ROLE OF NEUROCHEMICALS IN RESPIRATORY PATTERN FORMATION

呼吸及其在健康和疾病期间的调节，是 基本的生理重要性。现在有一个广泛的 知识体系，主要来自于现场神经生理学 关于中枢神经元组织的实验 启动和协调有节奏的呼吸的回路 哺乳动物的运动。我研究的长期目标也是 将这一知识扩展到细胞级别，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积木。 目前，我的实验室是由美国国立卫生研究院(NIH)的五年拨款(HL- 39929-01年度)。利用体外脑干切片制备， 本项目旨在定义特定的角色 神经化学和内在膜的性质在雕刻 肺呼吸群内神经元的活动 (DRG)豚鼠。具体目标是：(1)界定 背根神经节区域神经元的玻璃体(及其亚类) 具有独特的形态、生物物理和 药理性质，(Ii)确定其作用机制(S) 对这些神经化学物质的作用，以及(Iii)确定 可能发生多种神经化学反应的背根节。建房 在这种体外方法取得成功后，我制定了一种 职业发展计划旨在提高我的决心 目前的研究计划，并将其扩展到 未来的中枢呼吸回路。的中心主题 这一发展计划是为了获得整个单元/贴片的专业知识 夹闭和神经解剖染色技术。要做到这一点，一个 成功结合实验室实训经验 使用这些技术，与成员持续互动 肯塔基大学呼吸小组的成员，总共 致力于下一步的研究和研究相关活动 五年是提议的。为了支持这些目标，大学 为我提供了额外的设备和空间 最终在我自己的系统中实现这些技术所必需的 实验室。基本的前提是，如果这项提议是 作为一名调查员实现完全独立，并吸引质量 研究生和博士后，我必须牢固树立我的 实验室作为“最先进的”生物物理研究场所 是在解剖定位的基础上进行的 呼吸神经元和神经递质。这些资源和 肯塔基大学提供的环境，加上 此申请表中概述的职业发展计划可确保 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.