ORDER OF NEUROGENESIS AND PATTERNS OF NERVE CONNECTIONS

我们建议检验这样一个假设，即神经元的精确时间顺序 生产和先到先得原则是必不可少的 保证地形神经有序发育的因素 关系。具体地，关于发送器结构的哪些光纤将 第一个或最后一个到达目标位置，以及哪个感受器神经元将是第一个 或者到达光纤的最后可用时间将不仅取决于时间 结构内部和结构之间的神经元产生顺序，但也在 它们内部和之间的空间关系。因此，它是假定的 先到先得原则可以有四种基本形式： (I)时间-时间(最早发送者神经元与最早接收者联系 神经元，反之亦然)；(Ii)时间-空间(最早的发送神经元 联系最近的接收神经元)；(3)时空 (最接近最早的连接)，以及(Iv)空间-空间 (最近的连接)。将进行三项主要研究 来检验这一假设。首先，我们将完成规范的断代 整个大鼠神经系统神经元的出生日期，使用 新的、逐渐延迟的累积标签程序。这些结构 定量评估将包括耳蜗、眼、背根 神经节和新皮质的特定区域。第二，在 甲基丙烯酸酯包埋的完整胚胎我们将(I)定位神经上皮 与成人神经遗传区相对应的区域 胸腺嘧啶核苷放射摄影术；(Ii)追踪年轻神经元的迁移路径 从前者到后者；以及(Iii)早期发展的日期 纤维束并追踪它们的轨迹。第三，试图 对先到先得的运作方式进行实验评估 原理，HRP和其他示踪剂将被注射到选定的中央和 不同胎龄胚胎的外周结构。这些结构将 包括前肢和后肢，颈髓和腰髓， 新皮质的感觉区域和运动区的特定区域， 眼睛，如果可能的话，还有内耳。

We propose to test the hypothesis that the precise temporal order of neuron production and the first come - first served principle are essential factors in assuring the development of orderly topographic nerve connections. Specifically, as to which fibers of a sender structure will reach a target site first or last and which receiver neurons will be first or last available to arriving fibers will depend not only on the temporal order of neuron production within and between structures but also on the spatial relations within and between them. Therefore, it is postulated that the first come - first served principle may take four basic forms: (i) temporo-temporal (earliest sender neurons contacting earliest receiver neurons, and vice versa); (ii) temporo-spatial (earliest sender neurons contacting nearest receiver neurons); (iii) spatio-temporal (nearest-to-earliest connections), and (iv) spatio-spatial (nearest-to-nearest connections). Three major studies will be carried out to test this hypothesis. First, we will complete the normative dating of the birth dates of neurons throughout the rat nervous system, using the new, progressively delayed cumulative labeling procedure. The structures evaluated quantitatively will include the cochlea, the eye, the dorsal root ganglia, and specific areas of the neocortex. Second, in methacrylate-embedded whole embryos we will (i) locate the neuroepithelial zones that correspond to the neurogenetic zones identified in adults with thymidine-radiography; (ii) trace the migratory paths of young neurons from the former to the latter regions; and (iii) date the outgrowth of early fiber tracts and trace their trajectories. Third, in an attempt to experimentally evaluate the operation of the first come - first served principle, HRP and other tracers will be injected into selected central and peripheral structures in embryos of different ages. These structures will include the forelimbs and hind limbs, the cervial and lumbar spinal cord, specific regions of the sensory areas and the motor area of the neocortex, the eye, and, if possible, the inner ear.