Enteroendocrine cell types that drive food reward and aversion
Ling Bai,
Nilla Sivakumar,
Shenliang Yu,
Sheyda Mesgarzadeh,
Tom Ding,
Truong Ly,
Timothy V Corpuz,
James CR Grove,
Brooke C Jarvie,
Zachary A Knight
Affiliations
Ling Bai
Department of Physiology, University of California, San Francisco, San Francisco, United States; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, United States
Nilla Sivakumar
Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States
Shenliang Yu
Department of Physiology, University of California, San Francisco, San Francisco, United States; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, United States
Department of Physiology, University of California, San Francisco, San Francisco, United States; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, United States
Tom Ding
Department of Physiology, University of California, San Francisco, San Francisco, United States; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, United States
Truong Ly
Department of Physiology, University of California, San Francisco, San Francisco, United States; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, United States; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, United States
Timothy V Corpuz
Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States
James CR Grove
Department of Physiology, University of California, San Francisco, San Francisco, United States; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, United States; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, United States
Brooke C Jarvie
Department of Physiology, University of California, San Francisco, San Francisco, United States; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, United States
Department of Physiology, University of California, San Francisco, San Francisco, United States; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, United States; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, United States
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.
