Neural basis of hunger-driven behaviour in Drosophila

Abstract

Hunger is a motivational state that drives eating and food-seeking behaviour. In a psychological sense, hunger sets the goal that guides an animal in the pursuit of food. The biological basis underlying this purposive, goal-directed nature of hunger has been under intense investigation. With its rich behavioural repertoire and genetically tractable nervous system, the fruit fly Drosophila melanogaster has emerged as an excellent model system for studying the neural basis of hunger and hunger-driven behaviour. Here, we review our current understanding of how hunger is sensed, encoded and translated into foraging and feeding behaviours in the fruit fly.

Keywords: Drosophila; feeding behaviour; food-seeking behaviour; hunger; neural circuits.

Figure 1.

Hunger and satiety signals and their interactions. The numbers on the lines indicate the references in which evidence for the indicated interaction is presented. The shapes that outline the numbers denote whether the evidence supporting the indicated interaction are from larval studies (circle), adult studies (square) or both (diamond). Gr43a neurons, Taotie neurons and EB R4 neurons were identified in adult flies.

Figure 2.

Hunger-based control of feeding circuits. (a) In adult flies, hunger modulates GRNs (orange, green and red) and SEZ neurons (light blue) to promote food intake. Starvation increases the release of NPF, which indirectly activates the dopaminergic TH-VUM neurons that in turn potentiate sweet taste-responsive Gr5a neurons via the dopamine receptor DopEcR. Starvation also increases the release of AKH, which indirectly activates sNPF-releasing LNCs. sNPF then activates as yet unknown GABAergic neurons that inhibit the bitter taste-responsive Gr66a neurons. The same GABAergic neurons may also inhibit OA-VL neurons that can potentiate Gr66a neurons by releasing tyramine (TA) and octopamine (OA). In addition, starvation potentiates yeast taste-responsive Ir76 neurons, Fdg command neurons, cholinergic IN1 neurons, and AKHR-expressing ISNs to promote food intake. Starvation also positively regulates DH44 neurons that promote feeding (via DH44R1-expressing neurons) in response to post-ingestive amino acid and nutritious sugar signals. Dashed lines indicate the regulation is indirect or its underlying mechanism is not fully understood. a.a., amino acids. (b) In the adult central brain, protein starvation (and particularly lack of glutamine) activates dopaminergic DA-WED neurons, which activate FB-LAL neurons to promote protein intake while inhibiting PLP neurons that promote sugar consumption. (c) In fly larvae, hunger increases feeding tolerance through an NPF pathway, while also enhancing feeding rate via OA neurons. Two populations of OA neurons, OA-VUM1 and OA-VUM2, act, respectively, through OAMB- and Octβ3R-expressing neurons to contrastingly regulate feeding rate. Additionally, DILPs (release of which is inhibited by hunger) also negatively regulate feeding tolerance and feeding rate. DILPs regulate feeding tolerance via NPFR neurons, but whether they regulate feeding rate through the OA neurons remains to be determined.

Figure 3.

Hunger-based control of olfactory circuits. (a) Starvation inhibits the release of DILPs, reducing insulin signalling in both attraction and avoidance ORNs. The reduced insulin signalling leads to increased expression of sNPFR and DTKR in the attraction and avoidance ORNs, respectively. In the attraction ORNs, sNPFR receives sNPF secreted from the same ORNs, which in turn enhances their attraction to food odours. By contrast, in avoidance ORNs, DTKR receives TK from LNs in the antennal lobe and consequently repress the synaptic output of avoidance ORNs. (b) Five MBON pathways (blue) that innervate different zones of the KC axons promote odour-driven food-seeking behaviour. These MBON pathways are regulated by their corresponding dopaminergic neurons (DANs; green), and these DANs receive different combinations of hunger and satiety signals. The MP1-MVP2-M4/6 MBON pathway also mediates hunger control of learned food-seeking behaviour.