The Neuroepithelial Landscape of Enterochromaffin Cells Varies Across Gastrointestinal Location

BACKGROUND AND AIMS: Enteroendocrine cells (EECs) lining the gastrointestinal (GI) wall sense chemical and mechanical changes in the gut, secreting an array of hormones and neurotransmitters in response. Enterochromaffin (EC) cells synthesize and secrete serotonin and represent approximately half of all EECs. EEC signals are transmitted to the brain via activation of afferent nerve fibers terminating in the GI tract. EECs grow neurite-like processes termed by some as "neuropods." These are proposed to contact intrinsic and extrinsic afferent nerves innervating the gut wall as the site of formation of a neuroepithelial circuit that signals from gut to both enteric and central nervous systems. METHODS: This study focused on investigating, along the length of the mouse GI tract, the spatial relationship between EC cells and sensory nerve fibers, all of which contain the neuropeptide CGRP. This was analyzed using confocal laser scanning microscopy and Imaris 3-dimensional image analysis. Our aim was to determine the potential relevance of cell processes as the sites of neurotransmission on EC cells. RESULTS: We found the number of contacts between EC cells and CGRP fibers increases along the GI tract, with maximal contacts occurring in the distal colon. These contacts localized primarily on the cell body, and not on processes. Further, a high degree of variability in EC cell architecture, including the frequency and size of processes was seen. CONCLUSIONS: These findings do not support the notion that EEC processes are a primary cell location at which a neuroepithelial circuit is formed but do indicate that the likelihood of such contact points occurring increases in more distal areas of the GI tract.