TRANSMISSION ACROSS FIRST SYNAPSE OF THE BAROREFLEX

压力反射是大脑神经调节的重要组成部分 心血管系统，但中枢神经系统的细胞基础 中枢神经系统（CNS）对这些反射的贡献知之甚少。该地区 压力感受器传入神经支配的主要部位在背内侧 孤束核（NTS）的一部分。反射研究和 来自髓质的神经元活动的细胞外记录表明， NTS是传入信息被转换的关键区域 在进入控制心率的其他脑区之前 还有血压许多研究表明，NTS的性质 神经元在高血压期间可能发生改变。拟议的工作将侧重于 在表征突触传递的细胞基础上， 传入-NTS突触。中枢神经系统研究受到难以获得 这些小神经元的物理访问和记录条件， 完整的大脑因此，我们对NTS神经元的了解大多基于 细胞外活动记录提供有限的信息。的in 本文报道了一种大鼠延髓纵切片的体外制备方法 使用细胞内记录来研究内侧NTS神经元， 对传入突触输入的反应。纵向切片提供了 重要的优势，通过保留两个漫长的部分的孤独 微电极放置的通道和关键解剖标志， 提供精确的控制实验条件，如药物 浓度的传入轴突的电刺激将用于 引起突触后反应传入-孤束核突触的几个关键问题 传输将被检查包括：1）频率的机制 突触反应的依赖性抑制和 刺激的间歇或突发模式，2）主要的身份 兴奋性递质及其突触后受体类型，3） 抑制性递质在突触中的潜在作用和特性 调制，和4）初级兴奋性传递的可能变化，或 其在遗传性高血压中的调节。一次候选 神经递质包括谷氨酸，P物质，γ-氨基丁酸， 和去甲肾上腺素双重标记（跨神经节转运 主动脉压力感受性神经辣根过氧化物酶及细胞内染色 注射）将用于鉴定表征的神经元， 接受心血管传入输入的神经元。 免疫细胞化学将识别定位于细胞上的神经递质 体或过程。这些研究将提供重要的新 关于中枢神经系统机制的信息， 反射自主控制的听力和血压在正常和 病理状态，如高血压。

Baroreflexes are an important part of the neural regulation of the cardiovascular system, but the cellular basis of the central nervous system (CNS) contribution to these reflexes is poorly understood. The area of densest innervation by the baroreceptor afferents is in the dorsomedial portion of the nucleus of the tractus solitarius (NTS). Reflex studies and extracellular recordings of neuron activity from the medulla suggest that the NTS is a key area where incoming afferent information is transformed before going on to other brain areas involved in the control of heart rate and blood pressure. A number of studies suggest that the properties of NTS neurons may be altered during hypertension. The proposed work will focus on characterizing the cellular basis of synaptic transmission at the afferent-NTS synapse. CNS studies are hampered by difficulties in gaining physical access to these small neurons and in recording conditions in the intact brain. Thus most of what we know about NTS neurons is based on extracellular activity recordings which provide limited information. An in vitro longitudinal slice preparation of the rat medulla has been developed to study medial NTS neurons using intracellular recordings to measure responses to afferent synaptic input. The longitudinal slice offers important advantages by preserving both lengthy sections of the solitary tract and key anatomical landmarks for microelectrode placement and by providing precise of control experimental conditions such as drug concentrations. Electrical stimulation of afferent axons will be used to evoke postsynaptic responses. Several key issues in afferent-NTS synaptic transmission will be examined including: 1) the mechanism of frequency dependent depression of synaptic responses and the influence of intermittent or burst modes of stimulation, 2) the identity of the primary excitatory transmitter and its postsynaptic receptor type, 3) the potential role and identity of inhibitory transmitters in synaptic modulation, and 4) possible changes in primary excitatory transmission or its modulation in genetic hypertension. Primary candidate neurotransmitters include glutamate, substance P, gamma-aminobutyric acid, and norepinephrine. Dual marking (with transganglionic transport of horseradish peroxidase in aortic baroreceptor nerves and intracellular dye injection) will be used to identify neurons characterized electrophysiologically which received cardiovascular afferent inputs. Immunocytochemistry will identify neurotransmitters localized on cell bodies or processes. These studies should provide important new information concerning the CNS mechanisms involved in a critical step of reflex autonomic control of the hear and blood pressure during normal and pathological states such as hypertension.