Vestibular Regulation of Respiratory Muscle Activity

呼吸肌活动的前庭调节

基本信息

批准号：
8230748
负责人：
Carey David Balaban
金额：
$ 35.61万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-05-01 至 2015-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8230748
关键词：
Abbreviations Abdomen Abdominal Muscles Acceleration Affect Affective Agonist Anesthesia procedures Area Behavior Brain Stem Cell Nucleus Cells Chemotherapy-Oncologic Procedure Clinical Complex Copper Sulfate Disease Dorsal Elements Emetics Environment FOS Protein Fast Blue Funding Generations Goals Grant Head Hypothalamic structure Inferior Labyrinth Lateral Limbic System Link Location Maps Mechanoreceptors Medial Military Personnel Motion Sickness Motor Motor Neurons Muscimol Nausea Nausea and Vomiting Neural Pathways Neurons Nucleus solitarius Pathway interactions Patients Pattern Poisoning Population Positioning Attribute Process Property Prosencephalon Recovery Regulation Research Respiratory Diaphragm Respiratory Muscles Reticular Formation Role Sampling Signal Transduction Site Spacecraft Stereotyping Stimulus Stomach Structure of area postrema System Techniques Tracer Training Travel Vestibular nucleus structure Viscera Visceral Vomiting Work computerized data processing gastrointestinal insight irritation neural circuit neuromechanism novel therapeutics parabrachial nucleus pressure public health relevance receptor research study respiratory response virtual

项目摘要

DESCRIPTION (provided by applicant): Vomiting is a consequence of a stereotyped pattern of co-contractions of the diaphragm and abdominal muscles that generate high intragastric pressures. The goal of this application is to decipher the processing of vestibular inputs by the medullary circuitry that produces vomiting, and to determine how this signal processing is affected by other inputs that can elicit emesis. Specific Aim 1 will map the locations of neurons activated during vomiting and accompanying nausea elicited by stimulation of vestibular receptors and compare the sites to those activated during emesis triggered by gastrointestinal (GI) inputs. Specific Aim 2 will employ inactivation of subregions of the vestibular nuclei (VN) to identify the area that is essential for producing vestibular-elicited vomiting. Once the brainstem regions containing neurons that participate in generating vomiting are established, subsequent experiments will ascertain the responses of cells in these areas to natural vestibular stimulation added to activation of GI receptors. Specific Aim 3 will consider neuronal responses in nucleus tractus solitarius (NTS) and the VN, which respectively receive GI and labyrinthine inputs from the periphery that can induce emesis and nausea. Specific Aim 4A will determine the responses of neurons in a region that is a component of the vomiting pattern generator: the dorsal medullary lateral tegmental field (LTF) positioned between NTS and the retrofacial nucleus. Specific Aim 4B will consider the processing of signals by PBN, which is involved in transmitting viscerosensory signals to the forebrain, to provide insights into how integration of vestibular and visceral inputs together differs in this region critical for generating nausea and medullary elements that produce vomiting. At the conclusion of Aim 4 we will have thoroughly sampled the responses of neurons to labyrinthine stimulation in the major brainstem areas known to participate in triggering and coordinating vomiting and accompanying affective responses. We will also systematically determine how vestibular signals are transformed in the emetic circuit as they are relayed from the VN to NTS and finally to LTF and the PBN. Furthermore, we will ascertain how the presence of other emetic signals affects the processing of labyrinthine inputs, and whether this processing is profoundly altered immediately before or after an episode of vomiting. As such, the studies will provide insights into the signal integration responsible for the generation of motion sickness. PUBLIC HEALTH RELEVANCE: Vomiting is highly significant and common clinical problem. Nausea and vomiting can occur during poisoning, cancer chemotherapy, recovery from anesthesia, activities in virtual environments (including civilian and military training simulators), and travel in cars, airplanes, and spacecraft. Motion sickness is the most common malady linked with the vestibular system, but the processing of vestibular signals by the brainstem neurons that trigger and coordinate emesis is poorly understood. The proposed experiments comprise the first systematic study of how vestibular signals are transformed by the neural pathways that trigger and coordinate vomiting and will also ascertain how inputs from the viscera affect this processing; as such, the work will provide fundamental new insights into the mechanisms that generate vomiting.

描述（由申请人提供）：呕吐是横膈膜和腹部肌肉共同收缩的刻板模式的结果，这种模式会产生高胃内压力。该应用的目标是破译产生呕吐的髓质电路对前庭输入的处理，并确定该信号处理如何受到其他可引起呕吐的输入的影响。具体目标 1 将绘制前庭受体刺激引起的呕吐和伴随恶心期间激活的神经元的位置，并将这些位置与胃肠道 (GI) 输入触发的呕吐期间激活的位置进行比较。具体目标 2 将采用前庭核 (VN) 子区域的失活来识别对于产生前庭诱发呕吐至关重要的区域。一旦建立了包含参与产生呕吐的神经元的脑干区域，后续实验将确定这些区域的细胞对自然前庭刺激以及胃肠道受体激活的反应。具体目标 3 将考虑孤束核 (NTS) 和 VN 中的神经元反应，它们分别接收来自外周的胃肠道和迷路输入，从而引起呕吐和恶心。具体目标 4A 将确定呕吐模式发生器组成部分区域中神经元的反应：位于 NTS 和面后核之间的背髓外侧被盖区 (LTF)。具体目标 4B 将考虑 PBN 对信号的处理，PBN 涉及将内脏感觉信号传输到前脑，以深入了解前庭和内脏输入的整合在该区域中如何不同，这对于产生恶心和产生呕吐的髓质成分至关重要。在目标 4 结束时，我们将彻底采样已知参与触发和协调呕吐以及伴随的情感反应的主要脑干区域中神经元对迷路刺激的反应。我们还将系统地确定前庭信号如何在催吐回路中进行转换，因为它们从 VN 传递到 NTS，最后传递到 LTF 和 PBN。此外，我们将确定其他催吐信号的存在如何影响迷路输入的处理，以及这种处理是否在呕吐发作之前或之后立即发生深刻的改变。因此，这些研究将深入了解导致晕动病产生的信号整合。公共卫生相关性：呕吐是非常重要且常见的临床问题。恶心和呕吐可能发生在中毒、癌症化疗、麻醉恢复、虚拟环境中的活动（包括民用和军事训练模拟器）以及乘坐汽车、飞机和航天器旅行时。晕动病是与前庭系统相关的最常见疾病，但人们对脑干神经元触发和协调呕吐的前庭信号处理知之甚少。拟议的实验包括首次系统研究前庭信号如何通过触发和协调呕吐的神经通路进行转换，并将确定来自内脏的输入如何影响这一处理；因此，这项工作将为呕吐的产生机制提供基本的新见解。