Fig. 8. A schematic model of presynaptic inhibition of C4da and sugar signaling in SDGs.

a Presynaptic inhibition by SDGs via GABA signaling. Noxious stimuli first activate the peripheral C4da neurons, followed by subsequent activation of downstream secondary neurons that trigger the onset of larval rolling. During this process of nociceptive information relay, SDGs become activated and in turn send GABAergic inhibitory inputs to C4da neurons via GABA_B-Rs. This SDGs-mediated negative feedback induces rolling termination with a time lag, which enables behavior transition for efficient escape from danger. b SDGs mediate refeeding-dependent nociceptive suppression via insulin/InR signaling. Ingestion of nutritional sugar stimulates the metabolic neuronal system in the central brain, comprising the glucose-sensing CN neurons and insulin-producing cells (IPCs). Neuronal activities in SDGs, of which cell bodies are located at the SEZ brain region, are subsequently potentiated through the insulin/InR axis. The heightened responsiveness of SDGs enhances the descending inhibitory signals sent to C4da neurons, tipping the balance towards escape termination and feeding prioritization.