A neural circuit linking two sugar sensors regulates satiety-dependent fructose drive in .

In flies, neuronal sensors detect prandial changes in circulating fructose levels and either sustain or terminate feeding, depending on internal state. Here, we describe a three-part neural circuit that imparts satiety-dependent modulation of fructose sensing. We show that dorsal fan-shaped body neurons display oscillatory calcium activity when hemolymph glucose is high and that these oscillations require glutamatergic input from SLP-AB or “Janus” neurons projecting from the protocerebrum to the asymmetric body. Suppression of activity in this circuit, either by starvation or by genetic silencing, promotes specific drive for fructose ingestion. This is achieved through neuropeptidergic signaling by tachykinin, which is released from the fan-shaped body when glycemia is high. Tachykinin, in turn, signals to Gr43a-positive fructose sensors to modulate their response to fructose. Together, our results demonstrate how a three-layer neural circuit links the detection of two sugars to produce precise satiety-dependent control of feeding behavior.