A controlled trial of a human papillomavirus type 16 vaccine. Koutsky LA, Ault KA, Wheeler CM, et al. N Engl J Med 2002; 347: 1645-1651

SUMMARY Animals are motivated to eat based on their internal need. When animals are hungry, the sensory detection of food elicits bursts of physiological changes in their bodies. This is the cephalic phase response (CPR), which prepares animals to properly digest food before nutrients enter their bodies. Despite animals uniformly exhibiting a strong CPR, to what extent and how the internal state influences CPR is largely unclear. Here, we demonstrate in Drosophila that tasting food triggers CPR, which is strongly influenced by the internal state. We found that feeding an artificial sweetener or gustatory excitation by optogenetics trigger CPR, which is a rapid and partial recovery from the starved state. While clock genes and hunger signals profoundly drive CPR, they are not required for the process of response after nutrient intake. Therefore, we propose that CPR is the critical layer of regulatory mechanisms representing internal energy homeostasis and metabolism. HIGHLIGHTS Drosophila exhibit a cephalic phase response (CPR). Sensory detection triggers CPR. Hunger signals and clock genes selectively drive CPR. Hunger signals and clock genes do not regulate the response after nutrient intake.