Mechanisms of Activity-Dependent Synaptic Plasticity

描述 (申请人摘要)拟议调查的长期目标 就是了解高血压产生高血压的机制 自主神经突触传递的生理学变化。许多研究 提示高血压人和高血压动物模型表现出 周围交感神经系统活动(SNA)增加。了解以下内容 导致SNA升高的事件及其在发生和发展中的意义 维持血压升高是最基本的。人们一直认为 SNA的增加可能主要源于中枢神经系统。 这得到了某些中枢作用药物的疗效的支持，影响 下丘脑和脑干受累区域的损害 心血管和电解质动态平衡以及多种中枢因素的影响 在交感神经流出时使用荷尔蒙。相比之下，主要的 高血压患者的周围神经系统功能异常 都没有得到很好的记录。一般的方法是监控活动- 颈上神经节神经可塑性的依赖性改变 和分离自高血压大鼠的星状神经节(SG)。我们的假设是 1)高血压引起交感神经突触效应的调节 和2)血管紧张素II(AngII)，无论是通过长期作用于 神经节或通过交感神经系统(SNS)的激活增加 从中枢神经系统(CBS)流出，导致改变 在神经节功能方面。在高血压动物模型中，戏剧性变化 在交感神经节的电生理行为中可以观察到 从动作电位活动模式的改变到神经元的变化 记录在节后神经元中以增强突触的疗效 变速箱。我们的初步数据显示，两种形式的突触 可塑性，即强直后(PTP)和长时程增强(LTP) 在高血压状态下，SCG会受到很大影响。本提案使用 电生理技术、受体放射自显影技术和 神经递质药理学与高血压遗传毒株的协同作用 动物学习高血压的发生和维持如何改变 周围神经元件在自主神经节中的作用。

DESCRIPTION (Applicant's abstract) The long-term objective of the proposed investigation is to understand the mechanisms by which high blood pressure produces profound changes in the physiology of autonomic synaptic transmission. Many studies suggest that hypertensive humans and animal models of hypertension exhibit increased peripheral sympathetic nervous system activity (SNA). Knowledge of the events that lead to elevated SNA and its significance in the genesis and maintenance of elevated blood pressure is rudimentary. It has been thought that increased SNA may originate primarily from the central nervous system. This supported by the efficacy of certain centrally acting drugs, the impact of lesions in regions of the hypothalamus and brainstem involved in cardiovascular and electrolyte homeostasis and the effects of many centrally administered hormones on sympathetic outflow. In contrast, primary abnormalities in the function of the peripheral nervous system in hypertension are less well documented. The general approach is to monitor the activity- dependent changes in neuroplasticity of the superior cervical ganglia (SCG) and stellate ganglia (SG) isolated from hypertensive rat. Our hypotheses are that 1) hypertension induces modulation of synaptic efficacy in sympathetic ganglia, and 2) Angiotensin II (AngII), either by long term actions at the ganglion or by increased activation of sympathetic nervous system (SNS) outflow from the central nervous system (CBS), contributes to the alterations in ganglionic function. In animal models of hypertension, dramatic changes can be observed in the electrophysiological behavior of sympathetic ganglion neurons ranging from alterations in the pattern of action potential activity recorded in postganglionic neurons to an enhanced efficacy of synaptic transmission. Our preliminary data reveal that two forms of synaptic plasticity, namely, post-tetanic (PTP) and long-term potentiation (LTP) in the SCG are profoundly affected during hypertensive states. This proposal uses electrophysiological techniques, receptor autoradiography techniques and neurotransmitter pharmacology in concert with genetic strains of hypertensive animals to learn how genesis and maintenance of high blood pressure alter the function of peripheral neural elements in autonomic ganglia.