Appropriate feeding behavior is the foundation of maintaining homeostasis. Elevated feeding rate (binge eating) is a common trait of eating disorders, and it is associated with obesity. It is also known that flavor perception regulates feeding. However, the effects of feeding rate on sensory feedback from flavor perception remain unknown. We developed a liquid food delivery system that enables Ensure (artificial energy-dense flavored milk with high incentive salience) consumption at different feeding rates. Using miniscopes for in vivo calcium imaging in freely foraging mice, we identified distinct neuronal responses in the anterior olfactory (piriform) cortex (aPC) upon slow and binge eating; we observed clear excitatory flavor responses during slow eating but unspecific activity suppression upon binge eating. This binge-induced suppression is only observed in aPC, while neuronal responses in gustatory or somatosensory cortices remain similar in both slow and binge eating.
Mechanistically, odor inputs from olfactory bulb mitral cells remain stable upon binge eating, suggesting the suppression is not inherited from upstream elements of the olfactory pathway. Local inhibitory circuits in aPC do not play an active role in suppression, since aPC GABAergic neurons are also suppressed during binge eating. We further excluded inhibitory effects of dopaminergic and serotonergic modulation in aPC since dopamine and serotonin release are decreased upon slow and binge feeding.
We found that the strength of binge-induced suppression in the aPC predicts mice's total Ensure consumptions on different recording sessions and optogenetically suppressing aPC neurons upon binge eating in closed-loop experiments can promote feeding behaviors. Taken together, our results provide clear circuit mechanisms of binge-induced flavor modulation, which may contribute to binge-induced overeating due to reduced sensory feedback of food items.