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Cell. 2018 Oct 18;175(3):665-678.e23. doi: 10.1016/j.cell.2018.08.049. Epub 2018 Sep 20.

A Neural Circuit for Gut-Induced Reward.

Author information

1
The John B. Pierce Laboratory, New Haven, CT, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA; Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
2
The John B. Pierce Laboratory, New Haven, CT, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
3
Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
4
The John B. Pierce Laboratory, New Haven, CT, USA; Section of Neurobiology of Oral Sensations, FES-Iztacala, National Autonomous University of Mexico, Mexico City, Mexico.
5
The John B. Pierce Laboratory, New Haven, CT, USA.
6
The John B. Pierce Laboratory, New Haven, CT, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA; Department of Anatomy, Biomedical Sciences Institute, University of São Paulo, São Paulo, São Paulo, Brazil.
7
The John B. Pierce Laboratory, New Haven, CT, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA; Mathematics, Computing and Cognition Center, Federal University of ABC, São Bernardo do Campo, São Paulo, Brazil.
8
Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA.
9
Department of Medicine, Duke University, Durham, NC, USA.
10
Department of Medicine, Duke University, Durham, NC, USA; Department of Neurobiology, Duke University, Durham, NC, USA.
11
Department of Physiology and Biophysics, Biomedical Sciences Institute, University of São Paulo, São Paulo, São Paulo, Brazil.
12
The John B. Pierce Laboratory, New Haven, CT, USA; Department of Physiology, Yale University School of Medicine, New Haven, CT, USA.
13
The John B. Pierce Laboratory, New Haven, CT, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA; Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Physiology, Yale University School of Medicine, New Haven, CT, USA. Electronic address: ivan.dearaujo@mssm.edu.

Abstract

The gut is now recognized as a major regulator of motivational and emotional states. However, the relevant gut-brain neuronal circuitry remains unknown. We show that optical activation of gut-innervating vagal sensory neurons recapitulates the hallmark effects of stimulating brain reward neurons. Specifically, right, but not left, vagal sensory ganglion activation sustained self-stimulation behavior, conditioned both flavor and place preferences, and induced dopamine release from Substantia nigra. Cell-specific transneuronal tracing revealed asymmetric ascending pathways of vagal origin throughout the CNS. In particular, transneuronal labeling identified the glutamatergic neurons of the dorsolateral parabrachial region as the obligatory relay linking the right vagal sensory ganglion to dopamine cells in Substantia nigra. Consistently, optical activation of parabrachio-nigral projections replicated the rewarding effects of right vagus excitation. Our findings establish the vagal gut-to-brain axis as an integral component of the neuronal reward pathway. They also suggest novel vagal stimulation approaches to affective disorders.

KEYWORDS:

dopamine; gut-brain axis; reward; vagus nerve

PMID:
30245012
PMCID:
PMC6195474
[Available on 2019-10-18]
DOI:
10.1016/j.cell.2018.08.049

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