Network mechanisms for respiratory rhythm generation

呼吸节律产生的网络机制

• 批准号: 7435192
• 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 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7435192
• 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(由申请人提供)：新的证据表明，两个机械上不同的、空间上分离的网络可以独立地产生呼吸节律。我们认为，这两个网络协调一致地满足了维持血气平衡所需的适应性和稳健性的相互冲突的要求。这一新发现强调了网络互动在节奏生成中的作用。由于目前可用的制备方法可以容易地接触到神经元，但太少(横向切片制备)，或者保留了感兴趣的网络但不允许容易接触到它们(整体制备)，我们开发了倾斜的矢状面制备方法，它保留了目前的整体网络，但提供了良好的接触感兴趣网络的途径。我们使用膜可渗透钙指示剂的光学记录来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片表面的延髓腹外侧部呼吸调制神经元柱的局部网络活动。我们将使用光信号来识别两类内源性呼吸神经元，以便使用细胞内记录技术进行详细研究。这些内源性猝发的不同之处在于，一个种群将其爆发频率作为膜电位的函数来改变(电压依赖型内源性猝发；VDEB)，而另一个种群则不改变(电压非依赖性内源性猝发；VIEB)。由于这种差异，VDEB周期可以通过瞬时去极化或超极化脉冲来改变；而VIEB对这种输入不那么敏感。这为我们的假设提供了一种机制；我们认为VDEB调节呼吸节律产生网络的周期间适应性，而VIEB通过快速恢复基线节律来维持网络的稳定性。我们建议在网络水平上，通过选择性地调制VIEB和VDEB网络，并在单个神经元水平上，通过表征突触分离的VIEB和VDEB的扰动反应来检验这一假说。

项目成果

Semi-automated region of interest generation for the analysis of optically recorded neuronal activity.

• DOI: 10.1016/j.neuroimage.2009.04.016
• 发表时间: 2009-10-01
• 期刊: NeuroImage
• 影响因子: 5.7
• 作者: Mellen NM;Tuong CM
• 通讯作者: Tuong CM

Degeneracy as a substrate for respiratory regulation.

• DOI: 10.1016/j.resp.2010.04.013
• 发表时间: 2010-06-30
• 期刊: RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY
• 影响因子: 2.3
• 作者: Mellen, Nicholas M.

Functional anatomical evidence for respiratory rhythmogenic function of endogenous bursters in rat medulla.

大鼠髓质内源性爆发的呼吸节律发生功能的功能解剖学证据。

• DOI: 10.1523/jneurosci.5510-09.2010
• 发表时间: 2010
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Mellen,NicholasM;Mishra,Deepak
• 通讯作者: Mishra,Deepak