DEVELOPMENT AND REGENERATION OF SENSORY-MOTOR SYNAPSES

随着神经系统的发育，神经元变得特定， 突触连接的精确模式 神经元的一些方面 表型可能由细胞的谱系及其 在发育中的胚胎中。 存在化学信号 提供了另一种机制， 影响细胞的发育命运。 神经活动也可以 形成突触连接的最终模式。 的知识 这三种机制是如何运作的， 神经细胞最初是如何制造，然后再进行提炼和维持 是理解神经细胞最初是如何 建立、完善并保持它们之间的正确联系。 脊髓中的突触连接由初级感觉 支配肌肉和皮肤的传入纤维提供了一个极好的 在单一层面上研究这个问题的系统， 功能鉴定细胞 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没有。 周边目标 感觉神经元的数量是相对 肌肉与皮肤细胞类型的数量。 其主要目的是 建议是确定这种影响是否是由选择性的 预先确定的感觉神经元的存活，或者如果外周 靶点对感觉神经元表型具有指导作用。 青蛙体内的感觉纤维在被切断后可以再生。 在背根中中断。 虽然它们会重新激活 具有高度特异性的运动神经元，它们不会重新 在背柱内建立长纤维束。 一 这项提议的第二个目的是观察促神经突因子 在体外工作也将刺激轴突再生内 脊髓的白色物质。 这些研究可能有助于 在人类脊髓意外损伤后实现再生 损伤 最后，我们建议继续我们的研究机制， 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，介导简单的 牵张反射被其他感觉刺激抑制 传入神经 以前的研究表明， 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 抑制了这条通路中的突触传递 实验中使用 阻断这些受体类型中的每一种的药理学试剂应 使我们能够确定哪种类型的抑制 生理学观察

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.