1. Genetic Identification of Vagal Sensory Neurons That Control Feeding
- Author
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Bai, Ling, Mesgarzadeh, Sheyda, Ramesh, Karthik S, Huey, Erica L, Liu, Yin, Gray, Lindsay A, Aitken, Tara J, Chen, Yiming, Beutler, Lisa R, Ahn, Jamie S, Madisen, Linda, Zeng, Hongkui, Krasnow, Mark A, and Knight, Zachary A
- Subjects
Biological Sciences ,Biomedical and Clinical Sciences ,Neurosciences ,Nutrition ,Obesity ,Digestive Diseases ,Underpinning research ,1.1 Normal biological development and functioning ,Oral and gastrointestinal ,Agouti-Related Protein ,Animals ,Brain ,Feeding Behavior ,Gastrointestinal Tract ,Genetic Markers ,Genetic Phenomena ,Mechanoreceptors ,Mice ,Sensory Receptor Cells ,Vagus Nerve ,Viscera ,AgRP Neurons ,RNA sequencing ,chemogenetics ,fiber photometry ,hypothalamus ,optogenetics ,satiation ,stretch ,vagal afferents ,vagus nerve ,Medical and Health Sciences ,Developmental Biology ,Biological sciences ,Biomedical and clinical sciences - Abstract
Energy homeostasis requires precise measurement of the quantity and quality of ingested food. The vagus nerve innervates the gut and can detect diverse interoceptive cues, but the identity of the key sensory neurons and corresponding signals that regulate food intake remains unknown. Here, we use an approach for target-specific, single-cell RNA sequencing to generate a map of the vagal cell types that innervate the gastrointestinal tract. We show that unique molecular markers identify vagal neurons with distinct innervation patterns, sensory endings, and function. Surprisingly, we find that food intake is most sensitive to stimulation of mechanoreceptors in the intestine, whereas nutrient-activated mucosal afferents have no effect. Peripheral manipulations combined with central recordings reveal that intestinal mechanoreceptors, but not other cell types, potently and durably inhibit hunger-promoting AgRP neurons in the hypothalamus. These findings identify a key role for intestinal mechanoreceptors in the regulation of feeding.
- Published
- 2019