Respiratory Reflexes In Vitro

体外呼吸反射

• 批准号: 6638808
• 负责人: NICHOLAS M MELLEN
• 金额: $ 12.09万
• 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 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6638808
• 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（申请人的摘要）：调查肺部传入的影响 中央呼吸节奏产生电路的信号，玻璃体酮 大鼠脑干/脊髓制备，保留肺及其迷走神经 使用神经。在此准备中，基本的节奏产生电路 保留，可以通过慢慢的选择性激活来调节 适应机械感受器（SAR）。为了应对生理压力，这 玻璃体制备复制了SAR介导的频率的关键方面 体内获得的调节：1）到期期间的肺膨胀（E）延长E 并改变呼吸节奏的阶段（Breuer hering呼气反射； bhe）。 2）灵感期间的肺通货膨胀（i）缩短I（Breuer-Hering 灵感反射； BHI）。 3）SAR反馈会增加呼吸频率 肺在I 1500毫秒内膨胀。我们将：1）确定必需 使用SAR调制作为探针的节律性回路。 BHE被阻止 GABAA受体拮抗剂双culline，表明CV介导的抑制作用 反射是必需的。因为呼吸节奏是重置的，所以神经元 肺中期通货膨胀期间超极化包括节律神经元。 在通货膨胀诱导的过程中，神经元激发，未调制或弱极化 呼气延长是继电器神经元或提供调节输入的神经元 进行节奏的电路。这是分类的关键功能探测器 呼吸神经元，基于它们的射击模式和内在的 属性，已抵抗简单，一致的分类。 2）表征 呼吸频率调节的细胞和突触机制。 根据刺激阶段，通货膨胀可以增加或减少呼吸系统 频率。此外，对SAR传入输入的响应既快速又有一个 慢组件。与这些观察结果一致的是一个假设 呼气延长是由于超极化通过pacisynaptic途径引起的 有节奏的灵感神经元的子集，而增加 伴随阶段通胀的频率是由于重组 呼吸网络。我们提出了测试这两个组成部分的实验 假设。 3）描述感觉反馈如何转化网络属性 髓回路。在网络级别，重新融合适当 感觉反馈大大增加了呼吸频率。在单曲 神经元水平，呼吸道调节神经元的发射模式被转化。 观察到的变化揭示了体外的节奏电路如何 完整动物的功能。