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(申请人摘要)：研究肺传入的影响 中央呼吸节律产生电路上的信号，在玻璃体中 大鼠脑干/脊髓准备，保留肺及其迷走神经 使用的是神经支配。在这个准备过程中，基本的节奏产生电路 被保留，并可被选择性地缓慢激活的肺调节 适应机械感受器(SAR)。为了应对生理压力，这 在试管准备中复制了SAR介导的频率的关键方面 在体内获得的调制：1)呼气时肺充气(E)延长E 并改变呼吸节律的相位(Breuer-Hering呼气反射； BHE)。2)吸气时的肺膨胀(I)缩短I(Breuer-Hering 吸气反射；BHI)。3)合成孔径雷达反馈增加呼吸频率 肺部在发病后1500毫秒内充气。我们将：1)确定基本要素 以合成孔径雷达调制为探头的节律电路。BHE被屏蔽了 GABAA受体拮抗剂荷包牡丹碱，表明CV介导的抑制作用 是反射所必需的。因为呼吸节律被重置，神经元 呼气中期充气时的超极化包括节律性神经元。 充气诱导期间神经元兴奋、未调制或微弱超极化 呼气延长是中继神经元，或提供调制输入的神经元 到有节奏的回路。这是一个关键的功能探测器，可以分类 呼吸神经元，基于它们的放电模式和固有的 属性，已经抵制了简单、一致的分类。2)描述 呼吸频率调节的细胞和突触机制。 根据刺激阶段的不同，通货膨胀会增加或减少呼吸。 频率此外，对SAR传入输入的反应既快又快 慢速部件。与这些观察结果相一致的是这样一个假设 呼气延长是通过少突触通路的超极化所致 节律性吸气神经元的子集，而增加的 伴随相位性膨胀的频率是由于 呼吸系统。我们建议进行实验来测试这两个组成部分 假设。3)描述感觉反馈如何改变网络属性 延髓环路。在网络层面，适当地重组 感觉反馈极大地增加了呼吸频率。在单曲中 神经元水平、呼吸调节神经元的放电模式发生了变化。 观察到的变化揭示了体外节律回路是如何 在完好无损的动物身上发挥作用。