A Neural Circuit for Gut-Induced Reward

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


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Afferent Pathways / metabolism
  • Afferent Pathways / physiology
  • Animals
  • Dopamine / metabolism
  • Dopaminergic Neurons / physiology
  • Glutamic Acid / metabolism
  • Intestines / innervation
  • Intestines / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Optogenetics
  • Reward*
  • Substantia Nigra / physiology*
  • Vagus Nerve / physiology*


  • Glutamic Acid
  • Dopamine