Highly selective brain-to-gut communication via genetically defined vagus neurons

Author: Jenkang Tao1, John N Campbell2, Linus T Tsai3, Chen Wu3, Stephen D Liberles4, Bradford B Lowell5
Affiliation:
1 Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA.
2 Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Department of Biology, University of Virginia, Charlottesville, VA 22904, USA. Electronic address: jnc4e@virginia.edu.
3 Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
4 Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
5 Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA. Electronic address: blowell@bidmc.harvard.edu.
Conference/Journal: Neuron
Date published: 2021 May 25
Other: Special Notes: doi: 10.1016/j.neuron.2021.05.004. , Word Count: 175


The vagus nerve innervates many organs, and most, if not all, of its motor fibers are cholinergic. However, no one knows its organizing principles-whether or not there are dedicated neurons with restricted targets that act as "labeled lines" to perform certain functions, including two opposing ones (gastric contraction versus relaxation). By performing unbiased transcriptional profiling of DMV cholinergic neurons, we discovered seven molecularly distinct subtypes of motor neurons. Then, by using subtype-specific Cre driver mice, we show that two of these subtypes exclusively innervate the glandular domain of the stomach where, remarkably, they contact different enteric neurons releasing functionally opposing neurotransmitters (acetylcholine versus nitric oxide). Thus, the vagus motor nerve communicates via genetically defined labeled lines to control functionally unique enteric neurons within discrete subregions of the gastrointestinal tract. This discovery reveals that the parasympathetic nervous system utilizes a striking division of labor to control autonomic function.

Keywords: RNA sequencing; Vagus nerve; autonomic nervous system; digestion; dorsal motor nucleus of the vagus; enteric neurons; parasympathetic nervous system; peripheral nervous system; stomach.

PMID: 34077742 DOI: 10.1016/j.neuron.2021.05.004

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