DEVELOPMENT OF SENSORY/MOTOR SYNAPSES IN THE SPINAL CORD

脊髓中感觉/运动突触的发育

• 批准号: 2891695
• 负责人: ERIC FRANK
• 金额: $ 31.25万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-04-01 至 2001-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2891695
• 关键词: chick embryo; developmental neurobiology; dorsal root; embryo /fetus tissue /cell culture; innervation; laboratory mouse; motor neurons; neurogenesis; neuromuscular junction; neuromuscular transmission; neuronal guidance; neurophysiology; spinal cord; stretch reflex; synaptogenesis; tissue /cell culture

DESCRIPTION: The correct operation of the nervous system depends on the formation of highly specific patterns of axonal projections and synaptic connections among nerve cells. To understand how this occurs, the approach taken in this proposal is to study the development of one well characterized neuronal circuit in detail, the simple monosynaptic stretch reflex. Sensory neurons supplying stretch-sensitive spindle organs in muscles (Ia afferents) project into the spinal cord where they make highly specific synaptic connections with particular subsets of motoneurons. The experiments proposed here examine how each aspect of the development of this sensory pathway is controlled: the initial differentiation of Ia afferents and the support of their survival by peripheral or central target factors, the molecular cues responsible for Ia axons to begin growing into the spinal cord, the guidance of these axons towards the ventral horn, and finally their arborization and the formation of functional synapses with motoneurons. These issues are addressed using two different experimental preparations of the developing chicken embryo: Organotypic cultures of spinal cord and sensory ganglia will permit the detailed study of the development of Ia projection patterns at a higher resolution than is possible in vivo. A parallel set of experiment on intact, surgically manipulated embryos will check if the results from culture also apply to more normal development in vivo. Finally an analogous organotypic culture system will be developed using embryonic mice to test the generality of these findings in a mammalian system. The six specific aims of this proposal are: (1) to determine if NT-3 instructs the differentiation of Ia sensory neurons, (2) analyze the relative roles of motoneurons and peripheral target muscle in controlling the number of Ia afferents, (3) analyze the cues within the spinal cord that guide Ia axons from the dorsal roots through the dorsal horn to the ventral cord, (4) determine the nature and identity of signals within the spinal cord that promote arborization of Ia axons in the ventral horn, (5) analyze the role of peripheral targets on the formation of specific patterns of synaptic connections between Ia axons and motoneurons, and (6) develop an analogous preparation of cultured spinal explants from embryonic mice.

描述：神经系统的正确运作取决于 形成高度特异性的轴突投射和突触模式 神经细胞之间的联系。 为了了解这是如何发生的， 本提案采取的方法是研究一口井的开发 详细描述了神经元回路，简单的单突触 牵张反射。 感觉神经元提供拉伸敏感纺锤体 肌肉中的器官（Ia 传入神经）投射到脊髓中，在那里它们 与特定子集建立高度特异性的突触连接 运动神经元。 这里提出的实验检验了每个方面如何 这种感觉通路的发展是受控的：最初 Ia 传入神经的分化及其生存的支持 外周或中心目标因素，负责的分子线索 Ia 轴突开始生长进入脊髓，这些的引导 轴突朝向腹角，最后是它们的树枝化和 与运动神经元形成功能性突触。 这些问题是 使用两种不同的开发实验制剂来解决 鸡胚胎：脊髓和感觉神经节的器官型培养 将允许详细研究 Ia 投影的发展 模式的分辨率比体内可能的分辨率更高。 平行 一组对完整的、经过手术操作的胚胎进行的实验将检查 如果文化的结果也适用于更正常的发展 体内。 最终将开发出类似的器官型培养系统 使用胚胎小鼠来测试这些发现的普遍性 哺乳动物系统。 该提案的六个具体目标是： (1) 确定 NT-3 是否 指导 Ia 感觉神经元的分化，（2）分析 运动神经元和外周目标肌肉的相对作用 控制 Ia 传入神经的数量，(3) 分析 Ia 传入神经的数量 脊髓引导 Ia 轴突从背根穿过背侧 角到腹侧索，（4）确定其性质和身份 脊髓内促进 Ia 轴突分枝的信号 腹角，（5）分析周围目标对腹角的作用 Ia 轴突之间突触连接特定模式的形成 和运动神经元，以及（6）开发培养的类似制剂 来自胚胎小鼠的脊柱外植体。