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 enteroendocrinecells. Despite being electrically excitable, enteroendocrinecells are generally thought to communicate indirectly with nerves through hormone secretion and not through direct cell-nerve contact.
However, we recently uncovered in intestinalenteroendocrinecells a cytoplasmic process that we named neuropod. Here, we determined that neuropods provide a direct connection between enteroendocrinecells and neurons innervating the small intestine and colon.
Using cell-specific transgenic mice to study neural circuits, we found thatenteroendocrinecells have the necessary elements for neurotransmission, including expression of genes that encode pre-, post-, and transsynaptic proteins.
This neuroepithelialcircuit was reconstituted in vitro by coculturing single enteroendocrinecells 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 enteroendocrinecells.
This neuroepithelialcircuit 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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