Mechanisms of Activity-Dependent Synaptic Plasticity

描述 （申请人摘要）拟议调查的长期目标 是为了了解高血压产生深刻影响的机制 自主神经突触传递的生理变化。 许多研究 提示高血压人类和高血压动物模型表现出 增加周围交感神经系统活动（SNA）。 知识 导致SNA升高的事件及其在起源和 维持高血压是基本的。 人们一直认为 SNA增加可能主要来自中枢神经系统。 这得到了某些中枢作用药物的疗效的支持， 下丘脑和脑干区域的病变， 心血管和电解质稳态以及许多中枢神经系统的影响 对交感神经流出进行激素治疗 相比之下，主要 高血压周围神经系统功能异常 却没有得到很好的记录 一般的做法是监测活动- 上级颈神经节（SCG）神经可塑性的依赖性变化 和星状神经节（SG）。 我们的假设是 1）高血压诱导交感神经系统中突触功效的调节， 神经节，和2）血管紧张素II（AngII），无论是通过长期的行动，在 神经节或交感神经系统（SNS）激活增加 从中枢神经系统（CBS）流出，有助于改变 神经节功能 在高血压动物模型中， 在交感神经节的电生理行为中可以观察到 神经元的范围从动作电位活动模式的改变 记录在节后神经元的突触增强的功效， 传输 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 SCG在高血压状态下受到深刻影响。 该提案使用 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株 动物来了解高血压的发生和维持如何改变 自主神经节中周围神经元的功能。

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.