AFFERENT ORGANIZATION IN NEUROLOGICALS

神经学中的传入组织

• 批准号: 3404041
• 负责人: LEONARD M EISENMAN
• 金额: $ 16.15万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-02-01 至 1995-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3404041
• 关键词: afferent nerve; cerebellar Purkinje cell; dendrites; developmental neurobiology; immunochemistry; immunocytochemistry; laboratory mouse; laboratory rabbit; light microscopy; monoclonal antibody; mutant; neuroanatomy; neurochemistry; olivocochlear bundle; silver impregnation; spinal cord; synapses; synaptogenesis; western blottings

The analysis of afferent organization in neurological mutants has illuminated interesting and potentially revealing model systems which, with further exploration, will undoubtedly provide us with an understanding of important mechanisms in the development of afferent-target relationships. In analyzing the developmental process of afferent organization and afferent-target relationships in the olivocerebellar system of the lurcher mutant mouse, we have demonstrated a specific defect in the transposition of the olivocerebellar fiber from somal synaptic contacts to dendritic synapses. This defect is both afferent specific, since parallel fiber synapses form normal contacts, and membrane specific, as normal synaptic contacts are formed by olivocerebellar fibers onto the Purkinje cell soma, but not its dendrite. Another mutant, the staggerer, exhibits a somewhat complementary defect to lurcher, in that the other major synaptic input to the Purkinje cell, namely the parallel fiber, does not develop. Thus in lurcher and staggerer there are specific, but different, alterations of the two major afferents to the Purkinje cell. Another mutant, meander tail, is characterized by a cerebellum which is partially normal cytoarcbitectually and partly abnormal. It therefore provides an unusual opportunity to analyze normal an abnormal processes of afferent organization and afferent-target relationship in the same animal; an internal control, if you will. This proposal contains experiments to further analyze afferent systems in these mutants. These new experiments are designed to: 1) determine in the lurcher the molecular basis of the specific defect in the synaptogenesis of olivocerebellar fibers and their Purkinje cell target, 2) determine if there is a relationship between the temporal vulnerability of Purkinje cells in the lurcher and their biochemical or positional heterogeneities, 3) determine the molecular basis of the synaptogeneic defect between parallel fibers and Purkinje cells in the staggerer, and 4) examine the organization and synaptic relationship of the spino and olivocerebellar systems in the meander tail mutant mouse to determine the afferent target characteristics which are under target control. The considered use of neurological mutants will enable us to address basic questions concerning the organization and development of afferent systems.

神经学突变体的传入组织分析 具有启发性的有趣且可能揭示的模型系统 进一步的探索，无疑将为我们提供对 传入-靶关系发展中的重要机制。 在分析传入组织的发展过程中， 潜行者橄榄小脑系统中的传入-靶关系 突变的小鼠，我们已经证明了转座中的一个特定缺陷 从胞体突触接触到树突的橄榄小脑纤维 突触。这一缺陷既是传入特有的，因为平行纤维 突触形成正常的接触，与正常的突触一样，是膜特有的 接触是由橄榄小脑纤维在浦肯野细胞体上形成的， 但不是它的树枝状晶体。另一个突变体，交错人，表现出某种程度的 与Lurcher的互补缺陷，因为另一个主要的突触输入到 浦肯野细胞，即平行纤维，不发育。因此，在 摇摇晃晃的和令人震惊的是，有具体的，但不同的，改变 浦肯野细胞的两个主要传入细胞。另一种突变体，曲折尾巴，是 小脑的特点是小脑的细胞学部分正常 而且有一部分不正常。因此，它提供了一个不同寻常的机会 分析传入组织的正常和异常过程 同一动物中的传入-靶关系；内部控制，如果 你会的。 这项建议包含进一步分析传入系统的实验 这些变种人。这些新的实验旨在：1)在 突触发生中特异性缺陷的分子基础 橄榄小脑纤维及其浦肯野细胞靶点，2)决定 浦肯野的时间脆弱性与 潜行者中的细胞及其生化或位置异质性， 3)确定突触发生缺陷的分子基础 交错中的平行纤维和浦肯野细胞，以及4)检查 棘突和橄榄小脑的组织和突触关系 系统在曲折尾巴突变小鼠中确定传入靶标 处于目标控制之下的特征。经过深思熟虑的使用 神经学突变将使我们能够解决以下基本问题 传入系统的组织和发展。