Network mechanisms for respiratory rhythm generation

呼吸节律产生的网络机制

• 批准号: 7244312
• 负责人: NICHOLAS M MELLEN
• 金额: $ 20.91万
• 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/7244312
• 关键词: Blood gas; Breathing; Class; Complex; Condition; Conflict (Psychology); Coupling; Data; Dyes; Frequencies; Generations; Grant; Homeostasis; In Vitro; Investigation; Light; Maintenance; Mammals; Mediating; Membrane; Membrane Potentials; Monitor; Neurons; Optics; Pacemakers; Physiological; Play; Population; Preparation; Property; Research; Respiration; Respiratory Burst; Rest; Role; Signal Transduction; Slice; Solutions; Structure; Surface; System; Techniques; Testing; Title; Trees; Work; base; design; insight; interest; neural circuit; optical imaging; postsynaptic; research study; respiratory; response; voltage

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（申请人提供）：新证据表明，两个机械上不同的空间分开网络可以独立产生呼吸节奏。我们建议，这两个网络协同满足维持血液稳态所需的适应性和鲁棒性的矛盾要求。这一新发现强调网络互动在节奏生成中的作用。由于当前可用的准备工作可以轻松访问神经元，但过于降低（横切准备工作），或保留感兴趣的网络，但不允许轻松访问它们（整体准备），我们已经开发了一个倾斜的Saggital切片准备工作，以保留网络，但可以很好地访问感兴趣的网络。我们使用可渗透CA ++指示器的光学记录来确定切片的最佳参数，并使用光学记录技术通常沿着呼吸调制的神经元的神经元延伸在Saggital Slice表面的腹侧髓质中的呼吸调制神经元柱进行监测。我们将使用光学信号来识别2种内源性爆发的呼吸神经元，以使用细胞内记录技术进行详细研究。这些内源性囊泡的不同之处在于，一个人群会随着膜电位的函数（依赖电压的内源性泡沫； vdeb）改变其爆发频率，而另一个人则不（不依赖电压的内源性伯斯特； Vieb）。由于这种差异，VDEB周期周期可以通过短暂的或超极化的脉冲改变。虽然Vieb对此类输入的敏感程度较小。这为我们的假设提供了一种机制。我们建议VDEB介导循环到周期的适应性对呼吸节奏生成网络的适应性，而VIEBS通过快速恢复基线节奏来保持网络稳定性。我们建议通过选择性调节VIEB和VDEB网络以及在单个神经元级别的网络级别测试该假设，通过表征突触隔离的VIEB和VDEB中的扰动响应。