Respiratory Reflexes In Vitro

体外呼吸反射

• 批准号: 6538067
• 负责人: NICHOLAS M MELLEN
• 金额: $ 21.47万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2004-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6538067
• 关键词: biological clocks; brain electrical activity; brain stem; intracellular; laboratory rat; mechanoreceptors; neurons; newborn animals; pulmonary respiration; respiratory reflex; spinal cord; vagus nerve

DESCRIPTION (Applicant's abstract): To investigate the effect of lung afferent signals on central respiratory rhythm generating circuits, an in vitroneonate rat brainstem/spinal cord preparation, retaining the lungs and their vagal innervation is used. In this preparation, essential rhythm generating circuits are retained, and can be modulated by selective activation of lung slowly adapting mechanoreceptors (SAR). In response to physiological pressures, this in vitropreparation replicates critical aspects of SAR-mediated frequency modulation obtained in vivo: 1) Lung inflation during expiration (E) prolongs E and shifts the phase of respiratory rhythm (Breuer-Hering expiratory reflex; BHE). 2) Lung inflation during inspiration (I) shortens I (Breuer-Hering inspiratory reflex; BHI). 3) SAR feedback increases respiratory frequency when lungs are inflated within 1500 ms of I onset. We will: 1) Identify essential rhythmogenic circuits using SAR modulation as a probe. The BHE is blocked by GABAA receptor antagonist bicuculline, indicating that CV-mediated inhibition is necessary for the reflex. Because the respiratory rhythm is reset, neurons hyperpolarized during mid-expiratory inflation include rhythmogenic neurons. Neurons excited, unmodulated or weakly hyperpolarized during inflation-induced expiratory lengthening are relay neurons, or neurons providing modulatory input to rhythmogenic circuits. This is a critical functional probe to classify respiratory neurons, which based on their firing patterns and intrinsic properties, have resisted simple, consistent classification. 2) Characterize the cellular and synaptic mechanisms for respiratory frequency modulation. Depending on the stimulus phase, inflation can increase or decrease respiratory frequency. In addition, response to SAR afferent input has both a fast and a slow component. Consistent with these observations is the hypothesis that expiratory lengthening is due to hyperpolarization via a paucisynaptic pathway of a subset of rhythmogenic inspiratory neurons, while the increase in frequency accompanying phasic inflation is due to a reorganization of the respiratory network. We propose experiments to test both components of this hypothesis. 3) Describe how sensory feedback transforms the network properties of medullary circuits. At the network level, reincorporating appropriate sensory feedback dramatically increases respiratory frequency. At the single neuron level, firing patterns of respiratory-modulated neurons are transformed. The observed changes shed light on how rhythmogenic circuits in vitro may function in the intact animal.

描述（申请人摘要）：研究肺传入神经的作用 中枢呼吸节律产生电路上的信号， 大鼠脑干/脊髓制备，保留肺及其迷走神经 使用神经支配。在这个准备过程中，基本的节奏产生电路 保留，并可通过选择性激活肺缓慢调节 适应性机械感受器（SAR）。为了应对生理压力， 体外制备复制了SAR介导频率的关键方面 在体内获得的调节：1）呼气期间的肺膨胀（E） 并使呼吸节律的时相（Breuer-Hering呼气反射; BHE）。2)吸气时的肺膨胀（I）缩短了I（Breuer-Hering 吸气反射; BHI）。3)SAR反馈增加呼吸频率， 肺在I开始的1500毫秒内膨胀。我们将：（1）确定必要的 使用SAR调制作为探针的节律电路。BHE被以下物质堵塞 GABAA受体拮抗剂荷包牡丹碱，表明CV介导的抑制 是反射所必需的。因为呼吸节律被重置，神经元 在呼气中期膨胀期间超极化的神经元包括节律性神经元。 神经元兴奋，未调制或弱超极化在通货膨胀诱导 呼气延长是中继神经元，或提供调节输入的神经元 到节律电路这是一个关键的功能探针， 呼吸神经元，基于其放电模式和内在的 属性，抵制简单，一致的分类。2)表征 呼吸频率调制的细胞和突触机制。 根据刺激阶段，充气可以增加或减少呼吸 频率.此外，对SAR传入输入的反应既有快速的， 慢分量与这些观察相一致的假设是， 呼气延长是由于通过少突触通路的超极化 的一个子集的节律性吸气神经元，而增加 伴随阶段性膨胀的频率是由于 呼吸网络我们提出实验来测试这两个组成部分， 假说. 3)描述感觉反馈如何改变网络属性 脊髓回路的结构。在网络一级， 感觉反馈显著增加呼吸频率。在单 在神经元水平上，转换了经调制的神经元的放电模式。 观察到的变化揭示了体外节律性回路如何 在完整的动物中发挥作用。