DEVELOPMENT OF SENSORY/MOTOR SYNAPSES IN THE SPINAL CORD

描述：神经系统的正确运行取决于 轴突投射和突触的高度特异性模式的形成 神经细胞之间的连接。要了解这种情况是如何发生的， 该方案所采取的方法是研究一口井的开发。 详细描述了神经元的电路，简单的单突触 伸展反射。供应牵张敏感纺锤的感觉神经元 肌肉中的器官(Ia传入)投射到脊髓，在那里它们 与特定的神经元亚群建立高度特异的突触联系 运动神经元。这里提出的实验考察了每个方面是如何 这种感觉通路的发展是受控制的：最初的 Ia传入神经的分化及其对其生存的支持 外周或中心靶标因子，负责 IA轴突开始长入脊髓，在这些引导下 轴突朝向腹角，最后它们的树枝和 与运动神经元形成功能性突触。这些问题是 阐述了用两种不同的实验制剂进行显影 鸡胚：脊髓和感觉神经节的器官培养 将允许详细研究Ia预测的发展情况 以比活体中可能的更高的分辨率绘制图案。一个平行的 对完整的、经过手术处理的胚胎进行的一系列实验将检查 如果培养的结果也适用于更正常的发育 活着。最后将开发一个类似的器官类型培养系统。 使用胚胎小鼠来测试这些发现在 哺乳动物系统。 这项建议的六个具体目标是：(1)确定NT-3是否 指导Ia感觉神经元的分化，(2)分析 运动神经元和外周靶肌肉在中枢神经系统中的相对作用 控制Ia传入的数量；(3)分析内隐线索 引导Ia轴突从背根穿过背侧的脊髓 角至腹索，(4)确定性质和身份 脊髓内促进Ia轴突树枝形成的信号 腹角，(5)分析外周靶点在脑电活动中的作用。 Ia轴突间特定突触连接模式的形成 和运动神经元，以及(6)开发一种类似的制备培养的 胚胎小鼠的脊椎外植体。

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.