Neuroepithelial circuit formed by innervation of sensory enteroendocrine cells.

Loading...
Thumbnail Image

Date

2015-02

Journal Title

Journal ISSN

Volume Title

Repository Usage Stats

570
views
580
downloads

Citation Stats

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.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1172/JCI78361

Publication Info

Bohórquez, DV, RA Shahid, A Erdmann, AM Kreger, Y Wang, N Calakos, F Wang, RA Liddle, et al. (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.

Scholars@Duke

Bohorquez

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 diabetes.  Yet, the most striking part of her story for me was that her perception of taste had been markedly transformed. Reshaping her gut caused her brain to convert a prior repulsion at the appearance of runny egg yolk into a strong craving to eat those same eggs.

Today, we are still a long way from understanding the full details of these intriguing conversations between our gut and our brain. But, the more we understand, the closer we are getting to treating disorders involving alterations in the perception of food in our gut.

My focus is to unveil how the brain perceives what the gut feels, how food in the intestine is sensed by our body, and how a sensory signal from a nutrient is transformed into an electrical signal that alters behavior.

Calakos

Nicole Calakos

Lincoln Financial Group Distinguished Professor of Neurobiology
Wang

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 free-moving animals) techniques to study these questions.

Liddle

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.   Cholecystokinin (CCK) is secreted from EECs of the upper small intestine and regulates the ingestion and digestion of food through effects on the stomach, gallbladder, pancreas and brain.  Peptide YY (PYY) is secreted from EECs of the small intestine and colon and regulates satiety.  We recently demonstrated that CCK and PYY cells not only secrete hormones but are directly connected to nerves through unique cellular processes called ‘neuropods’.  Our laboratory is devoted to understanding EECs signaling and its role in disease.

Pancreatitis

Pancreatitis is an inflammatory disease of the pancreas compounded by intrapancreaatic activation of digestive enzymes.  Our laboratory is studying the influence of nerves on the development of pancreatitis. Neurogenic inflammation results from the release of bioactive substances from sensory neurons in the pancreas causing vasodilatation, edema, and inflammatory cell infiltration producing tissue necrosis. Our goal is to identify the agents that activate sensory neurons, characterize the receptors on sensory nerves that mediate these actions, and determine the effects of neural stimulation on pancreatic injury with the long-term objective of developing strategies to reduce neurogenic inflammation to treat pancreatitis. 

Visit our lab page.


Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.