DEVELOPMENT AND REGENERATION OF SENSORY/MOTOR SYNAPSES

感觉/运动突触的发育和再生

• 批准号: 2265187
• 负责人: ERIC FRANK
• 金额: $ 20.6万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-04-01 至 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2265187
• 关键词: Anura; GABA receptor; afferent nerve; alternatives to animals in research; axon; chick embryo; dorsal root; electrical potential; electrophysiology; fresh water environment; innervation; motor neurons; nervous system regeneration; neurogenesis; neuromuscular transmission; neuronal guidance; neurophysiology; sensorimotor system; spinal nerves; synapses

As the nervous system develops, neurons become specified to make precise patterns of synaptic connections. Some aspects of neuronal phenotype are likely to be determined by a cell's lineage and its position within the developing embryo. Chemical signals present in a neuron's target tissue provide another mechanisms for influencing a cell's developmental fate. Neural activity can also shape the final pattern of synaptic connections. A knowledge of how these three mechanisms operate is basic to an understanding of how nerve cells originally make and then refine and maintain operate is basic to an understanding of how nerve cells originally make and then refine and maintain their proper connections. Synaptic connections in the spinal cord made by primary sensory afferent fibers innervating muscle and skin provide an excellent system for studying this problem at the level of single, functionally identified cells. Sensory neurons innervating muscle spindles form monosynaptic connections with spinal motoneurons, whereas cutaneous sensory neurons do not. The peripheral targets of sensory neurons are important determinants of the relative numbers of muscle vs. cutaneous cell types. A major aim of this proposal is to determine if this effect is caused by the selective survival of pre-determined sensory neurons, or if peripheral targets have an instructive effect on sensory neuron phenotype. Sensory fibers in the frog can regenerate after they are interrupted in the dorsal root. Although they re-innervate motoneurons with a high degree of specificity, they do not re- establish their long-fiber tracts within the dorsal columns. A second aim of this proposal is to see if neurite-promoting factors that work in vitro will also stimulate axon regeneration within the white matter of the spinal cord. Such studies may help in achieving regeneration in human spinal cord after accidental injury. Finally, we propose to continue our studies of the mechanism of presynaptic inhibition of sensory-motor synapses in the amphibian spinal cord. Synaptic transmission between muscle spindle afferents and motoneurons, the pathways that mediates the simple stretch reflex, is inhibited by stimulation of other sensory afferents. Previous work has shown that a major portion of this inhibition is presynaptic and is mediated by the neural transmitter GABA. However, activation of both GABAA and GABAB receptors inhibits synaptic transmission in this pathway. Experiments using pharmacological agents to block each of these receptor types should enable us to determine which type is responsible for the inhibition observed physiologically.

随着神经系统的发展，神经元变得特定于 精确的突触连接模式。神经元的某些方面 表型可能由一个细胞的谱系和它的 在发育中的胚胎中的位置。存在化学信号 在神经元的靶组织中提供了另一种机制 影响细胞发育的命运。神经活动也可以 塑造突触连接的最终模式。关于…的知识 这三种机制是如何运作的，是理解 神经细胞最初是如何制造、提炼和维持的 操作是理解神经细胞最初是如何 建立，然后完善和保持他们的适当联系。 初级感觉在脊髓内形成的突触联系 支配肌肉和皮肤的传入纤维提供了极好的 在单一的层面上研究这个问题的系统， 按功能标识的单元格。支配肌肉的感觉神经元 纺锤体与脊髓运动神经元形成单突触连接， 而皮肤感觉神经元则不是。外围目标 是相关感觉神经元的重要决定因素 肌肉细胞类型与皮肤细胞类型的比较。这样做的一个主要目的是 建议确定这种影响是否是由选择性 预先确定的感觉神经元存活，或者如果是外周的话 靶点对感觉神经元的表型有指导作用。 青蛙体内的感觉神经纤维可以在 在背根被打断。尽管它们重新支配了 运动神经元具有高度的特异性，它们不会重新- 在背柱内建立它们的长纤维束。一个 这项提议的第二个目的是看看促进神经突起的因素 在体外的工作也将刺激轴突再生 脊髓的白质。这样的研究可能有助于 人脊髓意外损伤后实现再生的研究 受伤。 最后，我们建议继续对其机制进行研究。 两栖动物感觉-运动突触的突触前抑制 脊髓。肌梭间突触传递 传入和运动神经元，这些通路调节简单的 伸展反射，受到其他感官刺激的抑制 传入器。先前的研究表明，这其中的很大一部分 抑制是突触前的，由神经递质介导 GABA。然而，GABAA和GABAB受体的激活 抑制这一通路中的突触传递。使用以下工具进行实验 阻断这些受体类型的药物应该是 使我们能够确定哪种类型的抑制负责 从生理上观察到的。