NEURAL MECHANISMS OF CENTRAL CARDIOVASCULAR CONTROL

中枢心血管控制的神经机制

• 批准号: 2215714
• 负责人: JOHN B CABOT
• 金额: $ 25.36万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-01 至 1997-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2215714
• 关键词: autoradiography; axon; baroreceptors; blood pressure; cardiovascular function; central nervous system; electron microscopy; histochemistry /cytochemistry; laboratory rat; neural information processing; neural inhibition; neuroanatomy; neurogenic hypertension; neurotransmitters; reflex; spinal cord; spinal nerves; sympathetic ganglion; sympathetic nervous system

Impressive progress has been made in defining and understanding supraspinal pathways with projections to spinal sympathetic preganglionic neurons (SPNs). In contrast, there has been little progress in characterizing another fundamental set of central nervous system pathways involved in the direct regulation of the sympathetic outflow, and therefore in the control of cardiovascular function. Almost nothing is known about putative neurotransmitters released by, or the locations of the cells of origin which give rise to, intraspinal circuits with monosynaptic connections to sympathetic preganglionic neurons. The present application focuses efforts in this direction and is particularly concerned with the identification of inhibitory pathways that are likely to be critical for the normal regulation of cardiovascular function and which may be compromised in at least one example of chronic, sympathetic hyperactivity. Using (1) pre- and postembedding immunoperoxidase, immunofluorescence, and immunogold immunocytochemical procedures; and (2) trans-synaptic and transneuronal labeling methods, the following light and electron microscopic projects have been proposed. Specific Aim 1 would test the hypothesis that glycine is an inhibitory neurotransmitter contained in terminals contacting sympathetic preganglionic neurons. The projects would determine: (1) the intracellular, somadendritic localization of glycine receptor-like immunoreactivity (GlyR-LIR, 93 kd subunit) within retrogradely labeled SPNs in four autonomic nuclei in thoracic spinal cord (Ilp, Ilf, IC, and CA); (2) whether terminal boutons opposite postsynaptic GlyR-LIR exhibit a homogeneous morphology; and (3) if boutons containing gamma-aminobutyric acid-like immunoreactivity (GABA-LIR) are opposite postsynaptic GlyR-LIR within SPNs. Specific Aim 2 would test the hypothesis that spinal' interneurons in laminae V and VII of thoracic spinal cord give rise to principal or collateral axon projections to SPNs. The studies would determine: (1) the segmental and intersegmental (propriospinal) distributions of spinal interneurons projecting to SPNs that have been retrogradely labeled with one of two transneuronally transported tracer substances: wheat germ agglutinin (WGA) or the atoxic binding fragment of tetanus toxin, Fragment C (TTC); and (2) whether the laminar and segmental distributions of WGA- or TTC-labeled spinal interneurons shift or remain constant when populations of SPNs with different postsynaptic targets are retrogradely labeled. Specific Aim 3 would test the hypothesis that transneuronally WGA- or TTC-labeled spinal-SPN pathways originating in laminae V and VII of thoracic spinal cord synthesize and release the inhibitory neurotransmitters glycine or GABA, and/or the excitatory neurotransmitter/ neuromodulator substance P(SP): do WGA- or TTC-labeled interneurons contain GABA-, glycine-, or SP-LIR? Specific Aim 4 would test the hypothesis that cardiovascular hyperactivity manifest in tetanus is a consequence of intoxication of inhibitory synapses contacting SPNs. The experiments would establish whether trans-synaptically TTC-labeled terminal boutons on SPNs in Ilf, Ilp, IC and CA: (1) contain GABA-LIR; and/or (2) are opposite postsynaptic GlyR-LIR. All experiments would be performed in rats.

在定义和理解方面取得了令人印象深刻的进步 脊柱交感神经前的脊柱前途径 神经元（SPN）。 相比之下，几乎没有进展 表征另一组基本的中枢神经系统途径 参与了交感神经流出的直接调节， 因此，在控制心血管功能中。 几乎没有 关于发布的推定神经递质的了解或 产生的原始单元，带有脊柱内回路 单突触连接与交感神经前神经元。 这 目前的应用集中于这个方向，尤其是 与可能是可能的抑制途径有关 对于心血管功能的正常调节至关重要 至少一个慢性，同情的例子可能会妥协 多动症。 使用（1）预拟合的免疫过氧化物酶， 免疫荧光和免疫金免疫细胞化学程序； （2） 反式突触和跨神经元标记方法，以下光 已经提出了电子显微镜项目。 具体目标1 会检验甘氨酸是抑制性神经递质的假设 包含在接触交感神经前神经元的末端中。 这 项目将确定：（1）细胞内，体系 甘氨酸受体样免疫反应性的定位（Glyr-LIR，93 kD 亚基）在四个自主核中逆行标记的SPN中 胸脊髓（ILP，ILF，IC和CA）； （2）终端式胎顿是否 相反的突触后类血液表现出均匀的形态； （3） 如果含有γ-氨基丁酸样免疫反应性的胸部 （gaba-lir）在SPN中与突触后类似叶lile相反。 具体目标 2将检验以下假设：椎板V和 胸脊髓的VII产生主轴突或附带轴突 对SPN的预测。 研究将确定：（1）分段和 脊髓中间神经元的段（骨脊髓）分布 投影给已逆行标记的SPN之一 跨神经运输的示踪物质：小麦胚芽凝集素 （WGA）或破伤风毒素，片段C（TTC）的毒性结合片段； （2）WGA-的层流和分段分布或 当种群时，TTC标记的脊柱中间神经元移动或保持恒定 具有不同突触后靶标的SPN逆行标记。 特定目标3将检验跨性wgA或跨性别的假设 TTC标记的脊柱SPN途径源自层v和VII 胸脊髓合成并释放抑制作用 神经递质甘氨酸或GABA和/或兴奋性 神经递质/神经调节剂P（SP）：wga-或ttc标记 中间神经元包含GABA-，甘氨酸或SP-LIR？具体目标4将 测试心血管多动症中表现在破伤风中的假设 是抑制性突触接触SPN的中毒的结果。 这些实验将确定是否具有反触发性TTC标记 ILF，ILP，IC和CA的SPNS上的末端胸道：（1）包含GABA-LIR； 和/或（2）相反的突触后血液。 所有实验都是 在大鼠中进行。