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.
In our paper, we map a gut-to-brain neural circuit linking sensory neurons in the upper gut to striatal dopamine release. It has come to our attention that during the preparation of Figure 4, we inadvertently duplicated the left image of panel 4M as 4N (depicting the CGRP-positive neurons and rabies-infected fields within the PBNdl and PBNel of DAT-ires-Cre and VGat-ires-Cre mice, respectively). Upon discovering this error, we returned to the original images. During the revision process to improve the data representation, the fluorescent signals were re-colored, and we realized that we mistakenly added the same panel twice when assembling the figures for resubmission. We have generated accurate versions of Figure 4M and 4N from the original data files, which are shown below. This error, which has been corrected online and in the print version, in no way affects the results of the paper or the interpretation of the data, and we have carefully evaluated all the images in the manuscript to ensure no other errors occurred. We apologize for any confusion or inconvenience this error may have caused.
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