NEURAL CONTROL OF VENTILATION AND AROUSAL

通气和唤醒的神经控制

• 批准号: 3356653
• 负责人: ALFRED P FISHMAN
• 金额: $ 21.01万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1993-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3356653
• 关键词: aquatic organism; autoradiography; brain mapping; decerebration; electrophysiology; evolution; fish; histochemistry /cytochemistry; hormone receptor; microinjections; motor neurons; neural information processing; neural initiation; neuroanatomy; neurochemistry; neuropeptides; nontherapeutic iontophoresis; pulmonary circulation; pulmonary respiration; respiration regulatory center; respiratory muscles; species difference; thyrotropin releasing hormone; vagus nerve

Understanding the basis of dyspnea and the mechanisms that produce apnea requires knowledge of the neural circuits that control the breathing rhythm. Currently, however, the neural mechanisms that are the basis for respiration are uncertain. The current investigative approach is primarily a reductionist one. This is based on the concept that the neural circuits involved can be unravelled if the component parts are identified as well as how they interact. The obvious difficulty of this approach leads to consideration of alternative strategies. One such approach is to develop an understanding of the evolution of the respiratory pattern generator by studying its behavior in more primitive species and then following its development. This has led other to extensive study of the pattern generator for gill ventilation in lampreys and fish. But there is no proof that the mammalian respiratory pattern generator and that for gill ventilation are related. The presence of both pulmonary and gill ventilation in species such as the lungfish challenge this concept. In preliminary studies it has been demonstrated that the response characteristics of the circuits controlling pulmonary ventilation in the lungfish have many of the same features as in mammals. Thus study of neural control of ventilation in this species seems a more appropriate starting point for investigation of the evoluntionary development of the respiratory pattern generator. An additional advantage of the species is that its central nervous system contains high concentrations of TRH thereby facilitating study of the role of this neuropeptide in respiratory neural control. Thus, the aims of this proposal are to establish the response characteristics of the pattern generators for both pulmonary and gill ventilation so as to relate these to those described for lamprey and mammals. The neural mechanisms mediating these rhythms will be studied by both extracellular recording of neuronal activity and by intracellular recording of synaptic input into respiratory motoneurons. This will permit concepts to be developed as to how respiratory rhythm is generated and serve as a focus for comparison to other species. The electro-physiology studies will be complimented by study of the role of TRH in respiratory rhythmogenesis. Neurophysiological results will be related to those from neuroanatomical studies on the distribution of receptors for TRH and TRH-containing neurons. The hypothesis that TRH mediates its effect on respiration by causing alterations in state will be studied by taking advantage of the natural state of dormancy - estivation.

了解呼吸困难的基础和机制 产生呼吸暂停需要了解神经回路 控制呼吸节奏。 但是，目前是神经 作为呼吸基础的机制尚不确定。 这 当前的调查方法主要是一种还原论者。 这是基于所涉及的神经回路可以的概念 如果确定组件零件以及如何弄清楚 他们互动。 这种方法的明显困难导致 考虑替代策略。 一种这样的方法是 对呼吸道的演变有一种理解 图案发生器通过研究其行为以更原始 物种，然后遵循其发展。 这导致了其他 大量研究用于g的模式发生器 七lamp和鱼。 但是没有证据表明哺乳动物 呼吸模式发生器，用于g的通风是 有关的。 肺和g的存在 诸如肺鱼等物种挑战了这个概念。 在初步 研究已经证明了响应特征 控制肺鱼中肺通风的电路 具有与哺乳动物相同的许多特征。因此研究 该物种中通风的神经控制似乎更多 适当的起点用于调查进化 呼吸模式发生器的开发。 另一个 该物种的优势是其中枢神经系统 包含高浓度的TRH，从而促进 该神经肽在呼吸神经控制中的作用。 因此， 该提议的目的是建立回应 肺和肺部模式发生器的特征 g的通风以将其与所描述的那些相关 七lamp和哺乳动物。 介导的神经机制 将通过两种细胞外记录来研究节奏 神经元活性和通过细胞内记录突触输入 进入呼吸运动神经元。 这将使概念成为 开发了如何产生呼吸节奏并用作 与其他物种进行比较的重点。 电体生理学 研究将通过研究TRH在 呼吸节律发生。 神经生理结果将是 与分布的神经解剖学研究有关 用于TRH和TRH神经元的受体。 这 TRH通过引起介导其对呼吸的影响的假设 通过利用 自然休眠状态 - 审查。