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: 3084080
• 负责人: Robert G Kalb
• 金额: $ 6.89万
• 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/3084080
• 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， 中枢神经系统的功能可以受到生物体的 与环境的相互作用。 以猫为例， 背外侧形成正常的纹层图案 膝状体核（LGN）和眼优势柱 纹状皮质需要正常早期视觉体验。 此外 解剖学和生理学上的变化，分子 神经元的特性也对早期视觉敏感， 体验. 单克隆抗体Cat-301识别抗原 在LGN Y细胞上，其表达与正常视觉相关， 人生早期的经历 出生时缝合单眼眼睑不仅 抑制Y-的生理和形态发育 细胞在LGN的剥夺层，而且表达 Cat-301抗原在同一细胞上 关键期过后， 单眼眼睑缝合不影响Y细胞形态或 因此，Cat-301抗原不受影响。 这些 结果表明Cat-301抗原的表达 为关键期事件提供了一个阳性分子标记， 视觉系统开发 我们最近的工作表明Cat-301在脊髓中表达， 仓鼠脊髓运动神经元的经验依赖性 方式 正如Cat-301在Y细胞上的表达与正常的 早期视觉经验在仓鼠运动神经元上的表达 与生命早期的正常神经肌肉体验有关。 在成熟期操纵神经肌肉环境， 对Cat-301表达的影响，表明其表达不是 简单地依赖于活动。 在这里，我们建议使用仓鼠脊髓系统的研究， 研究发展的经验依赖特征。 这 系统呈现出许多优势，为研究神经活动 这有助于正常的发展，因为运动单位是 适合药理学解剖，超微结构分析 和体外操作。 药理学研究将测试 运动单位各组成部分对发育的贡献 使用α-银环蛇毒素、秋水仙碱和河豚毒素。 EM研究 将突触发生中的超微结构事件与猫- 301表情和关键期现象。 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在人体运动中表达， 神经元，我们将试图定义一个发展的关键时期， 通过测定Cat-301在人运动神经元中的表达， 不同年代的尸检材料 这些研究旨在增加我们对 依赖经验的发展。 这些知识可能 对损伤后功能恢复的重要意义 发育和成年人CNS。