The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
A Neural Circuit for Gut-Induced Reward
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Olds, J., & Milner, P. (1954) · Journal of Comparative and Physiological Psychology · doi:10.1037/h0058775 · Cited by 3,176
Gut feelings: the emerging biology of gut-brain communication
Mayer, E. A. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3071 · Cited by 1,726
The central nervous system and the gut microbiome
Sharon, G., Sampson, T. R., Geschwind, D. H., & Mazmanian, S. K. (2016) · Cell · doi:10.1016/j.cell.2016.10.027 · Cited by 1,513
Neurons for hunger and thirst transmit a negative-valence teaching signal
Betley, J. N., Xu, S., Cao, Z. F. H., Gong, R., Magnus, C. J., Yu, Y., & Sternson, S. M. (2015) · Nature · doi:10.1038/nature14416 · Cited by 704
Sensory neurons that detect stretch and nutrients in the digestive system
Williams, E. K., Chang, R. B., Strochlic, D. E., Umans, B. D., Lowell, B. B., & Liberles, S. D. (2016) · Cell · doi:10.1016/j.cell.2016.05.011 · Cited by 645
Genetic identification of a neural circuit that suppresses appetite
Carter, M. E., Soden, M. E., Zweifel, L. S., & Palmiter, R. D. (2013) · Nature · doi:10.1038/nature12596 · Cited by 587
Howland, R. H. (2014) · Current Behavioral Neuroscience Reports · doi:10.1007/s40473-014-0010-5 · Cited by 405
Vagal and hormonal gut-brain communication: from satiation to satisfaction
Berthoud, H. ‐. (2008) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2008.01104.x · Cited by 307
Parabrachial CGRP Neurons Control Meal Termination
Campos, C. A., Bowen, A. J., Schwartz, M. W., & Palmiter, R. D. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.04.006 · Cited by 262
The gut–brain dopamine axis: a regulatory system for caloric intake
de Araujo, I. E., Ferreira, J. G., Tellez, L. A., Ren, X., & Yeckel, C. W. (2012) · Physiology & Behavior · doi:10.1016/j.physbeh.2012.02.026 · Cited by 140
Self-citation
Cited by
The gut microbiota–brain axis in behaviour and brain disorders
Morais, L. H., Schreiber, H. L., & Mazmanian, S. K. (2021) · Nature Reviews Microbiology · doi:10.1038/s41579-020-00460-0 · Cited by 2,149
The microbiota-gut-brain axis: from motility to mood
Margolis, K. G., Cryan, J. F., & Mayer, E. A. (2021) · Gastroenterology · doi:10.1053/j.gastro.2020.10.066 · Cited by 999
Sgritta, M., Dooling, S. W., Buffington, S. A., Momin, E. N., Francis, M. B., Britton, R. A., & Costa-Mattioli, M. (2019) · Neuron · doi:10.1016/j.neuron.2018.11.018 · Cited by 865
Chen, W. G., Schloesser, D., Arensdorf, A. M., Simmons, J. M., Cui, C., Valentino, R., Gnadt, J. W., Nielsen, L., Hillaire-Clarke, C. S., Spruance, V., et al. (2021) · Trends in Neurosciences · doi:10.1016/j.tins.2020.10.007 · Cited by 707
Function and mechanisms of enteroendocrine cells and gut hormones in metabolism
Gribble, F. M., & Reimann, F. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-019-0168-8 · Cited by 670
Gut Microbe to Brain Signaling: What Happens in Vagus…
Fülling, C., Dinan, T. G., & Cryan, J. F. (2019) · Neuron · doi:10.1016/j.neuron.2019.02.008 · Cited by 590
Genetic identification of vagal sensory neurons that control feeding
Bai, L., Mesgarzadeh, S., Ramesh, K. S., Huey, E. L., Liu, Y., Gray, L. A., Aitken, T. J., Chen, Y., Beutler, L. R., Ahn, J. S., et al. (2019) · Cell · doi:10.1016/j.cell.2019.10.031 · Cited by 494
The role of inflammation and the gut microbiome in depression and anxiety
Peirce, J. M., & Alviña, K. (2019) · Journal of Neuroscience Research · doi:10.1002/jnr.24476 · Cited by 466
Microbiota and the social brain
Sherwin, E., Bordenstein, S. R., Quinn, J. L., Dinan, T. G., & Cryan, J. F. (2019) · Science · doi:10.1126/science.aar2016 · Cited by 462
Microbiota-Gut-Brain Axis: New Therapeutic Opportunities
Long-Smith, C., O'Riordan, K. J., Clarke, G., Stanton, C., Dinan, T. G., & Cryan, J. F. (2020) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010919-023628 · Cited by 419
