TRANSMISSION ACROSS FIRST SYNAPSE OF THE BAROREFLEX

压力反射第一个突触的传输

• 批准号: 3358623
• 负责人: Michael Christian Andresen
• 金额: $ 20.68万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-02-01 至 1996-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3358623
• 关键词: afferent nerve; autonomic reflex; baroreceptors; blood pressure; electrophysiology; electrostimulus; heart rate; immunocytochemistry; laboratory rat; microelectrodes; neural transmission; neurogenic hypertension; neurotransmitters; solitary tract nucleus; synapses

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.

压力反射是神经调节的重要组成部分 心血管系统，但中枢神经的细胞基础 系统（CNS）对这些反射的贡献知之甚少。该区域 压力感受器传入的密度神经支配是在背部的 索他座核（NTS）核的一部分。反射研究和 延髓的神经元活性的细胞外记录表明 NTS是转换传入的传入信息的关键领域 在进入控制心率的其他大脑区域之前 和血压。许多研究表明NTS的特性 高血压期间神经元可能会改变。拟议的工作将集中 在表征突触传播的细胞基础时 传入-NTS突触。中枢神经系统研究受到了获得的困难 物理访问这些小神经元和记录条件 完整的大脑。因此，我们对NTS神经元的了解大多数是基于 提供有限信息的细胞外活动记录。一个 已经开发了大鼠髓质的体外纵向切片制剂 使用细胞内记录来研究内侧NTS神经元以测量 对传入突触输入的响应。纵向切片提供 通过保留孤独的两个冗长部分，具有重要的优势 用于微电极放置的区域和钥匙解剖标记以及 提供控制实验条件（例如药物）的精确 浓度。传入轴突的电刺激将用于 引起突触后反应。传入-NTS突触中的几个关键问题 将检查传输包括：1）频率机理 突触反应的依赖抑郁症和 间歇性或爆发模式的刺激模式，2）主要的身份 兴奋性发射器及其突触后受体类型，3） 突触中抑制性发射器的潜在作用和身份 调制和4）主要兴奋性传播或 它在遗传高血压中的调节。主要候选人 神经递质包括谷氨酸，物质P，γ-氨基丁酸， 和去甲肾上腺素。双重标记（带有透射转运 主动脉压力受体神经和细胞内染料中的辣根过氧化物酶 注射）将用于识别表征的神经元 从电生理上接受心血管传入输入。 免疫细胞化学将识别位于细胞上的神经递质 身体或过程。这些研究应该提供重要的新 有关中枢神经系统机制涉及的关键步骤的信息 反射自主控制在正常情况下对听觉和血压的自主控制和 病理状态，例如高血压。