NEURAL CONTROL OF RESPIRATION

长期目标是分析神经机制， 脊椎动物呼吸，作为实验模型，使用隔离的 新生大鼠的脑干/脊髓。 这种新型制剂 具有显著的实验优势， 细胞内记录的条件，不受限制地访问 脑干，消除来自外围的反馈机制， 对沐浴药物的迅速反应，以及自动持续的 由中枢模式发生器产生的呼吸节律。 该提案的目的是首先验证实验 通过对体外呼吸节律的分析， 对新生大鼠呼吸肌在体活动的影响。 接下来，髓质中关键呼吸神经元的位置将 利用神经递质的喷射来重新设定节律 定时，参考众所周知的呼吸核， 其他哺乳动物 拟议研究中最密集的部分 将在细胞内记录呼吸神经元的定义， 作为产生脉冲爆发或显示突触活动的细胞 与酚类物质的释放相协调。 目前没有 发表的呼吸神经元的细胞内记录， 大鼠制备。 细胞将通过细胞内标记进行常规标记。 注射荧光染料。 研究将侧重于 运动神经元、球脊髓神经元和新的呼吸神经元群。 神经元 它们的位置，活动模式，形态，突触 输入、投影和某些细胞特性将被 表征了 将对以下方面进行更详细的研究： 大鼠膈神经元的多巴胺能神经支配 延髓中缝核 体外大鼠制备， 与浴结合-应用特定的药理学 试剂，将允许在理解基因座方面取得重大进展， 细胞机制和受体类型，介导强大的 呼吸的神经调节。

The long-term goal is to analyze the neural mechanisms of vertebrate respiration, using as an experimental model the isolated brainstem/spinal cord of newborn rats. This novel preparation presents significant experimental advantages such as motionless conditions for intracellular recording, unrestricted access to the brainstem, elimination of feedback mechanisms from the periphery, prompt responses to bath-applied drugs, and an automatic on-going respiratory rhythm produced by a central pattern generator. The aims of this proposal are first to validate the experimental model by analyzing the in vitro respiratory rhythm and comparing it to the in vivo activity of respiratory muscles in newborn rats. Next, the locations of key respiratory neurons in the medulla will be mapped using ejection of neurotransmitters to reset the rhythm timing, with reference to the well-known respiratory nuclei of other mammals. The most intensive part of the proposed research will be to record intracellularly from respiratory neurons defined as cells that produce impulse bursts or show synaptic activity coordinated with the phenic discharge. At present there are no published intracellular recordings from respiratory neurons in this rat preparation. Cells will be routinely marked by intracellular injection of a fluorescent dye. Research will focus on motorneurons, bulbospinal neurons, and novel groups of respiratory neurons. Their locations, activity patterns, morphology, synaptic inputs, projections, and certain cellular properties will be characterized. A more detailed study will be made of the serotonergic innervation of phrenic motorneurons from neurons in the medullary raphe nuclei. The in vitro rat preparation, in conjunction with the bath-application of specific pharmacological agents, will allow significant advances in understanding the loci, cellular mechanisms, and receptor types that mediate the powerful serotonergic modulation of respiration.