The GPI-anchored Ly6 protein Belly roll regulates Drosophila melanogaster escape behaviors by modulating the excitability of nociceptive peptidergic interneurons

Appropriate modulation of escape behaviors in response to potentially damaging stimuli is essential for survival. Although nociceptive circuitry has been studied, it is poorly understood how genetic contexts affect the relevant escape responses. Using an unbiased genome-wide association analysis, we identified a Ly6/-neurotoxin family protein, Belly roll (Bero), which negatively regulates Drosophila nociceptive escape behavior. We show that Bero is expressed in abdominal leucokinin-producing neurons (ABLK neurons) and bero knockdown in ABLK neurons resulted in enhanced escape behavior. Furthermore, we demonstrated that ABLK neurons responded to the activation of nociceptors and initiated the behavior. Notably, bero knockdown reduced the persistent neuronal activity and increased the evoked nociceptive responses in ABLK neurons. Our findings reveal that Bero modulates an escape response by regulating distinct neuronal activities in ABLK neurons.