FORMATION AND ELIMINATION OF NERVE MUSCLE SYNAPSES

神经肌肉突触的形成和消除

• 批准号: 3395462
• 负责人: JEFFREY L DENBURG
• 金额: $ 11.03万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-04-01 至 1988-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3395462
• 关键词: axon; axon reaction; electrophysiology; histochemistry /cytochemistry; hybridomas; immunochemistry; immunofluorescence technique; innervation; interneurons; membrane activity; monoclonal antibody; motor neurons; muscle; nervous system regeneration; neural transmission; neuroanatomy; neurochemistry; neuromuscular system; nonmammalian vertebrate embryology; synapses; tissue /cell culture

The leg neuromuscular system of the cockroach is one in which the formation of connections between identified motor neurons and muscles may be examined in the adult during axonal regeneration and in the embryo during development. We have demonstrated that during regeneration the coxal depressor muscles are initially randomly innervated by all axotomized neurons. This is similar to what occurs during regeneration in mammals. However, in the cockroach, at later times of regeneration the inappropriate connections are eliminated or the correct ones are maintained until one is left with the original innervation pattern. This is similar to events taking place during embryonic development in mammals. Using anatomical and electrophysiological techniques and surgical manipulations we propose to determine the cellular mechanisms involved in the selective elimination of inappropriate connections. Using various biochemical approaches, including hybridoma technology, we propose to identify, isolate, characterize and demonstrate a function for those macromolecules responsible for generating the specificity of these cellular interactions. In addition, using immunohistochemical techniques, attemps will be made to determine whether the same macromolecules and cellular interactions are involved in the initial formation of the innervation pattern of the muscles during embryonic development. The knowledge acquired in this investigation will help us to attain a better understanding of the more general biological phenomena of intercellular recognition and cell growth. Metastasis of tumors, infection of cells by viruses, bacteria and parasites all involve a specific recognition process. Knowledge of the role of cell surface macromolecules in these processes will lead to better therapeutic treatments. The information acquired on the mechanism of the successful regeneration of cockroach motor neuron may also be applicable to attempts to increase the probability of obtaining successful functional regeneration of neurons after injury in humans. Such knowledge would be helpful for the treatment of paraplegics and for other neurological disorders involving neuronal injury like strokes, multiple sclerosis or head injury.

蟑螂的腿部神经肌肉系统 可以检查所识别的运动神经元和肌肉之间的连接 在成年人的轴突再生过程中， 发展 我们已经证明，在再生过程中， 降压肌最初随机受所有轴突切断的神经支配， 神经元 这与哺乳动物再生过程中发生的情况相似。 然而，在蟑螂，在以后的时间再生的不适当的 连接被消除或保持正确的连接，直到一个连接被 留下了原始的神经支配模式 这与事件类似 发生在哺乳动物胚胎发育期间。 使用解剖学和 电生理技术和外科手术，我们建议， 确定参与选择性消除的细胞机制 不适当的连接。 使用各种生物化学方法，包括 杂交瘤技术，我们建议鉴定，分离，表征和 证明了那些大分子的功能 这些细胞相互作用的特异性。 此外，使用 免疫组织化学技术，将进行免疫组化，以确定是否 相同的大分子和细胞相互作用参与了 肌肉的神经支配模式的初始形成， 胚胎发育 在这次调查中获得的知识将 帮助我们更好地理解更普遍的生物学 细胞间识别和细胞生长的现象。 转移 肿瘤、病毒、细菌和寄生虫对细胞的感染， 具体识别过程。 了解细胞表面的作用 这些过程中的大分子将导致更好的治疗 治疗。 获得的关于成功的机制的信息 蟑螂运动神经元的再生也可能适用于尝试 以增加获得成功的功能再生的可能性 神经元损伤后的变化。 这些知识将有助于 治疗截瘫和其他神经系统疾病， 神经元损伤，如中风、多发性硬化症或头部损伤。