A neural circuit mechanism for mechanosensory feedback control of ingestion
A neural circuit mechanism for mechanosensory feedback control of ingestion
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DOI：
10.1038/s41586-020-2167-2
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发表时间：
2020-04-16
期刊：
影响因子：
64.8
通讯作者：
Kim, Sung-Yon
中科院分区：
文献类型：
--
作者：
Kim, Dong-Yoon;Heo, Gyuryang;Kim, Sung-Yon
从消化道到大脑的机械感觉反馈对于限制过量的食物和水摄入至关重要，但潜在的肠-脑通信途径和机制仍然知之甚少（1-12）。在这里，我们表明，在小鼠中，在臂旁核的神经元，表达前强啡肽基因（以下简称PBPdyn神经元）监测摄入的液体和固体，使用机械感觉信号，从上消化道。大多数单个PBPdyn神经元通过摄入以及口和胃的刺激被激活，这表明了跨消化道不同部分的综合感觉信号的表示。PBPdyn神经元在解剖学上通过颅和脊髓通路连接到消化道外周;我们发现，在这些通路中，迷走神经传递胃扩张信号到PBPdyn神经元。在接收到这些信号后，这些神经元产生厌恶和持续的食欲抑制信号，这部分地通过向室旁下丘脑发出信号来阻止进食和饮水的开始（完全再现胃扩张的症状）。相比之下，抑制相同的PBPdyn神经元群体只会在存在摄入驱动的情况下诱导过度消费，这证实了这些神经元介导负反馈信号。我们的研究结果揭示了一种神经机制，其基础是消化道扩张时对摄入的机械感觉监测和对摄入行为的负反馈控制。
Mechanosensory feedback from the digestive tract to the brain is critical for limiting excessive food and water intake, but the underlying gut-brain communication pathways and mechanisms remain poorly understood(1-12). Here we show that, in mice, neurons in the parabrachial nucleus that express the prodynorphin gene (hereafter, PBPdyn neurons) monitor the intake of both fluids and solids, using mechanosensory signals that arise from the upper digestive tract. Most individual PBPdyn neurons are activated by ingestion as well as the stimulation of the mouth and stomach, which indicates the representation of integrated sensory signals across distinct parts of the digestive tract. PBPdyn neurons are anatomically connected to the digestive periphery via cranial and spinal pathways; we show that, among these pathways, the vagus nerve conveys stomach-distension signals to PBPdyn neurons. Upon receipt of these signals, these neurons produce aversive and sustained appetite-suppressing signals, which discourages the initiation of feeding and drinking (fully recapitulating the symptoms of gastric distension) in part via signalling to the paraventricular hypothalamus. By contrast, inhibiting the same population of PBPdyn neurons induces overconsumption only if a drive for ingestion exists, which confirms that these neurons mediate negative feedback signalling. Our findings reveal a neural mechanism that underlies the mechanosensory monitoring of ingestion and negative feedback control of intake behaviours upon distension of the digestive tract.