Integration by Airway Parasympathic Ganglia Neurons

气道副交感神经节神经元的整合

基本信息

批准号：
6737461
负责人：
ALLEN C MYERS
金额：
$ 32.7万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1992
资助国家：
美国
起止时间：
1992-04-01 至 2006-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6737461
关键词：
acetylcholine autonomic ganglion bronchus bronchus circulation guinea pigs human tissue muscle tone neurons neuroregulation neurotransmitter transport nitric oxide parasympathetic nervous system smooth muscle substance K substance P trachea vasoactive intestinal peptide

项目摘要

In the airway, the autonomic nervous system controls smooth muscle tone, secretion by glands, and blood flow. Although there is abundant physiological and pharmacological evidence indicating that dysfunction of this autonomic control of the airways contributes to the causes and symptoms of pulmonary diseases such as bronchial asthma, chronic obstructive pulmonary disease and emphysema, little is actually known about the regulation of these nerves. Our long term goal is to provide knowledge of how autonomic tone is regulated in the airway, especially that provided by the parasympathetic nervous system. Control of smooth muscle in the trachea and bronchi is predominantly by nerve fibers that emanate from neuronal cell bodies in parasympathetic ganglia, small clusters of cell bodies located near the airway wall. The parasympathetic tone of the airway smooth muscle is thought to be under the control of the central nervous system where signals are transmitted rhythmically during respiration to the parasympathetic neurons in the airway wall. This signal activates airway parasympathetic ganglia neurons by release of a neurotransmitter which mediates cholinergic synaptic transmission in the ganglia. Separate, but potentially important, forms of neural regulation of parasympathetic neurons in the airways are by the so-called local peripheral reflex pathway and the intraganglionic pathways. In the peripherals reflex pathway, a sensory nerve is activated by changes in the airway and communicates directly with the parasympathetic neuron in the nearby ganglia by releasing neuropeptides from branches of the sensory axon, evoking non-cholinergic synaptic transmission. In other words, this is an sensory- parasympathetic reflex, independent of the central nervous system. A peripheral reflex would thus allow local increases in parasympathetic tone in an airway segment, independent of changes in another segment. In the intraganglionic pathway, postganglionic axons leaving a bronchial ganglion serve to innervate, and modulate the function of neighboring ganglia within the airway tree. This proposal describes experiments that will address our central hypothesis, namely that the parasympathetic nerve activity in the airways is shaped by the integration of three separate inputs: 1.) input from the central nervous system {classical cholinergic nicotinic input), 2.) input from the peripheral reflex sensory fibers, and 3.) input from surrounding postganglionic parasympathetic ganglia. We feel that an understanding of the mechanism of this integration is a prerequisite to obtaining knowledge on the mechanisms by which airway neurophysiology is regulated in health and disregulated in disease.

在气道中，自主神经系统控制平滑肌张力，腺体分泌和血流。尽管有大量的生理和药理证据表明，这种对气道的自主神经控制功能障碍导致了肺部疾病的原因和症状，例如支气管哮喘，慢性阻塞性肺部疾病和肺气肿，但实际上对这些神经的调节几乎没有知识。我们的长期目标是提供有关如何在气道中调节自主语调的知识，尤其是副交感神经系统提供的自主基调。控制气管和支气管中平滑肌的控制主要是由神经元细胞体散发出副交感神经的神经元细胞体的神经纤维，这是位于气道壁附近的小细胞体。气道平滑肌的副交感神经声被认为是在中枢神经系统的控制之下，在中枢神经系统中，信号在气道壁上的副交感神经元呼吸时会节奏传播。该信号通过释放神经递质介导神经节中的胆碱能突触传递来激活气道副交感神经神经元。所谓的局部外围反射途径和旁膜内途径是单独但可能重要的，气道中副交感神经元的神经调节形式。在外围物反射途径中，气道的变化激活了感觉神经，并通过从感觉轴突的分支中释放神经肽直接与附近神经节中的副交感神经元进行通信，引起了非胆碱能突触传播。换句话说，这是一种与中枢神经系统无关的感觉 - 副交感神经反射。因此，外围反射将允许气道段中的副交感神经音调局部增加，而与另一段的变化无关。在神经节途径中，留下支气管神经节的后轴突可支配，并调节气道树内相邻神经节的功能。该提案描述了将解决我们中心假设的实验，即，气道中的副交感神经活动是通过三个单独输入的整合来塑造的：1。）来自中枢神经系统（经典胆碱能烟气输入的经典胆碱能输入），2。2。）。我们认为，对这种整合机制的理解是获得有关在健康中调节气道神经生理学机制并在疾病中不受调控的机制的知识的先决条件。