MOLECULAR EFFECTS OF EARLY EXPERIENCE ON MOTOR NEURON

在神经发育的关键时期，结构和 中枢神经系统的功能可以被生物体的 与周围环境的相互作用。例如，在猫身上， 背侧正常纹层图案的形成 膝状核(LGN)和眼优势柱 纹状皮质需要正常的早期视觉体验。此外 到解剖和生理变化，分子 神经元的特征对早期视觉也很敏感 经验。单抗Cat-301识别一种抗原 表达与正常视觉相关的LGN Y细胞 在生命的早期经历。出生时单眼眼睑缝合不仅 抑制Y-2的生理和形态发育 在LGN剥夺层中的细胞，也表达 同一细胞上的Cat-301抗原。关键时期过后， 单眼眼睑缝合不影响Y细胞形态或 同样，Cat-301抗原不受影响。这些 研究表明，Cat-301抗原的表达 为临界期事件提供了一个积极的分子标志物 可视化系统开发。 我们最近的研究表明，Cat-301在脊髓上表达 经验依赖型仓鼠脊髓运动神经元 举止。就像Y细胞上Cat-301的表达与正常一样 早期视觉体验及其在仓鼠运动神经元上的表达 与早期生活中正常的神经肌肉体验有关。 在成熟期操纵神经肌肉环境没有 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进行研究 研究依赖经验的发展特征。这 该系统在研究神经活动方面显示出许多优势。 这有助于正常的发展，就像发动机单元一样 药理解剖、超微结构分析 以及体外操作。药理研究将测试 动车组部件对发展的贡献 使用银环蛇毒素、秋水仙碱和河豚毒素。EM研究 将与猫突触发生中的超微结构事件相关联- 301的表达和临界期现象。运动神经元 将开发文化系统来确认和推广这一点 分析。最后，由于Cat-301是在人类运动上表达的 神经元，我们将尝试定义一个发育关键期 通过检测Cat-301在人中的表达对人运动神经元的影响 不同年代的尸检材料。 这些研究旨在增加我们对 依靠经验发展。这一知识可能会 脑损伤后功能恢复的重要意义 发育中和成年人中枢神经系统。

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.