CNS CONTROL OF GASTROINTESTINAL FUNCTION

中枢神经系统对胃肠功能的控制

• 批准号: 6052501
• 负责人: Richard Alan Gillis
• 金额: $ 6.36万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6052501
• 关键词: central neural pathway /tract; choline acetyltransferase; dorsal motor nucleus; electrophysiology; gastrointestinal function; innervation; interneurons; laboratory rat; membrane potentials; motor neurons; neural information processing; neural transmission; neuroregulation; single cell analysis; solitary tract nucleus; tissue /cell culture; tyrosine 3 monooxygenase; vagus nerve; voltage /patch clamp

This proposal sets forth plans for the study of the dorsal motor nucleus of the vagus (DMV), the single most important group of neurons in the brain for the control of gastrointestinal (G.I.) function. To understand how the brain exerts control over G.I. function, it is mandatory to understand how neurons in the DMV "operate" in terms of their intrinsic membrane currents and in terms of how they respond to incoming signals, and convey specific information to targeted areas of the G.I. tract. During the previous grant we have used whole cell patch-clamp recordings of single DMV neurons of the rat brain slice preparation to document the presence and distribution of ionic currents, especially hyperpolarization- activated currents I/H and I/XIR, and how the electrophysiological properties of DMV neurons are influenced by neuroactive substances (e.g. TRH, 5-HT, nitric oxide, norepinephrine, nicotine). We have established the existence of a glutamatergic neural pathway from the commissural sub- nucleus of the nucleus tractus solitarius (comNTS), and are in the process of describing how the DMV receives incoming signals form blood-borne chemicals in the area postrema (AP). Studies proposed in this continuing renewal application will build on our thesis that neurons of the DMV are functionally heterogenous and this is largely due to the specific array of intrinsic membrane currents contained within them. Our recent work has documented that neurons in the medial aspect of the DMV exhibit a more than 2-fold faster firing rate than neurons in the lateral aspect of the DMV. The reason(s) for this, the significance of differences in firing rate in response to incoming signals, and the peripheral targets affected by "fast" and "slow" discharging DMV neurons will be explored. Our hypothesis is that the different firing rates is due to the non-uniform distribution of I/H, I/XIR and the after depolarization current, I/AHP, in the medial and lateral column neurons. Work of others suggests that the I/KATP channel is also distributed non-uniformly among DMV neurons, and our hypothesis is that this channel is associated with medial column DMV neurons rather than lateral column neurons, and the presence of the I/KATP channel determines whether DMV neurons respond to blood-borne substances such as glucose. While our proposal is focused on comparing the electrophysiological behavior of medial and lateral column DMV neurons, we will also compare DMV neurons containing both acetylcholine and dopamine in the medial column with neurons in the medial column and do not contain dopamine. Furthermore, DMV neurons that do not exist the brain with the vagus will be compared electrophysiologically with those DMV neurons that do exist the brain with the vagus. Finally, we will determine whether findings made from the in vitro brain slice preparation can be confirmed and extended in an in vivo rat model. Our overall goal is to understand how information processing occurs in the DMV, and to relate this knowledge to how the brain controls G.I. function in health and disease.

这一建议提出了研究背运动核的计划 迷走神经（DMV），在迷走神经中最重要的一组神经元。 脑控制胃肠道（G.I.）功能了解 大脑如何控制GI函数，则必须 了解DMV中的神经元如何在其内在的 膜电流以及它们如何响应传入信号， 并将具体信息传达给美军的目标区域道。 在上一次的资助中，我们使用了全细胞膜片钳记录技术， 的大鼠脑切片制备的单个DMV神经元，以记录 离子电流的存在和分布，特别是超极化- 激活电流I/H和I/XIR，以及电生理学 DMV神经元的特性受神经活性物质（例如， TRH、5-HT、一氧化氮、去甲肾上腺素、尼古丁）。我们建立 存在一个从连合亚神经通路， 孤束核（comNTS），并在这个过程中 DMV是如何从血液中接收到信号的 化学品在最后地区（AP）。本研究建议继续 更新应用将建立在我们的论文，DMV的神经元是 这主要是因为它的特殊性， 内在的膜电流包含在其中。我们最近的工作 记录了DMV内侧的神经元表现出更多的 比2倍更快的放电率比神经元在侧面的 车管所其原因，击发差异的重要性 对输入信号的反应速率，以及受影响的外围目标 通过“快”和“慢”放电DMV神经元将被探索。我们 假设是，不同的发射率是由于不均匀的 I/H、I/XIR和后去极化电流I/AHP的分布， 内侧柱和外侧柱神经元。其他人的工作表明， I/KATP通道也在DMV神经元之间不均匀分布， 我们的假设是，该通道与内侧柱DMV相关 神经元而不是侧柱神经元，以及I/KATP的存在 通道决定DMV神经元是否对血液传播的物质作出反应 例如葡萄糖。虽然我们的建议侧重于比较 电生理行为的内侧和外侧柱DMV神经元，我们 也将比较含有乙酰胆碱和多巴胺的DMV神经元 与内侧柱的神经元，不包含 多巴胺此外，DMV神经元不存在于大脑中， 迷走神经将与那些DMV神经元进行电生理学比较， 大脑和迷走神经确实存在最后，我们将确定 从体外脑切片制备中得到的发现可以被证实 并在体内大鼠模型中延伸。我们的总体目标是了解 信息处理如何在DMV中发生，并将这些知识 大脑是如何控制胃肠道的在健康和疾病中发挥作用。