NEUROPHARMACOLOGY OF THE BARORECEPTOR REFLEX

这项研究的主要目的是识别和 神经通路、神经递质和突触的特征 参与中枢自主神经和心血管的受体 监管。延髓内三个重要的整合“中心” 已经确定了在中枢心血管系统中起主要作用的 控制力。它们是：1)孤束核(NTS)，2)孤束核 延髓尾侧腹外侧核(Cvm)；3)吻侧腹外侧核 延髓(RVm)。这些延髓区域似乎连接在一个神经内。 调节外周交感神经活动的网络 系统。然而，精确的功能和解剖关系 在这些区域以及神经递质和突触之间 负责它们之间信息传递的受体，以及其他 大脑区域还没有得到很好的描述。拟议的研究将 提供生理、药理、生化和 解决这个问题的解剖学证据。第一 具体目标将是评估CVM和RVM在中央 压力感受器反射、心血管和呼吸调节。这些实验 将使用电解损伤和微量注射药物来治疗 延髓：1)确认CVM在中枢压力感受器反射控制中的作用， 2)确定CVM是否在中枢渐变抑制过程中起作用 独立于压力感受器反射，3)识别兴奋性氨基 RVN中负责调节的酸(EAA)受体类型 交感兴奋信息的神经传递，以及4)决定 中枢神经系统通路和突触受体是否介导 心血管反射可以与基础反应区分开来。 由相同的刺激引起的呼吸反射。第二个具体目标 就是在生化水平上检验氨基酸的功能 中枢心血管控制中的神经递质。激活中枢神经 压力感受性反射和交感兴奋通路与体内的结合 将使用RVM和CVM的微透析来测量局部EAA和GABA 释放与刺激一致。此外，有选择地销毁 投射到这些延髓部位的心血管传入通路 结合体外神经化学分析的组织微穿刺法 将使用CVM和RVM来进一步评估EAA和GABA的作用 在延髓压力感受性反射和心血管调节中。第三个具体问题 AIM将检查功能之间的解剖关系 确定了延髓中的“心血管”区域。这些实验是 旨在提供结构基础，以补充功能 从具体目标1和2概述的研究中获得的结果。 对中枢神经系统的组织和神经药理学的知识 心血管控制可能有助于为设计提供合理的基础 对治疗病理异常有用的药物，如 高血压。

The principal aim of this research is the identification and characterization of neural pathways, neurotransmitters and synaptic receptors which participate in central autonomic and cardiovascular regulation. Three important integrative "centers" in the medulla oblongata have been identified which play a major role in central cardiovascular control. These are: 1) the nucleus of the tractus solitarius (NTS), 2) the caudal ventrolateral medulla (CVM), and 3) the rostral ventrolateral medulla (RVM). These medullary regions appear to be linked within a neural network that regulates the activity of the peripheral sympathetic nervous system. However, the precise functional and anatomical relationship between these areas, as well as the neurotransmitters and synaptic receptors responsible for information transmission between them, and other brain regions have not been well characterized. The proposed research will provide convergent lines of physiological, pharmacological, biochemical and anatomical evidence with which to address this question. The first Specific Aim will be to evaluate the role of the CVM and RVM in central baroreflex, cardiovascular and respiratory regulation. These experiments will employ electrolytic lesions and microinjection of drugs int the medulla to: 1) confirm the role of the CVM in central baroreflex control, 2) determine if the CVM plays a role in central sympthoinhibitory processes independently of baroreceptor reflexes, 3) identify the excitatory amino acid (EAA) receptor types in the RVN which are responsible for mediating neural transmission of sympathoexcitatory information, and 4) determine whether the CNS pathways and synaptic receptors which mediate cardiovascular reflexes can be distinguished from those which underlie respiratory reflexes evoked by identical stimuli. The second Specific Aim is to examine at the biochemical level the function of amino acid neurotransmitters in central cardiovascular control. Activation of central baroreflex and sympathoexcitatory pathways combined with in vivo microdialysis of the RVM and CVM will be used to measure local EAA and GABA release coincident with stimulation. In addition, selective destruction of afferent cardiovascular pathways projecting to these medullary sites combined with in vitro neurochemical analyses of tissue micropunches of the CVM and RVM will be employed to further assess the role of EAA's and GABA in medullary baroreflex and cardiovascular regulation. The third Specific Aim will examine the anatomical relationship between functionally identified "cardiovascular" regions in the medulla. These experiments are designed to provide the structural foundation to complement the functional results obtained from the studies outlined under Specific Aims 1 and 2. Knowledge of the organization and neuropharmacology of central cardiovascular control may help to provide a rational basis for the design of drugs useful for treating pathological abnormalities such as hypertension.