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Neuroepithelial circuit formed by innervation of sensory enteroendocrine cells
Open accessAbstract
Satiety and other core physiological functions are modulated by sensory signals arising from the surface of the gut. Luminal nutrients and bacteria stimulate epithelial biosensors called enteroendocrine cells. Despite being electrically excitable, enteroendocrine cells are generally thought to communicate indirectly with nerves through hormone secretion and not through direct cell-nerve contact. However, we recently uncovered in intestinal enteroendocrine cells a cytoplasmic process that we named neuropod. Here, we determined that neuropods provide a direct connection between enteroendocrine cells and neurons innervating the small intestine and colon. Using cell-specific transgenic mice to study neural circuits, we found that enteroendocrine cells have the necessary elements for neurotransmission, including expression of genes that encode pre-, post-, and transsynaptic proteins. This neuroepithelial circuit was reconstituted in vitro by coculturing single enteroendocrine cells with sensory neurons. We used a monosynaptic rabies virus to define the circuit's functional connectivity in vivo and determined that delivery of this neurotropic virus into the colon lumen resulted in the infection of mucosal nerves through enteroendocrine cells. This neuroepithelial circuit can serve as both a sensory conduit for food and gut microbes to interact with the nervous system and a portal for viruses to enter the enteric and central nervous systems.
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“A basolateral cytoplasmic process of the L cells -the neuropod -was shown to establish a functional synaptic contact with the enteric glia and vagal afferents.”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Bohorquez et al., 2015
Experimental — accuracy not yet measuredIn the citing paper
“Enteroendocrine and enterochromaffin cells (ECCs) form close synaptic connections with certain vagal afferent fibers through cell extensions called neuropods [25, 26].”
From Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders (2022) · cites this paper as [26]
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Influential
Metadata
- Authors
- Bohórquez, D. V., Shahid, R. A., Erdmann, A., Kreger, A. M., Wang, Y., Calakos, N., Wang, F., & Liddle, R. A.
- Affiliations
- Duke Medical Center (US)
- Durham VA Medical Center (US)
- Venue
- Journal of Clinical Investigation
- Published
- 2015-01-02
- Volume
- 125
- Issue
- 2
- Pages
- 782-786
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC4319442
- OpenAlex
- W2119429325
- Cited by
- 484
- References
- 28
- Citations by year
- 2026: 42 · 2025: 51 · 2024: 45 · 2023: 45 · 2022: 47 · 2021: 60 · 2020: 47 · 2019: 38 · 2018: 41 · 2017: 22 · 2016: 29 · 2015: 17
- FWCI
- 38.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DukeSpace (Duke University) (submittedVersion)
- DukeSpace (Duke University) (submittedVersion, cc-by-nc-nd)
- Funders
- U.S. Department of Veterans Affairs (I01 BX002230)
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (F32DK094704, R01DK098796, R01DK091946, K01DK103832)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- enteroendocrine cells, sensory neurons, enteric nervous system, neurotransmission, gut-brain signaling, satiety, rabies virus, small intestine
- MeSH terms
- Animals, Cell Communication, Cells, Cultured, Colon, Intestine, Small, Coculture Techniques, Enteroendocrine Cells, Neuroepithelial Cells, Mice
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