PT - JOURNAL ARTICLE AU - Ling Bai AU - Nilla Sivakumar AU - Sheyda Mesgarzadeh AU - Tom Ding AU - Truong Ly AU - Timothy V. Corpuz AU - James C.R. Grove AU - Brooke C. Jarvie AU - Zachary A. Knight TI - Enteroendocrine cell types that drive food reward and aversion AID - 10.1101/2021.11.05.467492 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.11.05.467492 4099 - http://biorxiv.org/content/early/2021/11/07/2021.11.05.467492.short 4100 - http://biorxiv.org/content/early/2021/11/07/2021.11.05.467492.full AB - Animals must learn through experience which foods are nutritious and should be consumed, and which are toxic and should be avoided. Enteroendocrine cells (EECs) are the principal chemosensors in the GI tract, but investigation of their role in behavior has been limited by the difficulty of selectively targeting these cells in vivo. Here we describe an intersectional genetic approach for manipulating EEC subtypes in behaving mice. We show that multiple EEC subtypes inhibit food intake but have different effects on learning. Conditioned flavor preference is driven by release of cholecystokinin whereas conditioned taste aversion is mediated by serotonin and substance P. These positive and negative valence signals are transmitted by vagal and spinal afferents, respectively. These findings establish a cellular basis for how chemosensing in the gut drives learning about food.Competing Interest StatementThe authors have declared no competing interest.