Neuroepithelial circuit formed by innervation of sensory enteroendocrine cells.
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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.
Published Version (Please cite this version)10.1172/JCI78361
Publication InfoBohórquez, Diego V; Calakos, Nicole; Erdmann, A; Kreger, AM; Liddle, Rodger Alan; Shahid, Rafiq; ... Wang, Y (2015). Neuroepithelial circuit formed by innervation of sensory enteroendocrine cells. J Clin Invest, 125(2). pp. 782-786. 10.1172/JCI78361. Retrieved from http://hdl.handle.net/10161/9363.
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Assistant 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
Professor in Neurology
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
Morris N. Broad Distinguished Professor
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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