Energy homeostasis requires precise measurement of the quantity and quality of ingested food. The vagus nerve innervates the gut and can detect diverse interoceptive cues, but the identity of the key sensory neurons and corresponding signals that regulate food intake remains unknown. Here, we use an approach for target-specific, single-cell RNA sequencing to generate a map of the vagal cell types that innervate the gastrointestinal tract. We show that unique molecular markers identify vagal neurons with distinct innervation patterns, sensory endings, and function. Surprisingly, we find that food intake is most sensitive to stimulation of mechanoreceptors in the intestine, whereas nutrient-activated mucosal afferents have no effect. Peripheral manipulations combined with central recordings reveal that intestinal mechanoreceptors, but not other cell types, potently and durably inhibit hunger-promoting AgRP neurons in the hypothalamus. These findings identify a key role for intestinal mechanoreceptors in the regulation of feeding.

中文翻译：

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控制进食的迷走神经感觉神经元的遗传鉴定。

能量稳态需要精确测量摄入食物的数量和质量。迷走神经支配肠道并可以检测多种内感受线索，但关键感觉神经元的身份和调节食物摄入的相应信号仍然未知。在这里，我们使用一种针对特定目标的单细胞 RNA 测序方法来生成支配胃肠道的迷走神经细胞类型图。我们表明，独特的分子标记可识别具有不同神经支配模式、感觉末梢和功能的迷走神经元。令人惊讶的是，我们发现食物摄入对肠道机械感受器的刺激最敏感，而营养激活的粘膜传入没有影响。外周操作与中央记录相结合表明肠道机械感受器，但不是其他细胞类型，有效且持久地抑制下丘脑中促进饥饿的 AgRP 神经元。这些发现确定了肠道机械感受器在进食调节中的关键作用。