FORMATION AND MAINTENANCE OF NEUROMUSCULAR SYNAPSES

神经肌肉突触的形成和维持

• 批准号: 3400821
• 负责人: WESLEY J THOMPSON
• 金额: $ 12.05万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-06-01 至 1995-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3400821
• 关键词: axon; binding proteins; cell differentiation; electrophysiology; gene expression; histochemistry /cytochemistry; immunochemistry; innervation; laboratory mouse; laboratory rat; monoclonal antibody; motor neurons; myofibrils; myogenesis; myosins; neurogenesis; neuromuscular function; neuromuscular junction; neurophysiology; newborn animals; opossums; striated muscles; synapses; synaptogenesis

DESCRIPTION (Investigator's Abstract): An examination of synapse formation and rearrangement ("synapse elimination") occurring in neonatal rat and mouse muscles is proposed. The long-term goal is to understand the mechanisms leading to the formation of specific synaptic connections and determining that all but one of the early synaptic connections are to be lost. The project has five specific aims. (1) To identify a cell-surface antigen present on muscle fibers which is responsible for the generation of fiber-type selective synaptic connections.Monoclonal antibodies will be prepared to membranes of fetal/neonatal muscles and screened for qualitative or quantitative differences in their binding to membranes of different fiber types. These antibodies will be used to examine the expression of candidate molecules during synaptogenesis in fetal and adult muscles. (2) To investigate a molecularcomponent of the neuromuscular junction recognized by monoclonal antibody 3G2. This monoclonal recognizes a previously undescribed, subsarcolemmal component of the junction whose expression requires innervation. This component appears at the junction during the time in early postnataldevelopment when synapse elimination is generating singly innervated fibers. The component recognized by this antibody will be characterized molecularly and its expression in fibers undergoing synapse elimination examined in detail. In addition, experiments will be performed to determine whether the neural control over the expression of the molecule is mediated by nerve-induced muscle activity or by nerve-released trophic factors. (3) To examine the role of differential neural activity and synapse elimination. A portion of the innervation of a muscle will be stimulated in order to examine whether active axons have any competitive advantage over less active axons in the process of synapse elimination. (4) To determine how homogeneity of fiber types within motor units is generated following the conclusion of synapse elimination. Motor units at the conclusion of synapse elimination differ in their size and fiber-type homogeneity from those in the adult, implying further readjustments in muscle innervation. The composition and size of motor units during the period immediately following the end of synapse elimination will be determined in order to investigate thses rearrangements. (5) To describe how fiber types differentiate in the opossum and to determine the role of the nervous system in promoting this differentiation. Opossums are born extremely immature; their hindlimbs are little more than limb buds. The differentiation f fiber types in the opossum hindlimb will be examined using antibodies to myosin heavy chains, and ablation of the lumbar spinal cord willbe performed to investigate the role of innervation in this differentiation and in the generation of secondary muscle fibers.

描述（研究者的摘要）：突触形成的检查 在新生大鼠和 提出了小鼠肌肉。 长期目标是了解 导致特定突触连接形成的机制和 确定除早期的突触连接之一以外的所有内容都是 丢失的。 该项目具有五个特定的目标。 （1）识别细胞表面 肌肉纤维上存在的抗原，这是负责产生的 纤维型选择性突触连接。单克隆抗体将是 准备为胎儿/新生儿肌肉的膜，并筛选 它们与膜的结合中的质量或定量差异 不同的纤维类型。 这些抗体将用于检查 胎儿和成人突触发生过程中候选分子的表达 肌肉。 （2）研究神经肌肉的分子成分 通过单克隆抗体3G2识别的结。 这个单克隆识别 以前未描述的连接处的子囊膜组件 表达需要神经。 该组件出现在交界处 在纳塔尔德阶层早期消除时，消除突触的时间 产生单一神经支配的纤维。 识别的组件 抗体将被表征分子及其在纤维中的表达 详细检查了淘汰突触的消除。另外，实验 将执行以确定对神经的控制是否 分子的表达是由神经诱导的肌肉活性或 通过神经释放的营养因素。 （3）检查差异的作用 神经活动和突触消除。 一部分 将刺激肌肉，以检查活动轴突是否具有 在突触过程中，与较少活跃轴突相比的任何竞争优势 消除。 （4）确定电动机中纤维类型的同质性 在消除突触的结论之后，产生了单位。 发动机 突触消除结束时的单位的大小不同， 成人中的纤维型同质性，这意味着进一步 肌肉神经的重新调整。 电机的组成和大小 突触结束后紧接的期间单位 将确定消除以调查THSE 重排。 （5）描述纤维类型如何区分 负鼠并确定神经系统在促进这一方面的作用 分化。 负鼠天生极不成熟。他们的后肢是 仅仅是肢体芽。 差异化纤维类型 负鼠后肢将使用肌球蛋白重链抗体检查， 腰脊髓的消融将进行调查 神经的作用在这种差异化和产生中 次级肌肉纤维。