NEURON DEATH IN CENTRAL NERVOUS SYSTEM DEVELOPMENT

神经元通常过度产生，随后在早期死亡。 发展 我们建议调查这种生产过剩和死亡， 哺乳动物的视网膜，中脑和视觉皮层，以确定哪些因素 有助于神经元的存活 在中脑结构中，上级 我们将操纵传入的数量，并确定两者 突触密度可能变化的范围以及 突触密度降低到细胞死亡 在保留中，我们将确定 一个神经元产生的那一天可以预测它的可能性和时间。 死亡，使用胸苷放射自显影。 对于视觉皮层， 确定它的细胞板层是否对输入和靶向缺失有反应， 就像其他神经结构一样，目的是 确定形态学和细胞数量的局部变化是如何施加的 新皮层的总体计划。 最后，我们将联系的时间， 建立与这些结构之间的联系， 细胞死亡 在所有情况下，我们都将量化可观察到的 在大脑发育的早期， 操纵 总之，我们建议研究早期控制的一个 神经元的存活，并使用有关早期模式的信息 神经元死亡，以告知我们建立的机制， 哺乳动物大脑发育中的有序连接。 这项工作将有 直接关系到我们理解的性质， 在围产期损伤后重组人类大脑。

Neurons are normally overproduced and subsequently die in early development. We propose to investigate this overproduction and death in the mammalian retina, midbrain and visual cortex, to determine what factors contribute to a neuron's survival. In a midbrain structure, the superior colliculus, we will manipulate the amount of afference and determine both the range over which synaptic density may vary and the relationship of synaptic density to cell death. In the retain, we will determine if the day a neuron is generated can predict the likelihood and timing of its death, using thymidine autoradiography. For the visual cortex, we will determine if its cellular laminae respond to input and target deletions in the same way other neural structures have been shown to, with the goal of determining how local variations in morphology and cell number are imposed on the general neocortical plan. Finally, we will relate the timing of establishment of connections to and from these structures to the pattern of cell death. In all cases, we will be quantifying the amount of observable cellular degeneration in early brain development consequent to our manipulations. In sum, we propose to investigate the early control of a neuron's survival and also use the information about the patterns of early neuron death to inform us about the mechanisms of the establishment of orderly connections in the developing mammalian brain. This work will have direct relevance for our understanding of the nature of, and the reasons for, reorganization of the human brain following perinatal damage.