FORMATION AND ELIMINATION OF NERVE-MUSCLE SYNAPSES

神经肌肉突触的形成和消除

• 批准号: 3395468
• 负责人: JEFFREY L DENBURG
• 金额: $ 16.69万
• 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 1991-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3395468
• 关键词: axon; axon reaction; cell cell interaction; cockroach; electrophysiology; glycoproteins; histochemistry /cytochemistry; hybridomas; immunochemistry; immunofluorescence technique; innervation; interneurons; membrane activity; monoclonal antibody; motor neurons; muscle; nervous system regeneration; neural transmission; neuroanatomy; neurochemistry; neurogenesis; neuromuscular junction; neuromuscular system; nonmammalian vertebrate embryology; synapses; tissue /cell culture

The formation of patterned connections between motor neurons and muscles during development in the vertebrates requires specific cell-cell recognition as well as an editing mechanism of synaptic elimination. The complex anatomy of even this relatively simple system is such that an understanding of these phenomena at the cellular and molecular levels is difficult. The leg neuromuscular system of the cockroach is even simpler with muscles innervated by one or a small number of motor neurons. When the axons of these motor neurons are cut, they regenerate and eventually reform synapses with just the original target muscles. However, at early stages of regeneration inappropriate synapses form. The apparent specificity arises from the selective elimination of these mistakes. The cockroach serves as a model system in which to examine common developmental processes at the cellular and molecular levels. The ability to distinguish among target muscles indicates that there are molecular differences between individual motor neurons and between individual muscles. Monoclonal antibodies are available that bind to the surfaces of axon terminals of identified motor neurons. These will be used to purify the antigens and to demonstrate a function for them during regeneration. Tissue culture and immunohistochemical techniques will be used to test the hypothesis that the specificity of the interaction between motor neurons and muscles arises from a selective enhancement of growth and sprouting of axons only in their appropriate target muscles. Recombinant DNA techniques will be used to characterize the candidate recognition macromolecules. The information acquired on the mechanism of the successful regeneration of cockroach motor neurons will also be applicable to attempts to increase the probability of obtaining such regeneration in humans. Such knowledge would be helpful for the treatment of paraplegia, neuromuscular disorders, multiple sclerosis and other neurological disorders involving injury such as strokes and head injury.

运动神经元之间模式连接的形成， 在脊椎动物的发育过程中，肌肉需要特定的 细胞-细胞识别以及突触的编辑机制 淘汰 即使是这个相对简单的 系统是这样的，了解这些现象在 细胞和分子水平是困难的。 腿部神经肌肉 蟑螂的系统甚至更简单，肌肉受 一个或少量的运动神经元。 当这些轴突 运动神经元被切断，它们再生并最终改革 只与原来的目标肌肉形成突触 然而，在早期 再生阶段不适当的突触形成。 表观 特异性产生于选择性消除这些 错误 蟑螂作为一个模型系统， 研究细胞和 分子水平。 区分目标肌肉的能力表明， 运动神经元之间存在分子差异 和肌肉之间的联系。 单克隆抗体是 可利用的结合到轴突终末表面的识别 运动神经元 这些将用于纯化抗原， 在再生过程中发挥作用。 组织 将使用培养和免疫组织化学技术来检测 假设运动之间相互作用的特异性 神经元和肌肉的生长是有选择性的 轴突只在相应的目标肌肉中发芽。 重组DNA技术将用于表征 候选识别大分子。 获得的关于成功的机制的信息 蟑螂运动神经元的再生也适用于 试图增加获得这种再生的可能性 在人类身上。 这些知识将有助于治疗 截瘫、神经肌肉疾病、多发性硬化症和其他 涉及中风和头部等损伤的神经系统疾病 损伤