BRAINSTEM CIRCUITS CONTROLLING GASTROINTESTINAL FUNCTION

形态特征：孤束核和背侧核。 迷走神经运动核(DMV)是电路的重要组成部分 负责迷走-迷走神经反射的协调，如胃 接受性放松和回肠制动。最近，有人提出了 有一些谨慎的节点，从那里传递感官信息 NTS中的特定神经元分布于不同的DMV神经元群。尽管 这一概念已经被一些调查人员讨论和检验， 没有电生理学证据支持它，可能是因为 与任何活体实验相关的重大技术困难 这将试图确定单个NT和 DMV神经元。另一方面，切片范例非常适合这一点 调查类型。我们在本申请中描述的研究包括 基于以下假设：假设1：NTS-DMV电路是 以允许NTS中的特定神经元相互作用的方式组织 在车管所里有选定的神经细胞亚群。特别是，我们建议 内侧DMV的神经元接受来自 中枢神经系统(一种相互作用，可以为 感受性松弛反射)，而外侧DMV中的神经元接受 “延缓或持续时间较长的抑制性输入来自大脑中隔核神经元(AN)” 可在回肠制动现象中发挥作用的相互作用)。 假设2：延髓中缝核整合胃肠反射活动 提供对NTS-DMV突触的选择性调制。现建议： 这种调制是由中缝髓神经元完成的，该神经元兴奋 DMV神经元的子集和/或通过 释放5-羟色胺、TRH和/或SP。这些假说将使用完整的 脑干切片中的细胞膜片钳记录，包括NTS， 车管所和中缝核团。这些切片将取自有 在分离的分支中放置荧光示踪剂 隔下迷走神经或胃肠道的部分区域。这 协议将标记内脏传入终末的子集 终末终止于NTS神经元和DMV神经元的胞体投射 到接受荧光注射的胃肠道区域 追踪剂。突触电流和电位将从NTS和 将被记录在DMV和/或NTS中；DMV-NTS突触的调制 将在刺激邻近的中缝髓核和 用5-羟色胺、TRH和/或SP灌流。通过追踪这些数据获得的数据 特定的目的将揭示潜在的突触电流的行为 离散的NTS和DMV神经元群体。此外，根本的 迷走神经反射的回路将被阐明。这些数据将 加深我们对NTS和DMV之间的相互作用的理解 神经元可以导致神经元活动控制的模式 迷走神经反射，如胃容受性松弛和回肠制动。

DESCRIPTION: The nucleus of the tractus solitarius (NTS) and the dorsal motor nucleus of the vagus (DMV) are essential components of a circuit responsible for the coordination of vago-vagal reflexes such as gastric receptive relaxation and the ileal brake. Recently, it has been proposed that there are discreet nodes where sensory information is transmitted from specific neurons in the NTS to distinct populations of DMV neurons. Though this concept has been discussed and examined by a number of investigators, there is no electrophysiologic evidence to support it, likely because of substantial technical difficulties associated with any in vivo experiments that would attempt to determine the interactions between individual NTS and DMV neurons. On the other hand, slice paradigms are ideally suited to this type of investigation. The studies we describe in this application are based on the following hypotheses: Hypothesis 1: The NTS-DMV circuitry is organized in a manner that allows specific neurons in the NTS to interact with selected neuronal subsets in the DMV. In particular, we propose that neurons in the medial DMV receive a fast excitatory input from neurons in the cen-NTS (an interactions that could provide the anatomical substrate for the receptive relaxation reflex), while neurons in the lateral DMV receive a "slower or longer lasting inhibitory input from neurons in the com-NTS (an interaction that could play a role in the ileal brake phenomenon). Hypothesis 2: The medullary raphe nuclei integrate GI reflex activity by providing a selective modulation of NTS-DMV synapses. It is proposed that this modulation is accomplished by medullary raphe neurons that excite of subset of DMV neurons and/or inhibit a subpopulation of NTS neurons via the release of 5-HT, TRH and/or SP. The hypotheses will be tested using whole cell patch clamp recordings in brainstem slices that include the NTS, the DMV and the raphe nuclei. The slices will be taken from rats that have undergone placement of fluorescent tracers in isolated branches of the subdiaphragmatic vagus nerve or select regions of the GI tract. This protocol will label a subset of the terminals of visceral afferents that terminate on NTS neurons as well as the somata of DMV neurons that project to the region of the GI tract that received the injection of the fluorescent tracer. Synaptic currents and potentials will be evoked from the NTS and will be recorded in DMV and/or NTS; the modulation of the DMV-NTS synapses will be analyzed upon stimulation of the adjacent raphe medullary nuclei and upon perfusion with 5-HT, TRH and/or SP. Data obtained from pursuing these specific aims will reveal the synaptic currents underlying the behavior of discrete NTS and DMV neuronal populations. Furthermore, the fundamental circuitry of the vago-vagal reflex will be elucidated. These data will increase our understanding of how the interaction between NTS and DMV neurons can result in the pattern of neuronal activity controlling vago-vagal reflexes such as gastric receptive relaxation and ileal brake.