Independent insulin signaling modulators govern hot avoidance under different feeding states

Abstract

Thermosensation is critical for the survival of animals. However, mechanisms through which nutritional status modulates thermosensation remain unclear. Herein, we showed that hungry Drosophila exhibit a strong hot avoidance behavior (HAB) compared to food-sated flies. We identified that hot stimulus increases the activity of α′β′ mushroom body neurons (MBns), with weak activity in the sated state and strong activity in the hungry state. Furthermore, we showed that α′β′ MBn receives the same level of hot input from the mALT projection neurons via cholinergic transmission in sated and hungry states. Differences in α′β′ MBn activity between food-sated and hungry flies following heat stimuli are regulated by distinct Drosophila insulin-like peptides (Dilps). Dilp2 is secreted by insulin-producing cells (IPCs) and regulates HAB during satiety, whereas Dilp6 is secreted by the fat body and regulates HAB during the hungry state. We observed that Dilp2 induces PI3K/AKT signaling, whereas Dilp6 induces Ras/ERK signaling in α′β′ MBn to regulate HAB in different feeding conditions. Finally, we showed that the 2 α′β′-related MB output neurons (MBONs), MBON-α′3 and MBON-β′1, are necessary for the output of integrated hot avoidance information from α′β′ MBn. Our results demonstrate the presence of dual insulin modulation pathways in α′β′ MBn, which are important for suitable behavioral responses in Drosophila during thermoregulation under different feeding states.

Thermosensation and Temperature Preference: From Molecules to Neuronal Circuits in Drosophila

“…Behavioral assays revealed that hungry flies exhibit a strong HAB but not cold-avoidance behavior compared to sated flies. The authors also showed that MBn activity is critical for HAB, and α β MBn is required for HAB in both sated and hungry states, while αβ and γ MBn are required for HAB only during the sated state [65]. Furthermore, the authors showed that Dilp2 is secreted from IPCs, which induces the PI3K/AKT signaling in α β MBn that strongly suppresses the heat response in sated flies.…”

“…Chiang et al recently demonstrated the relationship between satiety/hunger and temperature signals within MB-based neuronal circuits [65] (Figure 3B). The authors found that the feeding state significantly affects hot-avoidance behavior (HAB) in Drosophila.…”

“…Three minutes after the flies are placed in the arena, they seek a comfortable temperature environment through temperature avoidance. Flies determine their Tp by comparing a series of experimental temperatures with a reference temperature (25 • C) [65]. (D) The temperature gradient device contains an aluminum plate, which is equipped with an array of thermoelectric chips at one side for the cold source and another array of thermoelectric chips at the other side for the hot source.…”

“…Two neuronal circuits modulate Tp in Drosophila under different feeding conditions. One is AC-based and the other is an MB-based neuronal circuit [65,97]. Umezaki et al found that flies prefer low temperatures during the hunger state [97].…”