A Neural Circuit for Gut-Induced Reward

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 central nervous system. 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.

Vagal mechanisms as neuromodulatory targets for the treatment of metabolic disease

“…Gastrointestinal vagal afferents are channeled via the NTS to various forebrain structures, e.g., the hypothalamus and limbic areas, partly in a lateralized manner. This was exemplified by a recent study demonstrating gut-induced reward via a right-sided nodose ganglion-NTS-parabrachial nuclei pathway to midbrain dopaminergic neurons and the striatum 28 .…”

Vagus nerve stimulation increases vigor to work for rewards

“…To date, these two decisionmaking strategies have often been portrayed as (more or less) independent processes and, specifically, the role of the gut has been commonly dismissed as primarily figurative (Gigerenzer, 2007). However, there is emerging evidence from preclinical studies pointing to a vital role of gut-derived signals in the regulation of motivation via dopaminergic circuits de Araujo, Ferreira, Tellez, Ren, & Yeckel, 2012;Han et al, 2018). Although these results challenge the conclusion that the gut plays only a figurative role in human motivation, a conclusive experimental demonstration of such a modulation in humans is lacking to date.…”

Vagus nerve spiking activity associated with locomotion and cortical arousal states in a freely moving rat

“…Unveiling spike patterns of the vagus nerve is indispensable to further understand the communication between the brain and visceral organs such as the heart (Hayakawa et al., ), digestive organs (Campos et al., ; Czaja et al., ), and the lung (Han et al., ; Weijs et al., ). In previous studies, recordings of VN spikes have been performed in anesthetized rodent animals (Caravaca et al., ; Harreby et al., ; McCallum et al., ; Silverman et al., ).…”

“…The findings of the present study indicate that the VN has unique spike characteristics that are neither precisely correlated with brain activity nor accounted for simply by the dynamics of single peripheral organs. Further studies with more data sample collections from a variety of behavioral environments and physiological techniques to manipulate temporal dynamics of VN (e.g., Han et al., ) are required to reveal the functional roles of the VN in various behavioral patterns.…”

“…The majority of the vagus nerve consists of afferent sensory pathways that transmit ascending information to the nucleus of the solitary tract in the brain from the visceral organs. Especially, previous studies have revealed detailed anatomical pathways innervating from the heart (Hayakawa, Kuwahara‐Otani, Maeda, Tanaka, & Seki, ), the food intake‐related digestive organs (Campos, Wright, Czaja, & Ritter, ; Czaja, Ritter, & Burns, ), and the lung (Han et al., ; Weijs et al., ). Furthermore, the afferent vagus nerve has been targeted in studies of interoception, a neurophysiological process by which the brain monitors internal physiological states of the peripheral organs (Garfinkel & Critchley, ; Pfeifer et al., ), which leads to changes in brain functions, including cognition and emotion.…”