Lateral Pontine Neurons in the Control of Breathing

描述（由申请人提供）：有大量证据表明，侧脑桥内的神经元在神经发生、控制和调节呼吸中起着重要作用。从出生之日起，其神经元活动的扰动显着改变呼吸。这项建议的基本目标是系统分析的侧桥，一个重要的，但知之甚少的区域参与呼吸控制。我们的初步数据表明，从臂旁复合体向腹侧延伸的脑桥外侧神经元的中等密度走廊，单突触投射到延髓腹外侧的呼吸神经元，即，腹侧呼吸群（VRG），通常被认为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神经元尚不清楚，引起这种连接的脑桥神经元的性质也不清楚。靶向VRG的脑桥神经元的放电模式（紧张性或阶段性呼吸）尚不清楚，向VRG神经元提供突触输入的递质的兴奋性或抑制性也不清楚。虽然VRG投射脑桥区域的连续性质表明它们形成呼吸相关的宏观结构，但其不同节段的不同解剖学连接表明多达5个离散的功能组。将使用各种技术来实现以下具体目标。1)负责控制吸气和呼气持续时间的脑桥外侧神经元在哪里？它们是否表现出阶段性呼吸放电模式？2)哪些解剖学上定义的VRG神经元接受来自每个确定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)单个脑桥神经元到特定VRG神经元的活动模式和单突触连接是否与计算模型预测的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脑桥神经元簇，其改变所识别的VRG神经元的活性和呼吸节律。顺行标记的脑桥轴突的光和电子显微镜（EM）分析将与逆行标记和神经化学标记物（例如，神经激肽-1受体），以区分固有延髓和球脊髓VRG神经元亚群和颅运动神经元。交叉相关分析和尖峰触发的平均值将用于评估侧桥的呼吸细胞和电生理学定义的VRG神经元之间的功能关联。

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.