Network mechanisms for respiratory rhythm generation

呼吸节律产生的网络机制

• 批准号: 6822022
• 负责人: NICHOLAS M MELLEN
• 金额: $ 22.05万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 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 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6822022
• 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 (provided by applicant): New evidence indicates that two mechanistically distinct, spatially separate networks can independently generate respiratory rhythm. We propose that the two networks in concert meet the conflicting demands of adaptive-ness and robustness required for the maintenance of blood-gas homeostasis. This new finding puts emphasis on the role of network interactions in rhythm generation. Because preparations currently available allow easy access to neurons but are too reduced (transverse slice preparation), or retain the networks of interest but do not allow easy access to them (en bloc preparation), we have developed a tilted saggital slice preparation that retains the networks present en bloc but affords good access to the networks of interest. We used optical recordings using a membrane permeable Ca++ indicator to determine the best parameters for cutting the slice, and use optical recording techniques routinely to monitor local network activity along the column of respiration modulated neurons in ventrolateral medulla that are exposed at the surface of the saggital slice. We will use optical signals to identify 2 classes of endogenously bursting respiratory neurons for detailed investigation using intracellular recording techniques. These endogenous bursters differ in that one population changes its bursting frequency as a function of membrane potential (voltage-dependent endogenous burster; VDEB), while the other does not (voltage-independent endogenous burster; VIEB). Due to this difference, VDEB cycle period can be altered by transient de- or hyperpolarizing impulses; while VIEBs will be less sensitive to such inputs. This provides a mechanism for our hypothesis; we propose that VDEBs mediate cycle-to-cycle adaptiveness to respiratory rhythm-generating networks, while VIEBs maintain network stability by rapidly restoring baseline rhythm. We propose to test this hypothesis at the network level, by selectively modulating VIEB and VDEB networks, and at the single neuron level, by characterizing perturbation responses in synaptically isolated VIEBs and VDEBs.

描述（由申请人提供）：新证据表明两个机械上不同、空间上分离的网络可以独立产生呼吸节律。我们建议这两个网络共同满足维持血气稳态所需的适应性和鲁棒性的相互冲突的需求。这一新发现强调了网络交互在节奏生成中的作用。由于目前可用的准备工作可以轻松访问神经元但过于减少（横向切片准备），或者保留感兴趣的网络但不允许轻松访问它们（整体准备），我们开发了一种倾斜矢状切片准备，保留了网络整体存在，但提供对感兴趣网络的良好访问。我们使用透膜 Ca++ 指示剂进行光学记录，以确定切割切片的最佳参数，并常规使用光学记录技术来监测暴露在矢状表面的腹外侧髓质中呼吸调节神经元柱的局部网络活动片。我们将使用光信号来识别两类内源性爆发呼吸神经元，以便使用细胞内记录技术进行详细研究。这些内源性爆发的不同之处在于，一个群体将其爆发频率作为膜电位的函数改变（电压依赖性内源性爆发；VDEB），而另一群体则不改变其爆发频率（电压无关的内源性爆发；VIEB）。由于这种差异，VDEB 循环周期可以通过瞬态去极化或超极化脉冲来改变；而 VIEB 对此类投入不太敏感。这为我们的假设提供了一种机制；我们认为 VDEB 介导呼吸节律生成网络的周期适应性，而 VIEB 通过快速恢复基线节律来维持网络稳定性。我们建议通过选择性地调节 VIEB 和 VDEB 网络在网络水平上检验这一假设，并在单个神经元水平上通过表征突触隔离的 VIEB 和 VDEB 中的扰动反应来检验这一假设。