The Possible Role of the Microbiota-Gut-Brain-Axis in Autism Spectrum Disorder
Srikantha, P., & Mohajeri, M. H. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20092115 · Cited by 400
Is oxytocin “nature’s medicine”
Carter, C. S., Kenkel, W. M., MacLean, E. L., Wilson, S. R., Perkeybile, A. M., Yee, J. R., Ferris, C. F., Nazarloo, H. P., Porges, S. W., Davis, J. M., et al. (2020) · Pharmacological Reviews · doi:10.1124/pr.120.019398 · Cited by 394
Meta‐Analysis of Gut Dysbiosis in Parkinson's Disease
Nishiwaki, H., Ito, M., Ishida, T., Hamaguchi, T., Maeda, T., Kashihara, K., Tsuboi, Y., Ueyama, J., Shimamura, T., Mori, H., et al. (2020) · Movement Disorders · doi:10.1002/mds.28119 · Cited by 370
“Liking” and “wanting” in eating and food reward: Brain mechanisms and clinical implications
Morales, I., & Berridge, K. C. (2020) · Physiology & Behavior · doi:10.1016/j.physbeh.2020.113152 · Cited by 346
Role of the gut-brain axis in energy and glucose metabolism
Wachsmuth, H. R., Weninger, S. N., & Duca, F. A. (2022) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00677-w · Cited by 269
Central and peripheral GLP-1 systems independently suppress eating
Brierley, D. I., Holt, M. K., Singh, A., de Araujo, A., McDougle, M., Vergara, M., Afaghani, M. H., Lee, S. J., Scott, K., Maske, C., et al. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00344-4 · Cited by 265
Han, Y., Wang, B., Gao, H., He, C., Hua, R., Liang, C., Zhang, S., Wang, Y., Xin, S., & Xu, J. (2022) · Journal of Inflammation Research · doi:10.2147/jir.s384949 · Cited by 265
Conversano, C., Ciacchini, R., Orrù, G., Di Giuseppe, M., Gemignani, A., & Poli, A. (2020) · Frontiers in Psychology · doi:10.3389/fpsyg.2020.01683 · Cited by 243
Neuropod Cells: The Emerging Biology of Gut-Brain Sensory Transduction
Kaelberer, M. M., Rupprecht, L. E., Liu, W. W., Weng, P., & Bohórquez, D. V. (2020) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-091619-022657 · Cited by 236
Self-citationInteroceptive rhythms in the brain
Engelen, T., Solcà, M., & Tallon-Baudry, C. (2023) · Nature Neuroscience · doi:10.1038/s41593-023-01425-1 · Cited by 207
Integrative neurocircuits that control metabolism and food intake
Brüning, J. C., & Fenselau, H. (2023) · Science · doi:10.1126/science.abl7398 · Cited by 214
Liu, C.-H., Yang, M.-H., Zhang, G.-Z., Wang, X.-X., Li, B., Li, M., Woelfer, M., Walter, M., & Wang, L. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01732-5 · Cited by 210
Microbial-derived metabolites as a risk factor of age-related cognitive decline and dementia
Connell, E., Le Gall, G., Pontifex, M. G., Sami, S., Cryan, J. F., Clarke, G., Müller, M., & Vauzour, D. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00548-6 · Cited by 208
Processed foods and food reward
Small, D. M., & DiFeliceantonio, A. G. (2019) · Science · doi:10.1126/science.aav0556 · Cited by 195
An inter-organ neural circuit for appetite suppression
Zhang, T., Perkins, M. H., Chang, H., Han, W., & de Araujo, I. E. (2022) · Cell · doi:10.1016/j.cell.2022.05.007 · Cited by 192
Self-citationThe physiological control of eating: signals, neurons, and networks
Watts, A. G., Kanoski, S. E., Sanchez-Watts, G., & Langhans, W. (2022) · Physiological Reviews · doi:10.1152/physrev.00028.2020 · Cited by 168
Checa-Ros, A., Jeréz-Calero, A., Molina-Carballo, A., Campoy, C., & Muñoz-Hoyos, A. (2021) · Nutrients · doi:10.3390/nu13010249 · Cited by 164
Microbiota-modulated CART + enteric neurons autonomously regulate blood glucose
Muller, P. A., Matheis, F., Schneeberger, M., Kerner, Z., Jové, V., & Mucida, D. (2020) · Science · doi:10.1126/science.abd6176 · Cited by 154
Neural Control and Modulation of Thirst, Sodium Appetite, and Hunger
Augustine, V., Lee, S., & Oka, Y. (2020) · Cell · doi:10.1016/j.cell.2019.11.040 · Cited by 135
Microbiota–neuroepithelial signalling across the gut–brain axis
Ohara, T. E., & Hsiao, E. Y. (2025) · Nature Reviews Microbiology · doi:10.1038/s41579-024-01136-9 · Cited by 147
