A Neural Circuit for Gut-Induced Reward

Abstract

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.

Non-invasive stimulation of vagal afferents reduces gastric frequency

“…In line with the hypothesized efferent effect, we found that taVNS alters a marker of energy homeostasis in humans. The observed taVNS-induced reduction in gastric frequency is well in line with previous findings linking VNS to altered energy homeostasis [13,14,17]. This efferent effect on gastric motility might be due to a taVNS-induced release of dopamine in the brain stem.…”

“…Such metabolic effects might be related to VNSinduced increases in the activity of brown adipose tissue, which in turn increased the basal metabolic rate [15]. Notably, dopamine has been suggested as a neuromodulator of energy homeostasis within the gut-brain axis [16,17]. Afferently, stimulation of the vagal sensory ganglion in mice was found to induce dopamine release in the substantia nigra [17].…”

“…Notably, dopamine has been suggested as a neuromodulator of energy homeostasis within the gut-brain axis [16,17]. Afferently, stimulation of the vagal sensory ganglion in mice was found to induce dopamine release in the substantia nigra [17]. Efferently, dopamine administration to the dorsal vagal complex in rats modulated the upper gastrointestinal tract by reducing gastric tone and motility via DA2 receptors in the dorsal motor nucleus of the vagus [18].…”

The vagus nerve is necessary for the rapid and widespread neuronal activation in the brain following oral administration of psychoactive bacteria

“…We chose the 165-minute time-point given that transit time to the mouse stomach and small intestine is ∼1 hour (Padmanabhan et al, 2013; Wehner et al, 2014), both of which are heavily innervated by the vagus nerve (Wang and Powley, 2000), and that c-Fos immunoreactivity in the brain peaks between 1-2 hours (Nestler et al, 2001b; Jung et al, 2014). While the data herein does not necessarily suggest that all of these distributed areas are integral to the effects of the bacteria, it aligns with previous works outlining regions that receive direct or indirect projections from the vagus nerve (Groves and Brown, 2005; Han et al, 2018), and those that are affected by vagal nerve stimulation (VNS)—an approved therapy in the treatment of refractory depression (Naritoku et al, 1995; Chae et al, 2003; Nemeroff et al, 2006; Cunningham et al, 2008; Furmaga et al, 2012; Aaronson et al, 2017). This is particularly relevant given the critical role of the vagus in mediating the behavioural effects of this particular bacterial strain (Bravo et al, 2011; Perez-Burgos et al, 2014).…”

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, 2011), digestive organs (Campos et al, 2012;Czaja et al, 2006), and the lung (Han et al, 2018;Weijs et al, 2015). In previous studies, recordings of VN spikes have been performed in anesthetized rodent animals (Caravaca et al, 2017;Harreby et al, 2011;McCallum et al, 2017;Silverman et al, 2018).…”