CNS CONTROL OF GASTROINTESTINAL FUNCTION

这项建议提出了研究背侧运动核的计划。 迷走神经(DMV)，迷走神经最重要的一组神经元 胃肠控制用脑(G.I.)功能。要理解 大脑如何对G.I.功能施加控制，这是强制性的 了解DMV中的神经元是如何根据其固有的 膜电流以及它们对输入信号的响应方式， 并将特定信息传达到G.I.区域的目标区域。 在上一次资助中，我们使用了全细胞膜片钳记录 大鼠脑片的单个DMV神经元的制备以记录 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，以及电生理如何 DMV神经元的特性受神经活性物质的影响(如 TRH、5-羟色胺、一氧化氮、去甲肾上腺素、尼古丁)。我们已经确立了 连合亚区谷氨酸能神经通路的存在 孤束核(ComNTS)，并正在进行中 描述车管所如何接收来自血液传播的传入信号 最后区域的化学品(美联社)。本报告中建议的研究仍在继续 续签申请将基于我们的论点，即机动车管理局的神经元 功能异质性，这在很大程度上是由于特定的 包含在其中的固有膜电流。我们最近的工作是 研究证明，车管所内侧的神经元表现出更多的 放电速度比大脑外侧区神经元快2倍以上。 车管所。原因(S)，射击差异的意义 响应传入信号的速率以及受影响的外围设备目标 通过“快”和“慢”放电，我们将探索DMV神经元。我们的 假设不同的发射速率是由于不均匀的 I/H、I/XIR和后除极电流I/AHP的分布 内侧柱神经元和外侧柱神经元。其他人的研究表明， I/KATP通道在DMV神经元中的分布也不均匀。 我们的假设是，这个通道与内侧柱DMV有关 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有反应 比如葡萄糖。虽然我们的提案侧重于比较 内侧柱和外侧柱DMV神经元的电生理行为 还将比较同时含有乙酰胆碱和多巴胺的DMV神经元 在内侧柱中有神经元，并且不包含 多巴胺。此外，不存在于大脑中的DMV神经元 迷走神经将在电生理学上与DMV神经元进行比较 确实存在有迷走神经的大脑。最后，我们将确定是否 从体外脑片制备中得到的发现可以得到证实 并在活体大鼠模型中进行了扩展。我们的总体目标是了解 如何在机动车管理局进行信息处理，并将这些知识联系起来 大脑在健康和疾病中如何控制G.I.的功能。

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.