Multisensory Integration Producing Nausea and Vomiting

项目摘要/摘要： 几十年来，人们一直认为，尽管触发了刺激，但同样的脑干区域负责 引起恶心和呕吐。然而，我们最近的初步研究表明，恶心和呕吐 是复杂的情况，包括各种不同的生理反应，这些反应因个体而异，在 与触发刺激相一致。这笔赠款使用协同方法来描述分歧， 前庭和其他由脑干神经元汇聚和多感觉整合的信号可以产生 复仇女神。具体目标1包括第一次对参与的脑干通路进行全面比较 胃内注射硫酸铜或出现前庭症状后出现恶心和呕吐 引起晕动病的刺激。通过利用我们最近开发的创新统计方法，我们 将从Fos标记模式中识别由这些刺激激活的神经网络。我们假设 不同的脑干网络参与动物胃部肌电的客观变化 刺激前庭和胃肠感受器后出现恶心的活动。具体目标2 和3分别使用神经生理学技术来表征呕吐输入的整合 臂旁核(PBN)神经元将这些信号传递到幕上脑区，并通过 迷走神经背核及其附近的副交感节前神经元(PPGN) 将信号传递给外周效应器的疑核。目标3还将比较以下几个方面的反应 在整合这些信号方面发挥关键作用的两个相邻区域的神经元的PPGN：束核 孤立区(NTS)和构成脑干“呕吐中心”的外侧被盖区(LTF)。目标3 结合了对前庭刺激PPGNS的反应的第一个表征；尽管这些神经元 在呕吐过程中协调胃肠活动的变化，几乎对修饰一无所知 由催吐性刺激引起的射击率。通过对比来自前庭和前庭的输入的整合 这些关键脑干神经元群(PPGN和PBN、NTS和LTF)的胃肠传入纤维， 我们可以检验我们的总体假设，即引发呕吐的信号在脑干中独立处理， 而且只汇聚在直接控制呕吐反应的神经元上。了解前庭和前庭如何 胃肠信号在脑干呕吐通路中的转换是产生对新的 治疗恶心和呕吐。在拟议的研究结束时，我们将识别出脑干 调节恶心和呕吐的网络，恶心相关和呕吐信号对活动的影响 以及它们对前庭和/或前庭的差异和/或协同反应 胃肠道信号。

Project Summary/Abstract: For decades, it has been assumed that despite the triggering stimulus, the same brainstem areas are responsible for producing nausea and emesis. However, our recent preliminary studies suggested that nausea and vomiting are complex conditions that include a variety of physiological responses that vary between individuals, and in accordance with the triggering stimulus. This grant uses synergistic approaches to characterize the divergence, convergence, and multisensory integration by brainstem neurons of vestibular and other signals that can produce emesis. Specific Aim 1 includes the first comprehensive comparison of the brainstem pathways that participate in generating nausea and emesis following the intragastric infusion of copper sulfate or presentation of vestibular stimuli to induce motion sickness. By utilizing an innovative statistical approach that we recently developed, we will identify the neural networks that are activated by these stimuli from Fos labeling patterns. We hypothesize that different brainstem networks are engaged in animals that exhibit objective changes in stomach myoelectric activity indicative of nausea following stimulation of vestibular versus gastrointestinal receptors. Specific Aims 2 and 3 respectively use neurophysiologic techniques to characterize the integration of emetic inputs by parabrachial nucleus (PBN) neurons that transmit these signals to supratentorial brain areas, and by parasympathetic preganglionic neurons (PPGNs) in the dorsal motor nucleus of the vagus (DMV) and near-by nucleus ambiguus that transmit the signals to peripheral effectors. Aim 3 will also compare the responses of PPGNs to those of neurons in two adjacent areas that play a key role in integrating these signals: nucleus tractus solitarii (NTS) and the lateral tegmental field (LTF), which comprises the brainstem “vomiting center.” Aim 3 incorporates the first characterization of responses to vestibular stimulation of PPGNs; although these neurons coordinate the changes in gastrointestinal activity during vomiting, virtually nothing is known about modifications in their firing rate elicited by emetic stimuli. By contrasting the integration of inputs from vestibular and gastrointestinal afferents in these key groups of brainstem neurons (PPGNs and those in PBN, NTS, and LTF), we can test our overall hypothesis that signals that elicit vomiting are processed independently in the brainstem, and only converge on neurons that directly control emetic responses. Understanding how vestibular and gastrointestinal signals are transformed in brainstem emetic pathways is key to generating insights into new treatments for nausea and vomiting. At the conclusion of the proposed studies, we will have identified brainstem networks that mediate nausea and vomiting, the influences of nausea-related and emetic signals on the activity of neurons in those networks, and their differential and/or synergistic responsiveness to vestibular and gastrointestinal signals.