Binge Feeding Promotes Appetite via Modulating Olfactory Flavor Representation

Abstract Binge eating commonly leads to overeating (1; 2; 3; 4), but the exact mechanism is unclear. While it is known that experiencing flavor contributes to satiety, the interactions between flavor, feeding rate, and food intake remain unknown. Here, we demonstrate a novel feeding rate-dependent feedback loop between olfactory flavor representation in the anterior olfactory (piriform) cortex (aPC) and food intake. We developed a liquid food delivery system that allows food consumption at different feeding rates. Using miniscopes for in vivo calcium imaging in freely foraging mice, we identified specific excitatory neuronal responses to food and water during slow feeding. Switching to binge feeding transformed these specific responses into unspecific global suppression of neuronal activity. In the gustatory cortex and the olfactory bulb, we observed similarities in flavor representation during binge and slow feeding. Food consumption was predicted by the degree of suppression of neuronal activity in the aPC during binge feeding. Also, food deprivation enhanced neuronal activity suppression. We confirmed the hypothesis that aPC suppression promotes food intake with closed-loop optogenetics experiments. Together, our results show that olfactory sensory representation in the aPC reciprocally interacts with consummatory behavior to enhance food intake.