Cheng, W., Gonzalez, I., Pan, W., Tsang, A. H., Adams, J., Ndoka, E., Gordian, D., Khoury, B., Roelofs, K., Evers, S. S., et al. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2019.12.012 · Cited by 123
Bacterial Peptidoglycans from Microbiota in Neurodevelopment and Behavior
Gonzalez-Santana, A., & Diaz Heijtz, R. (2020) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2020.05.003 · Cited by 118
A Role for GLP-1 in Treating Hyperphagia and Obesity
Grill, H. J. (2020) · Endocrinology · doi:10.1210/endocr/bqaa093 · Cited by 101
Dargenio, V. N., Dargenio, C., Castellaneta, S., De Giacomo, A., Laguardia, M., Schettini, F., Francavilla, R., & Cristofori, F. (2023) · Nutrients · doi:10.3390/nu15071620 · Cited by 98
Krieger, J.-P. (2020) · Peptides · doi:10.1016/j.peptides.2020.170342 · Cited by 91
Satiety: a gut–brain–relationship
Barakat, G. M., Ramadan, W., Assi, G., & Khoury, N. B. E. (2024) · The Journal of Physiological Sciences · doi:10.1186/s12576-024-00904-9 · Cited by 82
Buijs, R. M., Guzmán Ruiz, M. A., Méndez Hernández, R., & Rodríguez Cortés, B. (2019) · Autonomic Neuroscience · doi:10.1016/j.autneu.2019.02.001 · Cited by 63
Vagus nerve stimulation modulates hippocampal inflammation caused by continuous stress in rats
Namgung, U., Kim, K.-J., Jo, B.-G., & Park, J.-M. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02396-z · Cited by 59
The microbiome and gut endocannabinoid system in the regulation of stress responses and metabolism
Srivastava, R. K., Lutz, B., & Ruiz de Azua, I. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.867267 · Cited by 56
Brain control of energy homeostasis: implications for anti-obesity pharmacotherapy
Johansen, V. B. I., Petersen, J., Lund, J., Mathiesen, C. V., Fenselau, H., & Clemmensen, C. (2025) · Cell · doi:10.1016/j.cell.2025.06.010 · Cited by 53
McDougle, M., Quinn, D., Diepenbroek, C., Singh, A., de la Serre, C., & de Lartigue, G. (2021) · Acta Physiologica · doi:10.1111/apha.13530 · Cited by 42
Self-citationPhysiological integration of taste and metabolism
Egan, J. M. (2024) · New England Journal of Medicine · doi:10.1056/nejmra2304578 · Cited by 40
How gut hormones shape reward: A systematic review of the role of ghrelin and GLP-1 in human fMRI
Schulz, C., Vezzani, C., & Kroemer, N. B. (2023) · Physiology & Behavior · doi:10.1016/j.physbeh.2023.114111 · Cited by 33
Narrative review on potential role of gut microbiota in certain substance addiction
Qin, C., Hu, J., Wan, Y., Cai, M., Wang, Z., Peng, Z., Liao, Y., Li, D., Yao, P., Liu, L., et al. (2021) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2020.110093 · Cited by 32
The vagus nerve mediates the stomach-brain coherence in rats
Cao, J., Wang, X., Chen, J., Zhang, N., & Liu, Z. (2022) · NeuroImage · doi:10.1016/j.neuroimage.2022.119628 · Cited by 25
Self-citationLakosa, A., Rahimian, A., Tomasi, F., Marti, F., Reynolds, L. M., Tochon, L., David, V., Danckaert, A., Canonne, C., Tahraoui, S., et al. (2023) · Neuropsychopharmacology · doi:10.1038/s41386-023-01563-x · Cited by 10
Cao, J., Wang, X., Powley, T. L., & Liu, Z. (2021) · Journal of Neural Engineering · doi:10.1088/1741-2552/ac2ec6 · Cited by 10
Self-citationImmediate glucose signaling transmitted via the vagus nerve in gut–brain neural communication
Yamada, S., Natsubori, A., Harada, K., Tsuboi, T., & Monai, H. (2025) · iScience · doi:10.1016/j.isci.2025.112439 · Cited by 7
Metadata
- Authors
- Han, W., Tellez, L. A., Perkins, M. H., Perez, I. O., Qu, T., Ferreira, J., Ferreira, T. L., Quinn, D., Liu, Z.-W., Gao, X.-B., Kaelberer, M. M., Bohórquez, D. V., Shammah-Lagnado, S. J., de Lartigue, G., & de Araujo, I. E.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-10
- Volume
- 175
- Issue
- 3
- Pages
- 665-678.e23
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2890470934
- Cited by
- 729
- References
- 10
- FWCI
- 25.78
- Type
- journal article
- Language
- en
- Open access
- bronze
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
