Vestibular Regulation of Respiratory Muscle Activity

呼吸肌活动的前庭调节

• 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
• 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

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）：呕吐是膈肌和腹肌共同收缩的定型模式的结果，产生高胃内压。本申请的目的是破译产生呕吐的延髓回路对前庭输入的处理，并确定这种信号处理如何受到其他可能引起呕吐的输入的影响。具体目标1将绘制在前庭受体刺激引起的呕吐和伴随的恶心期间激活的神经元的位置，并将这些部位与胃肠道（GI）输入触发的呕吐期间激活的部位进行比较。具体目标2将采用前庭核（VN）的亚区失活，以确定该地区是必不可少的产生前庭诱发呕吐。一旦包含参与产生呕吐的神经元的脑干区域被建立，随后的实验将确定这些区域中的细胞对添加到GI受体激活的自然前庭刺激的反应。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GI和精氨酸输入，这些输入可诱导呕吐和恶心。特定目标4A将确定作为呕吐模式发生器的组成部分的区域中的神经元的反应：位于NTS和面后核之间的背侧延髓外侧被盖区（LTF）。具体目标4 B将考虑PBN对信号的处理，PBN参与将内脏感觉信号传递到前脑，以深入了解前庭和内脏输入在该区域的整合如何不同，该区域对于产生恶心和产生呕吐的髓质元素至关重要。在目标4的结论中，我们将对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的神经元对鸟氨酸刺激的反应进行彻底采样。我们还将系统地确定前庭信号是如何在呕吐回路中转换的，因为它们从VN中继到NTS，最后到LTF和PBN。此外，我们还将确定其他呕吐信号的存在如何影响肾上腺素输入的处理，以及这种处理是否在呕吐发作之前或之后立即发生了深刻的改变。因此，这些研究将提供对负责产生晕动病的信号整合的见解。 公共卫生相关性：呕吐是非常重要和常见的临床问题。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、飞机和航天器旅行期间。晕动病是与前庭系统有关的最常见疾病，但脑干神经元对前庭信号的处理触发和协调呕吐的机制却知之甚少。拟议的实验包括第一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种处理;因此，这项工作将为产生呕吐的机制提供基本的新见解。