NEURAL MECHANISMS OF CENTRAL CARDIOVASCULAR CONTROL

中枢心血管控制的神经机制

• 批准号: 6183564
• 负责人: JOHN B CABOT
• 金额: $ 31.76万
• 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 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6183564
• 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展

项目成果

Enhancement of heart rate responses during conditioning and sensitization following interruption of raphe-spinal projections.

中缝脊髓投射中断后的调节和敏化过程中心率反应增强。

• DOI: 10.1523/jneurosci.01-07-00760.1981
• 发表时间: 1981
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Cabot,JB;Goff,DM;Cohen,DH
• 通讯作者: Cohen,DH

Effects of spinal lesions on substance P levels in the rat sympathetic preganglionic cell column: evidence for local spinal regulation.

脊柱病变对大鼠交感神经节前细胞柱 P 物质水平的影响：局部脊柱调节的证据。

• DOI: 10.1016/0306-4522(84)90300-2
• 发表时间: 1984
• 期刊: Neuroscience
• 影响因子: 3.3
• 作者: Davis,BM;Krause,JE;McKelvy,JF;Cabot,JB
• 通讯作者: Cabot,JB

Some principles of the spinal organization of the sympathetic preganglionic outflow.

脊柱组织交感神经节前流出的一些原理。

• DOI: 10.1016/s0079-6123(08)61857-9
• 发表时间: 1996
• 期刊: Progress in brain research
• 作者: Cabot,JB

Pincher, a pinocytic chaperone for nerve growth factor/TrkA signaling endosomes.

Pincher，一种用于神经生长因子/TRKA信号内体的皮细胞伴侣。

• DOI: 10.1083/jcb.200201063
• 发表时间: 2002-05-13
• 期刊: JOURNAL OF CELL BIOLOGY
• 影响因子: 7.8
• 作者: Shao, Yufang;Akmentin, Wendy;Toledo-Aral, Juan Jose;Rosenbaum, Julie;Valdez, Gregorio;Cabot, John B;Hilbush, Brian S;Halegoua, Simon
• 通讯作者: Halegoua, Simon

Light microscopic observations on the morphology of sympathetic preganglionic neurons in the pigeon, Columba livia.

鸽子交感神经节前神经元形态的光显微镜观察。

• DOI: 10.1016/0306-4522(87)90105-9
• 发表时间: 1987
• 期刊: Neuroscience
• 影响因子: 3.3
• 作者: Cabot,JB;Bogan,N
• 通讯作者: Bogan,N