蜂敏感性不同，这表明for和伤害感受之间存在联系。通过optogenetically激活与每一个相关联的细胞为的启动子（pr1-pr4），我们显示pr1细胞调节幼虫逃逸行为。根据寄生虫黄蜂易感性的漫游者和保姆差异，我们发现漫游者相对于保姆具有更高的pr1表达和对伤害感受的敏感性。的用于无效突变体显示受损的响应于热伤害感受，这是通过恢复救出为PR1中细胞中的表达。相反，击倒了在PR1细胞phenocopies的对空突变体。为了深入了解这种应答的潜在电路，我们使用了交叉途径和跨突触伙伴（GRASP）的活动依赖的GFP重构，以显示伤害性应答需要腹神经索（VNC）中的pr1细胞，而多树突状感觉伤害感受性神经元突触到VNC中的pr1神经元上。最后，我们表明在开发过程中激活pr1电路会抑制逃逸响应。我们的数据证明了for在幼虫伤害行为中的作用。此功能是特定于用于在VNC PR1神经元，引导发育塑料逃逸响应电路。