Regulation Of Foraging And Feeding Behavior By Insulin And Glucagon Signaling In Adult Drosophila

The survival and health of animals,including humans,depend on the monitoring and regulation of the state of the body's energy.Excessive energy can cause diseases such as obesity,and energy deficiency can lead to death.Animals exhibit both foraging and feeding behavior when starving.At present,a large number of studies have reported the neuro-metabolic regulation mechanisms of feeding behavior,but little research has been carried out on foraging behavior.Foraging behavior is cross-species conserved and plays a key role in guiding animal positioning and access to adequate food sources to meet their own metabolic and reproductive needs.Up to now,the study of foraging behavior mainly comes from the ecological and behavioral research in the natural environment,and its genetic and neurobiological mechanisms have great gaps.In addition,hunger is the common motivation for foraging and feeding behavior,and it is still unclear whether these two behaviors are regulated by the same neural mechanisms.In this study we established the first high-throughput and quantitative animal foraging behavior model and found that the starved adult Drosophila exhibited an increase in locomotor activity.This hyperactivity helps starved flies to find food more efficiently and is a suitable indicator for studying foraging behavior.We began with the neuropeptide system to study the neural mechanism underlying how internal energy state regulates foraging behavior.We systematically analyzed the function of all known flies' neuropeptide receptors in foraging behavior and found that the Adipokinetic hormone receptor(AKHR)was involved in the regulation of foraging behavior.AKHR was expressed in-4 neurons in the subesophageal zone.Inhibition of AKHR+neurons or decreasing the expression of AKHR or AKH caused starved flies to lose the ability to up-regulate foraging behavior.Conversely,activation of AKHR+neurons accelerated the onset of foraging behavior upon starvation.These results illustrate that AKH-AKHR signaling and AKHR+neurons were both necessary and sufficient for the regulation of foraging behavior.AKHR+neurons also expressed Drosophila insulin receptor(dInR).The satiety hormone Drosophila insulin-like peptides(DILPs)exerts a suppressive effect on starvation-induced hyperactivity via dInR signaling.Therefore,AKHR+ neurons can integrate satiety signal DILPs and starvation signal AKH,regulate the physical activity of fruit flies in real time,and ensure that flies respond quickly to the internal energy status and external food signals.In addition,AKHR neurons transmitted signals downstream by releasing neurotransmitter octopamine,which is known to have six receptors in Drosophila.Oct?2R was involved in the regulation of foraging behavior,suggesting that AKHR+neurons may regulate foraging behavior through Oct?2R+neurons.In addition,we found that AKHR and AKHR+neurons were neither necessary nor sufficient for starvation-induced food consumption,suggesting that there are multiple mechanisms in the animal's nervous system that sense hunger and trigger different behavioral outputs.This finding challenges the long-standing perception from mammalian research that the central nervous system has a single functional unit(such as the hypothalamus)that senses the energy level of the body.The main conclusions and innovations:1.Established the first high-throughput and quantitative animal foraging behavior model in Drosophila.2.Characterized the hormonal and neural regulation of foraging behavior through AHK-AKHR signaling and octopamine-Oct?2R signaling.3.Identified AKHR+neurons in the SEZ region to regulate foraging behavior by integrating satiety signal DILPs and starvation signal AKH.4.Illustrated starvation-induced foraging and feeding behaviors regulated independently via different neuropeptide systems.