Cell
Volume 175, Issue 3, 18 October 2018, Pages 665-678.e23
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Article
A Neural Circuit for Gut-Induced Reward

https://doi.org/10.1016/j.cell.2018.08.049Get rights and content
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Highlights

  • Critical role for the vagal gut-to-brain axis in motivation and reward

  • Optogenetic stimulation of the vagal gut-to-brain axis produces reward behaviors

  • Asymmetric brain pathways of vagal origin mediate motivation and dopamine activity

  • Gut-innervating vagal sensory neurons are major components of the reward circuitry

Summary

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

vagus nerve
dopamine
gut-brain axis
reward

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Present address: Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA

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