DEVELOPMENT OF RESPIRATORY PATTERN GENERATION

呼吸模式生成的开发

基本信息

批准号：
2225559
负责人：
ALFRED P FISHMAN
金额：
$ 19.86万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
1994
资助国家：
美国
起止时间：
1994-04-01 至 1997-03-31
项目状态：
已结题

项目摘要

Little is currently known about the neural development of the respiratory pattern generator. Development can be viewed in two ways; first, with evolution across species and second with maturation with a single species. Early air-breathing species represent an attractive model in both regards. Although these species use a completely different method to ventilate their lungs (the buccal force pump) the mechanisms controlling respiratory timing intervals are remarkably similar to that in mammals. Thus, the timing module for respiration is likely to already have been developed in these primitive air-breathers. With evolution it is the circuits that shape the final respiratory burst that must have changed, as the mechanical act of breathing moved from the buccal force pump to suctional breathing produced by the diaphragm in mammals. One current view as to the mechanism for respiratory timing in mammals is that it is produced by a neural network, in which post-inspiratory cells plays a critical role. It will be interesting to determine whether a post-inspiratory phase is present also in early breathing species. That this is present is supported by our preliminary studies in the larval form of Rana catesbeiana (tadpole). Studies in these species provide, moreover, a model system in which to study development of the underlying neural mechanisms. Their maturational development is well characterized and there are 25 distinct stages recognized. During development there are distinct alterations in the neural output related to ventilation with increasing complexity in the characteristics of the neural burst for lung ventilation. The post-inspiratory phase seems to arise relatively late in development. Certain of the maturational changes in tadpole in the neural activity related to ventilation parallel the changes described in, the albeit limited, developmental studies in mammals. It is our goal to utilize this development model (tadpole) to study how the pattern generator for respiration arises during maturation. Our focus is initially on studying the characteristics of the changes in neural output with maturation, an essential descriptive step. Thereafter we will study the changes in the role of fast synaptic inhibition, the alterations in the patterns of synaptic input into the relevant motoneurons and changes in the types of promotor cells present. The results we obtain will be interpreted within the framework of the increasing body of knowledge as to neural development in this much studied model. These studies at the level of the development of the neural circuitry are an essential prerequisite to future studies of the changes in intrinsic properties of the relevant neurons and how such changes are programmed at the level of the genome.

目前对呼吸道神经发育知之甚少模式生成器。可以通过两种方式观看发展；首先，与跨物种的进化，其次是成熟的物种。早期的空气呼吸物种代表了一个有吸引力的模型这两个方面。尽管这些物种使用了完全不同的方法为了通风他们的肺（颊力泵）机制控制呼吸时序间隔与此非常相似在哺乳动物中。因此，呼吸的定时模块可能已经在这些原始的气ing中已经开发了。随着进化是塑造最终呼吸爆发的电路改变了，随着呼吸的机械性能从颊力移动泵中膜在哺乳动物中产生的呼吸。一关于哺乳动物呼吸时序机制的当前观点是它是由神经网络产生的，启发性细胞发挥关键作用。确定是否是否早期呼吸物种也存在启动后阶段。那我们在幼虫中的初步研究支持了这一点 Rana Catesbeiana的形式（the）。这些物种提供的研究，此外，一个研究基础开发的模型系统神经机制。他们的成熟发展的特征是并且有25个不同的阶段。在那里开发期间是与通风有关的神经输出的明显改变肺神经爆发特征的复杂性提高通风。启发性阶段似乎相对较晚在开发中。某些the的成熟变化与通风相关的神经活动平行于所描述的变化，尽管有限，哺乳动物的发展研究。这是我们的目标利用此开发模型（t）来研究模式如何成熟期间出现呼吸的发生器。我们的重点是最初研究神经输出变化的特征随着成熟，这是一个必不可少的描述步骤。此后我们将学习快速突触抑制的作用的变化，改变的改变突触输入中相关运动神经元的模式和变化在存在的启动子细胞中。我们获得的结果将是在不断增加的知识体系的框架内解释为在这个众所周知的模型中神经发育。这些研究神经回路的发展水平是必不可少的未来研究对内在特性变化的前提相关神经元以及如何在基因组。