Pacemakers of Cholinergic Wave Activity in the Developing Retina

项目总结 在视觉出现之前，自发的视网膜波活动对于视网膜层特异性是必不可少的。 视网膜神经节细胞的血管生成和树突成熟，以及眼睛特异的 种族隔离和复视地图。视网膜无长突中间神经元的一个亚群，称为星爆型无长突 细胞通过称为胆碱能视网膜的经常性胆碱能连接启动和传播视网膜波 海浪。然而，胆碱能波的启动和传播机制尚不清楚。 目前，最紧迫的优先事项是定义胆碱能波是如何启动的，以创建一个框架 了解它们的下行传播。该项目的目标是确定星暴长寿的一个子集 用作胆碱能波起搏器的细胞及起搏器星爆无长突细胞的机制 细胞产生这些波。来自PI实验室的初步数据表明，识别 起搏器星爆无长突细胞与单个起搏器星爆无长突细胞启动的充分性 一个浪头。波形的产生需要激活电压依赖的钙通道。这些新的发现导致了 中心假说：单个起搏器星状突起的无长突细胞通过钙依赖的 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机制(目标2)。 了解起搏星状突起无长突细胞和离子的身份和特征的工作 胆碱能视网膜波的产生机制将促进对视网膜波如何调节的认识 视网膜的血管和神经元发育以及眼的特异性分离和视网膜定位图 大脑视觉中心的精炼。

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.