ROLE OF NEUROCHEMICALS IN RESPIRATORY PATTERN FORMATION

呼吸及其在健康和疾病期间的调整， 基本的生理重要性。 现在有广泛的 知识体系，主要来自原位脑电生理学 实验，关于中央神经元的组织 启动和协调有节奏呼吸的回路 哺乳动物的运动 我研究的长期目标也是 将这些知识扩展到细胞水平，并定义 中央呼吸回路由一组 解剖学、生物物理学和神经化学构建块。 目前，我的实验室是由一个五年的NIH赠款（HL- 39929-01）。 利用体外脑干切片制备， 该项目旨在确定具体的 神经化学和内在的膜特性在雕刻 位于呼吸组的神经元活动 (DRG)豚鼠。 具体目标是：（一）界定 DRG区域神经元的玻璃（和亚类） 具有独特的形态学、生物物理学和 药理学性质，（ii）确定 这些神经化学物质的作用，和（iii）确定网站内 背根神经节可能发生多种神经化学作用。 建筑 在这种体外方法成功之后，我制定了一个 职业发展计划旨在提高我的解决方案 目前的研究计划，并将其扩展到其他元素的 中央呼吸系统 的中心主题 该开发计划旨在获得全细胞/贴片方面的专业知识 钳夹和神经解剖学染色技术。 为此，A 结合实验室的培训经验， 利用这些技术，与成员持续互动， 肯塔基州大学呼吸组的研究人员， 下一年的研究和研究相关活动的承诺 建议五年。 为了实现这些目标，大学 为我提供了额外的设备和空间 最终实现这些技术在我自己的 实验室 如果这个提议的基本前提是， 作为调查员实现完全独立， 研究生和博士后学生，我必须牢固地建立我的 实验室作为“最先进”生物物理研究的场所 与解剖学定位相结合， 呼吸神经元和神经递质。 的资源和 肯塔基州大学提供的环境，加上 本申请中概述的职业发展计划，确保 这一目标的实现。

Breathing, and its adjustment during health and disease, is of fundamental physiological importance. There is now an extensive body of knowledge, largely derived from in situ leurophysiological experiments, concerning the organization of the central neuronal circuit which initiates and coordinates rhythmic breathing movements in mammals. The long-term goal of my research is too extend this knowledge to the cellular level, and define how the central respiratory circuit is assembled from a collection of anatomical, biophysical, and neurochemical building blocks. Currently, my laboratory is funded by a five year NIH grant (HL- 39929-01). Utilizing an in vitro brainstem slice preparation,, this project is directed towards defining the role of specific neurochemical and intrinsic membrane properties in sculpturing the activity of neurons located within the porsal respiratory group (DRG) of guinea pigs. The specific aims are to: (i) define glasses (and subclasses) of neurons in the region of the DRG possessing unique combinations of morphological, biophysical, and pharmacological properties, (ii) determine the mechanism(s) of action for these neurochemical, and (iii) identify sites within the DRG where multiple neurochemical actions might occur. Building upon the success of this in vitro approach, I have formulated a career development plan designed to enhance the resolution of my current research program and extend it to other elements of the central respiratory circuit in the future. The central theme of this development plan is to acquire expertise in whole cell/patch clamping and neuroanatomical staining techniques. To do this, a combination of training experience in laboratories successfully employing these technologies, continued interaction with members of the Respiratory Group at the University of Kentucky, and a total commitment to research and research related activities for the next five years is proposed. In support of these goals, the University of Kentucky has provided me with the additional equipment and space necessary to eventually implement these techniques in my own laboratory. The underlying premise, if this proposal is that to achieve full independence as an investigator, and attract quality graduate and post doctoral students, I must firmly establish my laboratory as a site where "state of the art" biophysical studies are done in association with the anatomical localization of respiratory neurons and neurotransmitters. The resources and environment available at the University of Kentucky, coupled with the career development plan outlined in this application, assures the realization of this goal.