TRANSMISSION ACROSS FIRST SYNAPSE OF THE BAROREFLEX

压力反射是中枢神经系统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 系统(CNS)对这些反射的贡献还知之甚少。这一地区 压力感受器传入的最密集的神经支配在背内侧 孤束核的一部分。反射研究和 延髓神经元活动的细胞外记录表明 NTS是传入传入信息被转换的关键区域 在继续研究与心率控制有关的其他大脑区域之前 还有血压。多项研究表明，NTS的特性 在高血压期间，神经元可能会发生改变。拟议的工作将集中于 关于表征突触传递的细胞学基础 传入-NTS突触。中枢神经系统的研究因难以获得 物理接触到这些小神经元，并在记录条件下 完整的大脑。因此，我们所知道的关于NTS神经元的大部分是基于 细胞外活动记录提供的信息有限。An In 建立了大鼠延髓的体外纵向切片制备方法 用细胞内记录测量研究NTS内侧神经元 对传入突触输入的反应。纵向切片提供 通过保留孤立面的两个较长部分的重要优势 用于微电极放置的束和关键解剖标志 提供精确的控制实验条件，如药物 浓度。电刺激传入轴突将用于 唤起突触后反应。传入-NTS突触的几个关键问题 传输将包括：1)频率的机制 突触反应的依赖性抑制及三七总皂苷的影响 间歇性或突发性刺激模式，2)初级刺激的同一性 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，以及4)初级兴奋性传递的可能变化或 它在遗传性高血压中的调节作用。初选候选人 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(具有跨神经节转移的 主动脉压力感受器神经中的辣根过氧化物酶和细胞内染料 注射)将用于识别被表征的神经元 接受心血管传入信息的电生理学。 免疫细胞化学将识别定位在细胞上的神经递质 实体或过程。这些研究应该提供重要的新的 关于中枢神经系统机制的信息，涉及 反射自主控制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.