Function of Neural Activity in Developing Retina

描述（申请人提供）：自发性的机制和功能 将研究发育中的哺乳动物视网膜中的神经活动。不成熟 视网膜神经元自发地以波的形式产生相关活动 扫描视网膜神经节细胞层的动作电位。这些 “视网膜波”发生在视网膜神经节发育期， 细胞轴突在外侧膝状体中分离成眼特异性层 原子核使用光学成像，电生理学和 模型提出了研究细胞间耦合的机制， 视网膜波传播的基础。此外，药理学 显著改变相关放电模式的操作 通过视网膜波和缺乏视网膜波的转基因小鼠将被用于 研究它们在视网膜向外侧投射的发展中的作用。 膝状体核这项工作的一个结果将是确定关键的 用于驱动的视网膜波所产生的活动模式的参数 活动依赖的发展过程。这项工作将检验这一假设 自发的、相互关联的活动负责组织 神经系统发育中的突触，并将导致进一步的 了解活动依赖性的细胞和分子基础 在视觉系统的发展过程中。这项工作将进一步促进我们的 理解支配正常发展的组织原则 人类神经系统的起源，使人们有可能了解 神经性先天缺陷，并制定策略， 系统在受伤后再生功能神经回路。

DESCRIPTION (Provided by applicant): The mechanisms and function of spontaneous neural activity in the developing mammalian retina will be studied. Immature retinal neurons spontaneously generate correlated activity in the form of waves of action potentials that sweep across the retinal ganglion cell layer. These "retinal waves" occur during the developmental period when retinal ganglion cell axons are segregating into eye-specific layers in the lateral geniculate nucleus. Experiments using a combination optical imaging, electrophysiology and modeling are proposed to investigate the mechanisms of intercellular coupling that underlie the propagation of retinal waves. In addition, pharmacological manipulations that significantly alter the correlated firing patterns induced by retinal waves and transgenic mice lacking retinal waves will be used to investigate their role in the development of retinal projections to the lateral geniculate nucleus. One result of this work will be to determine the critical parameters of the activity patterns generated by retinal waves for driving activity dependent developmental processes. This work will test the hypothesis that spontaneous, correlated activity is responsible for proper organization of synapses in the developing nervous system and will lead to a further understanding of the cellular and molecular basis for activity-dependent processes in the developing visual system. This work should further our understanding of the organizing principles that govern the normal development of the human nervous system, making it possible to understand the origin of neurological birth defects and to devise strategies that allow the nervous system to regenerate functioning neural circuits after injury.