MOLECULAR EFFECTS OF EARLY EXPERIENCE ON MOTOR NEURON

早期经历对运动神经元的分子影响

• 批准号: 3084079
• 负责人: Robert G Kalb
• 金额: $ 6.64万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3084079
• 关键词: antigen antibody reaction; antigens; brain cell; early experience; electron microscopy; gene expression; hamsters; human tissue; lateral geniculate body; monoclonal antibody; motor neurons; neurogenesis; neuromuscular function; spinal cord; tissue /cell culture; visual feedback

During critical periods in neural development, the structure and function of the CNS can be profoundly influenced by an organism's interactions with its environment. In cats for example, the formation of normal lamination patterns in the dorsal lateral geniculate nucleus (LGN) and of ocular dominance columns in the striate cortex require normal early visual experience. In addition to anatomical and physiological changes, molecular characteristics of neurons are also sensitive to early visual experience. Monoclonal antibody Cat-301 recognizes an antigen on LGN Y-cells whose expression is tied to normal visual experience early in life. Monocular lid suture at birth not only inhibits the physiological and morphological development of Y- cells in the deprived layers of the LGN, but also the expression of the Cat-301 antigen on the same cells. After the critical period, monocular lid suture does not effect Y-cell morphology or physiology and likewise the Cat-301 antigen is unaffected. These findings suggest that the expression of the Cat-301 antigen provides a positive molecular marker for critical period events in visual system development. Our recent work indicates that Cat-301 is expressed on spinal cord motor neurons of hamsters in an experience-dependent manner. Just as Cat-301 expression on Y-cells is tied to normal early visual experience, its expression on hamster motor neurons is tied to normal neuromuscular experience in early life. Manipulating the neuromuscular environment in maturity has no effect on Cat-301 expression, indicating that its expression is not simply activity-dependent. Here we propose studies using the hamster spinal cord system to study experience-dependent features of development. This system presents many advantages for studying the neural activity that contributes to normal development as the motor unit is amenable to pharmacologic dissection, ultrastructural analysis and in vitro manipulation. Pharmacological studies will test the contribution of the components of the motor unit to development using a-bungarotoxin, colchicine and tetrodotoxin. EM studies will correlate ultrastructural events in synaptogenesis with Cat- 301 expression and critical period phenomena. A motor neuron culture system will be developed to confirm and extend this analysis. Finally, since Cat-301 is expressed on human motor neurons, we will attempt to define a developmental critical period for human motor neurons by assaying Cat-301 expression in human autopsy material of various ages. These studies are designed to increase our understanding of experience-dependent development. This knowledge may have important implications for functional recovery after injury in the developing and adult human CNS.

在神经发育的关键时期，结构和 中枢神经系统的功能可以深刻地受到生物体的影响 与其环境的相互作用。 以猫为例， 背侧形成正常层状图案 膝状核 (LGN) 和眼优势柱 纹状皮层需要正常的早期视觉体验。 此外 解剖学和生理学的变化，分子 神经元的特性对早期视觉也很敏感 经验。 单克隆抗体 Cat-301 识别抗原 LGN Y 细胞上的表达与正常视觉有关 早年的经历。 单眼睑缝合不仅在出生时 抑制Y-的生理和形态发育 LGN 被剥夺层的细胞，而且还表达 相同细胞上的 Cat-301 抗原。 关键期过后， 单眼睑缝合不会影响 Y 细胞形态或 生理学以及 Cat-301 抗原同样不受影响。 这些 研究结果表明 Cat-301 抗原的表达 为关键时期事件提供阳性分子标记 视觉系统开发。 我们最近的工作表明 Cat-301 在脊髓上表达 仓鼠的脊髓运动神经元处于经验依赖状态 方式。 正如 Y 细胞上的 Cat-301 表达与正常表达相关 早期视觉体验及其在仓鼠运动神经元上的表达 与早期生活中的正常神经肌肉体验有关。 成熟时操纵神经肌肉环境没有任何作用 对 Cat-301 表达的影响，表明其表达不 简单地依赖于活动。 在这里，我们建议使用仓鼠脊髓系统进行研究 研究发展的经验依赖性特征。 这 系统为研究神经活动提供了许多优势 这有助于正常发育，因为运动单位是 适合药理解剖、超微结构分析 和体外操作。 药理学研究将测试 运动单元的组成部分对发育的贡献 使用α-金环蛇毒素、秋水仙碱和河豚毒素。 电磁学研究 将突触发生中的超微结构事件与 Cat- 301表达和关键期现象。 运动神经元 将开发文化系统来确认和扩展这一点 分析。 最后，由于 Cat-301 表达于人体运动 神经元，我们将尝试定义一个发育关键期 通过检测人体内 Cat-301 的表达来研究人运动神经元 不同年代的尸检材料。 这些研究旨在加深我们对 依赖经验的发展。 这些知识可能有 对损伤后功能恢复具有重要意义 发育中和成人的中枢神经系统。