Independent insulin signaling modulators govern hot avoidance under different feeding states

PLoS Biol. 2023 Oct 17;21(10):e3002332. doi: 10.1371/journal.pbio.3002332. eCollection 2023 Oct.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drosophila / metabolism
  • Drosophila Proteins* / genetics
  • Drosophila Proteins* / metabolism
  • Drosophila melanogaster / metabolism
  • Insulin / metabolism
  • Mushroom Bodies / physiology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Signal Transduction

Substances

  • Drosophila Proteins
  • Insulin
  • Phosphatidylinositol 3-Kinases
  • ILP2 protein, Drosophila
  • Ilp6 protein, Drosophila

Grants and funding

This work was supported by grants from the National Science and Technology Council (112-2311-B-182-002-MY3 and 109-2326-B-182-001-MY3) to C-LW, Chang Gung Memorial Hospital (CMRPD1M0301-3, CMRPD1M0761-3, and BMRPC75) to C-LW. The funders had no role in the study design, data collection and analysis, decision to publish, or manuscript preparation.