FUNCTIONAL ORGANIZATION OF THE VAGAL-ENTERIC INTERFACE

肠道神经系统在胃肠道的许多功能中起着关键作用，如营养物质的运输、消化和吸收，以及对膳食毒素和抗原的防御等，并且越来越多地与一些胃肠道疾病有关。虽然肠道神经系统可以自主地进行局部控制，但其综合功能受到中枢神经系统的强烈调节，特别是通过迷走神经。因此，迷走神经调节胃肠功能是一种机制，通过这种机制，一方面，外部和内部事件可以导致适应性和生理上的有益影响，另一方面，情绪状态，如压力，可能会导致适应不良效果和疾病。这项提议旨在定义迷走神经流出和肠道神经元之间的接口，肠神经元是肠道神经系统的功能单位。拟议的研究应该回答的一些问题是：迷走神经流出是以特定功能的方式组织的吗？特异性是由节后肠神经节后迷走神经节前神经元的神经化学表型编码的吗？在小肠中，所谓的“指挥神经元”有什么特征？肽和其他共递质在迷走神经流出系统中的功能作用是什么？将使用现代解剖学、分子神经化学和细胞和组织水平的功能方法，以及一种创新的新方法来研究整合的肠道运动。这些结果将确定潜在的神经底物，并表征迷走神经调节关键肠段的功能效应，如胃、下食道和幽门括约肌、小肠和结肠。这一发现将导致对中枢神经控制正常胃肠功能的新见解。它们还可能提供重要的新线索，关于身体和情绪应激以及酒精对胃和十二指肠病变发展的影响，以及关于人类胃食道反流的问题。最后，拟议的研究将有助于了解许多胃肠动力障碍、急性细菌感染引起的胃淤滞以及炎症性肠病的长期后遗症中的神经成分。

The enteric nervous system is a key player in many functions of the gastrointestinal tract, such as transport, digestion and absorption of nutrients and defense against dietary toxins and antigens, and it has been more and more implicated in a number of gastrointestinal diseases. Although the enteric nervous system can act autonomously for local control, its integrative functions are strongly modulated by the central nervous system, in particular via the vagus nerve. Vagal modulation of gastrointestinal function is thus one of the mechanisms by which, on one hand, external and internal events can lead to adaptive and physiologically beneficial effects and, on the other hand, emotional states such as stress can lead to maladaptive effects and disease. This proposal is designed to define the interface between vagal outflow and enteric neurons, the functional units of the enteric nervous system. Some of the questions that should be answered by the proposed studies are: Is vagal outflow organized in a function-specific manner? Is specificity encoded by the neurochemical phenotype of vagal preganglionic neurons of postganglionic, enteric neurons? What are the characteristics of so-called "command neurons" in the small intestine? What is the functional role of peptides and other co-transmitters in the vagal outflow system? Modern anatomical, molecular- neurochemical, and functional approaches at the cellular and tissue level, as well as an innovative new method to study integrated gut motility will be used. The results will identify the underlying neural substrate and characterize the functional effects of vagal modulation of key gut segments such as the stomach, lower esophageal and pyloric sphincters, small intestine and colon. The findings will lead to new insights about central neural control of normal gastrointestinal function. They may also provide important new clues concerning the effects of physical and emotional stress as well as alcohol on the development of gastric and duodenal lesions and concerning the problem of human gastroesophageal reflux. Finally, the proposed studies will help understand the neural component in the many gastrointestinal motility disorders, gastric stasis induced by acute bacterial infection, and in the longer-term sequelae of inflammatory bowel disease.