A neural circuit of food sight-promoted feeding and contextual memory in mice

Feeding is regulated not solely by intrinsic energy demands, but also by various environmental cues. Food sight and odor are two essential food-related cues that promote human eating; nonetheless, the underlying neural mechanisms remain unknown. Here, we show that during energy deficit, food sight inhibits the ventromedial hypothalamus (VMH) neuronal activity, thereby promoting feeding and food-associated contextual memory in mice. VMH neurons receive direct GABAergic input from the suprachiasmatic nucleus (SCN) that is rapidly activated by food sight. Either knockout of VMH RuvB-like 2 (RUVBL2) or inhibition of RUVBL2-expressing neurons in the VMH (VMHRUVBL2) promotes feeding and food-associated contextual memory. Interestingly, VMHRUVBL2 neurons exert these effects by sequentially projecting to the supramammillary nucleus (SuM) and the hippocampal dentate gyrus (DG). Together, this study identifies SCNGABA → VMHRUVBL2 → SuM→DG neural circuit underlying food sight-promoted feeding and food-associated contextual memory in mice. Feeding can be regulated by sensory cues. This study identifies a multi-layer circuit that mediates food sight-promoted feeding and food-related memory in mice.