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Cell. 2019 Nov 14;179(5):1129-1143.e23. doi: 10.1016/j.cell.2019.10.031.

Genetic Identification of Vagal Sensory Neurons That Control Feeding.

Author information

1
Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA 94158, USA.
2
Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
3
Department of Biochemistry, Stanford University School of Medicine, Howard Hughes Medical Institute, Stanford, CA 94305-5307, USA.
4
Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA 94158, USA; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
5
Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
6
Allen Institute for Brain Science, Seattle, WA, USA.
7
Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA 94158, USA; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: zachary.knight@ucsf.edu.

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.

KEYWORDS:

AgRP Neurons; RNA sequencing; chemogenetics; fiber photometry; hypothalamus; optogenetics; satiation; stretch; vagal afferents; vagus nerve

PMID:
31730854
DOI:
10.1016/j.cell.2019.10.031

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