Neuroepithelial circuit formed by innervation of sensory enteroendocrine cells.
Abstract
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.
Type
Journal articleSubject
AnimalsCell Communication
Cells, Cultured
Coculture Techniques
Colon
Enteroendocrine Cells
Intestine, Small
Mice
Neuroepithelial Cells
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https://hdl.handle.net/10161/9363Published Version (Please cite this version)
10.1172/JCI78361Publication Info
Bohórquez, DV; Shahid, RA; Erdmann, A; Kreger, AM; Wang, Y; Calakos, N; ... Liddle,
RA (2015). Neuroepithelial circuit formed by innervation of sensory enteroendocrine cells. J Clin Invest, 125(2). pp. 782-786. 10.1172/JCI78361. Retrieved from https://hdl.handle.net/10161/9363.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Diego V. Bohorquez
Associate Professor in Medicine
I am a gut-brain neuroscientist. Though my initial studies focused on GI physiology
and nutrition, my expertise evolved to include neuroscience following the many personal
stories, which have carefully sharpened my career vision along the way. While pursuing
a Doctoral degree in Nutrition, a friend shared her struggles with obesity and gastric
bypass surgery. Surgery was a last resort but helped to reduced her body weight dramatically
and resolved her diabe
Nicole Calakos
Lincoln Financial Group Distinguished Professor of Neurobiology
Rodger Alan Liddle
Professor of Medicine
Our laboratory has two major research interests:Enteroendocrine Cell Biology
Enteroendocrine cells (EECs) are sensory cells of the gut that send signals throughout
the body. They have the ability to sense food and nutrients in the lumen of the intestine
and secrete hormones into the blood. Our laboratory has had a longstanding interest
in two types of EECs that regulate satiety and signal the brain to stop eating. Chole
Fan Wang
Adjunct Professor in the Department of Neurobiology
My lab studies neural circuit basis of sensory perception. Specifically we are interested
in determining neural circuits underlying (1) active touch sensation including tactile
processing stream and motor control of touch sensors on the face; (2) pain sensation
including both sensory-discriminative and affective aspects of pain; and (3) general
anesthesia including the active pain-suppression process. We use a combination of
genetic, viral, electrophysiology, and in vivo imaging (in f
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