ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2019) 16 15.11 | DOI: 10.1530/ey.16.15.11


To read the full abstract: Cell. 2018 Oct 18;175(3):665–678.e23.

This article reports a critical role for the vagal gut-to-brain axis in motivation and reward amongst the sensory cells of the right vagal nerve. Optogenetic stimulation of the mouse vagal gut-to-brain axis produced reward behaviors. Stimulation of gut-innervating vagal sensory neurons recapped the hallmark effects of stimulating the right, but not left, vagal sensory ganglion, induced dopamine release from the Substantia nigra, sustained self-stimulation behavior, and conditioned both flavour and place preferences.

It challenges the long-held assumption that vagal sensory neurons only inhibit reward circuits and thereby suppress motivational behavior. Transneuronal optic labeling identified the glutamatergic neurons of the dorsolateral parabrachial pons (relays information from the taste area of the solitary nucleus to the ventral posteromedial nucleus of the thalamus) as the obligatory communication linking the right vagal sensory ganglion to dopamine cells in Substantia nigra.

These findings more specifically imply that food reinforcement and satiation should not be considered mutually exclusive physiological processes. Consistently, activating the hypothalamic AgRP-positive “drive” neurons counteract parabrachium-mediated satiety, while conveying negative attractiveness (averseness). Thus, nodose neurons (the inferior ganglion of vagus nerve) mediate reward signals. The right nodose neurons may be particularly sensitive to nutritive signals, whereas the left nodose neurons induced satiation, independently of reward, may preferentially display responses to mechanical distention.

Intuitively we suspected, but it now has scientific evidence: the gut is a major regulator of motivational and emotional states. Moreover, vagal stimulation may become an approach to affective disorders. Accordingly, one possible approach around cardiac complications of satiety drugs may be implanting the stimulator on vagal nerve segments located at the vicinity of the upper gut.

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