Pacemakers of Cholinergic Wave Activity in the Developing Retina

项目摘要 在视觉出现之前，自发性视网膜波活动是视网膜层特异性的 血管生成和视网膜神经节细胞的树突成熟，以及用于细化眼睛特异性 分离和视网膜定位图。视网膜无长突中间神经元的一个亚群，称为星状无长突 细胞，启动和传播视网膜波通过经常性的胆碱能连接称为胆碱能视网膜 波然而，胆碱能波的启动和传播的机制还不清楚。 目前，最紧迫的优先事项是确定胆碱能波是如何启动的，以建立一个框架， 了解其下游传播。这个项目的目标是确定一个子集的星爆无长突 细胞作为胆碱能波起搏器和起搏器星爆无长突的机制 细胞产生这些波。PI实验室的初步数据表明， 起搏星状突无长突细胞和单个起搏星状突无长突细胞启动 一个波浪。波的产生需要激活电压依赖性钙通道。这些新发现导致 中心假设：单个起搏点星状突无长突细胞通过钙依赖性 机制为了验证这一假设，研究小组将确定胆碱能波的分布和性质， 起搏器（目标1），并确定胆碱能波产生的钙依赖性机制（目标2）。 了解起搏星状突无长突细胞的身份和特征的工作和离子 胆碱能视网膜波产生的机制将推进视网膜波如何介导的知识 视网膜的血管和神经元发育以及眼特异性分离和视网膜定位图 大脑视觉中枢的精细化。

PROJECT SUMMARY Before the emergence of vision, spontaneous retinal wave activity is essential for retinal layer-specific angiogenesis and dendritic maturation of retinal ganglion cells, as well as for the refinement of eye-specific segregations and retinotopic maps. A subpopulation of retinal amacrine interneurons, called starburst amacrine cells, initiate and propagate retinal waves through recurrent cholinergic connections called cholinergic retinal waves. However, the mechanisms underlying cholinergic wave initiation and propagation are poorly defined. Currently, the most urgent priority is to define how cholinergic waves are initiated to create a framework for understanding their downstream propagation. This project's objective is to identify a subset of starburst amacrine cells that serve as cholinergic wave pacemakers and the mechanisms by which pacemaker starburst amacrine cells generate these waves. Preliminary data from the PI's laboratory demonstrate that it is feasible to identify pacemaker starburst amacrine cells and the sufficiency of a single pacemaker starburst amacrine cell to initiate a wave. Wave generation requires activation of voltage-dependent calcium channels. These novel findings lead to the central hypothesis: single pacemaker starburst amacrine cells initiate waves by a calcium-dependent mechanism. To test this hypothesis, the team will determine the distribution and properties of cholinergic wave pacemakers (Aim 1), and identify the calcium-dependent mechanisms of cholinergic wave generation (Aim 2). The work on understanding the identity and features of pacemaker starburst amacrine cells and the ionic mechanisms of cholinergic retinal wave generation will advance knowledge of how retinal waves mediate vascular and neuronal development of the retina as well as eye-specific segregation and retinotopic map refinement in the visual centers of the brain.