ROLE OF NEUROCHEMICALS IN RESPIRATORY PATTERN FORMATION

呼吸及其在健康和疾病期间的调节， 基本的生理重要性。 在哺乳动物中， 呼吸运动，并由中枢神经回路控制 位于脑干下部 使用活体脑干 切片制备，位于一部分的神经元的特性 这个神经回路，背侧呼吸组（DRG）， 被描述。 背根节是运动前区重要的整合功能 有节奏的呼吸运动的中心。 的长期目标 这项研究计划是为了了解神经化学物质的作用， 在中央呼吸回路的操作和调节中。 本提案的重点将是扩大以前的工作， 脑干切片通过描述部位和机制 神经化学物质对脑区已识别神经元的作用 DRG。 将研究四种药物。 它们是：促甲状腺激素- 释放激素血清素P物质和谷氨酸 所有 在神经末梢中发现了这些神经化学物质 位于背根神经节，已知会影响节律性呼吸 动作 此外，有充分的证据表明， 这些药物在细胞水平上相互作用， DRG神经元的亚群。 体外脑干切片 成年豚鼠的制备物将用于： 1)定义神经元的类（和子类）， 对每种药物有反应DRG 2)确定DRG内多种药物 动作发生 3)确定每种药物的作用机制 研究 这个项目的基本前提是神经控制 哺乳动物的呼吸将无法完全理解，直到 细胞机制，雕塑的活动模式， 单个呼吸神经元被充分描述。 使用 的体外脑干切片制备，结合 复杂的生物物理技术，如电压钳，提供 这是实现这一目标的一个令人兴奋的机会。

Breathing, and its adjusting during health and disease, is of fundamental physiological importance. In mammals, rhythmic breathing movements and controlled by a central neuronal circuit located within the lower brainstem. Using an in vivo brainstem slice preparation, the properties of neurons located in one part of this neuronal circuit, the dorsal respiratory group (DRG), have been described. The DRG is an important premotor integrating center for rhythmic breathing movements. The long term goal of this research program is to understand the role of neurochemicals in the operation and modulation of the central respiratory circuit. The focus of this proposal will be to extend previous work with brainstem slices by describing the site(s) and mechanism(s) of action of neurochemicals on identified neurons in the region of the DRG. Four drugs will be studied. These are: thyrotropin- releasing hormone, serotonin, substance P, and L-glutamate. All of these neurochemicals have been found within nerve terminals located in the DRG and are known to affect rhythmic breathing movements. In addition, there is ample evidence suggesting that these drugs interact at the cellular level to shape the activity in subgroups of DRG neurons. An in vitro brainstem slice preparation from adult guinea pigs will be used to: 1) define classes (and subclasses) of neurons in the region of the DRG which respond to each drug 2) identify sites within the DRG where multiple drug actions occur 3) determine the mechanism(s) of action for each drug studied The underlying premise of this project is that the neural control of breathing in mammals will not fully be understood until the cellular mechanisms which sculpture the patterns of activity in individual respiratory neurons are adequately described. The use of the in vitro brainstem slice preparation, in combination with sophisticated biophysical techniques such as voltage clamp, offers an exciting opportunity for realizing this goal.