Lateral Pontine Neurons in the Control of Breathing

脑桥外侧神经元控制呼吸

• 批准号: 6719570
• 负责人: DONALD R. MC CRIMMON
• 金额: $ 36.82万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6719570
• 关键词: aminoacid; electron microscopy; immunocytochemistry; laboratory rat; neurons; neuroregulation; neurotransmitters; pons; pulmonary respiration; respiration regulatory center; respiratory function; synapses

DESCRIPTION (provided by applicant): Evidence is substantial that neurons within the lateral pons play a fundamental role in the neurogenesis, control and modulation of breathing. From the day of birth, perturbation of its neuronal activity significantly alters breathing. The fundamental goal of this proposal is the systematic analysis of the lateral pons, an important but poorly understood region involved in respiratory control. Our preliminary data indicate that a moderately dense corridor of lateral pontine neurons extending ventrally from the parabrachial complex, monosynaptically projects to respiratory neurons within the ventrolateral medulla, i.e., the ventral respiratory group (VRG), generally accepted as a crucial region in the generation of respiratory rhythm and pattern. The specific VRG neurons receiving this input are unclear, as is the nature of the pontine neurons giving rise to this connection. The discharge pattern (tonic or phasic respiratory) of pontine neurons targeting the VRG is not known, nor is the excitatory or inhibitory nature of their transmitters providing synaptic inputs to VRG neurons. Although the contiguous nature of the VRG projecting pontine regions suggests they form a respiratory related macrostructure, distinct anatomical connections for its different segments suggests as many as 5 discrete functional groups. A combination of techniques will be used to address the following Specific Aims. 1) Where are the lateral pontine neurons responsible for controlling inspiratory and expiratory durations and do they exhibit phasic respiratory discharge patterns? 2) Which anatomically defined classes of VRG neurons receive monosynaptic inputs from pontine neurons in each identified region, and what fast amino acid transmitters do they use? 3) Are activity patterns and monosynaptic connections of individual pontine neurons onto specific VRG neurons consistent with their selective role in respiratory rhythm and pattern control as predicted by computational models? Chemical stimulation and inhibition will identify discrete pontine neuron clusters that change the activity of identified VRG neurons and respiratory rhythm. Light and electron micrographic (EM) analysis of anterogradely labeled pontine axons will be combined with retrograde labeling and the presence of neurochemical markers (e.g., neurokinin-1 receptors) to distinguish propriobulbar and bulbospinal VRG neuron subgroups and cranial motoneurons. Cross-correlation analysis and spike-triggered averaging will be used to assess functional associations between respiratory cells of the lateral pons and electrophysiologically defined VRG neurons.

描述(由申请人提供)：大量证据表明，侧脑桥内的神经元在呼吸的神经发生、控制和调节中发挥着重要作用。从出生的那一天起，它的神经元活动的扰动就会显著改变呼吸。这一建议的基本目标是系统地分析侧脑桥，这是一个重要但知之甚少的区域，涉及呼吸控制。我们的初步数据表明，一条中等密度的桥脑外侧神经元走廊从臂旁复合体腹侧延伸到延髓腹外侧区内的呼吸神经元，即腹侧呼吸群(VRG)，通常认为腹侧呼吸群是呼吸节律和模式产生的关键区域。接受这种输入的特定VRG神经元以及引起这种联系的脑桥神经元的性质都不清楚。针对VRG的脑桥神经元的放电模式(强直或时相呼吸)尚不清楚，其向VRG神经元提供突触输入的递质的兴奋性或抑制性也未知。尽管VRG投射脑桥区的毗邻性质表明它们形成了一个与呼吸相关的宏观结构，但其不同节段的不同解剖连接表明多达5个不同的功能群。将使用多种技术来解决以下具体目标。1)桥脑外侧神经元在哪里负责控制吸气和呼气持续时间，它们是否表现出呼吸时相放电模式？2)在解剖学上定义的哪类VRG神经元接受来自每个识别区域的脑桥神经元的单突触输入，它们使用什么快速氨基酸递质？3)单个脑桥神经元的活动模式和与特定VRG神经元的单突触连接是否与计算模型预测的它们在呼吸节律和模式控制中的选择性作用一致？化学刺激和抑制将识别离散的桥脑神经元簇，从而改变已识别的VRG神经元的活动和呼吸节律。对顺行标记的脑桥轴突的光镜和电子显微镜(EM)分析将结合逆行标记和神经化学标记物(如神经激肽-1受体)的存在来区分固有球和球脊髓VRG神经元亚群和脑运动神经元。交叉相关分析和棘波触发平均将被用来评估侧脑桥呼吸细胞和电生理定义的VRG神经元之间的功能联系。