How the gastrointestinal tract communicates with the brain, via sensory nerves, is of significant interest for our understanding of human health and disease. Enterochromaffin (EC) cells in the gut mucosa release a variety of neurochemicals, including the largest quantity of 5‐hydroxytryptamine (5‐HT) in the body. How 5‐HT and other substances released from EC cells activate sensory nerve endings in the gut wall remains a major unresolved mystery. We used in vivo anterograde tracing from nodose ganglia to determine the spatial relationship between 5‐HT synthesizing and peptide‐YY (PYY)‐synthesizing EC cells and their proximity to vagal afferent nerve endings that project to the mucosa of mouse small intestine. The shortest mean distances between single 5‐HT‐ and PYY‐synthesizing EC cells and the nearest vagal afferent nerve endings in the mucosa were 33.1 ± 14.4 µm (n = 56; N = 6) and 70.3 ± 32.3 µm (n = 16; N = 6). No morphological evidence was found to suggest that 5‐HT‐ or PYY‐containing EC cells form close morphological associations with vagal afferents endings, or varicose axons of passage. The large distances between EC cells and vagal afferent endings are many hundreds of times greater than those known to underlie synaptic transmission in the nervous system (typically 10–15 nm). Taken together, the findings lead to the inescapable conclusion that communication between 5‐HT‐containing EC cells and vagal afferent nerve endings in the mucosa of the mouse small intestinal occurs in a paracrine fashion, via diffusion.New and Noteworthy None of the findings here are consistent with a view that close physical contacts occur between 5‐HT‐containing EC cells and vagal afferent nerve endings in mouse small intestine. Rather, the findings suggest that gut–brain communication between EC cells and vagal afferent endings occurs via passive diffusion. The morphological data presented do not support the view that EC cells are physically close enough to vagal afferent endings to communicate via fast synaptic transmission.

中文翻译：

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肠-脑通讯的潜在机制：肠嗜铬（EC）细胞如何激活小肠中的迷走神经传入神经末梢

胃肠道如何通过感觉神经与大脑进行交流，对于我们了解人类健康和疾病具有重要意义。肠粘膜中的肠嗜铬细胞 (EC) 释放多种神经化学物质，包括体内数量最多的 5-羟色胺 (5-HT)。 EC 细胞释放的 5-HT 和其他物质如何激活肠壁的感觉神经末梢仍然是一个未解之谜。我们使用结状神经节的体内顺行追踪来确定 5-HT 合成和肽-YY (PYY) 合成 EC 细胞之间的空间关系以及它们与投射到小鼠小肠粘膜的迷走神经传入神经末梢的接近程度。单个 5-HT 和 PYY 合成 EC 细胞与粘膜中最近的迷走神经传入神经末梢之间的最短平均距离为 33.1 ± 14.4 µm（n= 56；氮= 6) 和 70.3 ± 32.3 µm (n= 16；氮= 6）。没有发现形态学证据表明含有 5-HT 或 PYY 的 EC 细胞与迷走神经传入末梢或通道的曲张轴突形成密切的形态学关联。 EC 细胞和迷走神经传入末梢之间的距离比已知的神经系统突触传递距离（通常为 10-15 nm）大数百倍。总而言之，这些发现得出了不可避免的结论，即含有 5-HT 的 EC 细胞与小鼠小肠粘膜中的迷走神经传入神经末梢之间的通讯以旁分泌方式通过扩散发生。这里没有新的和值得注意的发现与小鼠小肠中含有 5-HT 的 EC 细胞和迷走神经传入神经末梢之间发生密切的物理接触的观点一致。相反，研究结果表明 EC 细胞和迷走神经传入末梢之间的肠脑通讯是通过被动扩散发生的。所提供的形态学数据并不支持 EC 细胞在物理上足够接近迷走神经传入末梢以通过快速突触传递进行通信的观点。