Role of Müller Glial Cells in Synaptic Development and Functioning of the Mammalian Retina

视网膜是研究（周围）突触胶质-神经元相互作用的理想模型系统，因为它具有清晰的组织结构，突触排列在两个丛状层中，并且由于它仅由一种类型的大胶质细胞占主导地位，即与所有神经元隔室接触的m<s:1> ller细胞。基于该领域长期以来的工作，申请人希望在本项目中研究几个问题，即(i)视网膜突触周围胶质鞘是如何在超微结构水平上组织的？（ii）哺乳动物视网膜在适应光/暗的过程中突触及其胶质鞘发生了哪些类型的功能/结构变化？（iii）视网膜突触的活动是如何向突触周围胶质细胞发出信号的？（iv）视网膜突触传递是如何被（例如，神经活性物质的释放）<s:1> ller细胞调节的？研究的主要重点将放在不同的重要染料（包括Ca2+成像和“活性依赖”染料FM1-43）在使用共聚焦显微镜的完整分离的视网膜的整体制备上的应用。此外，将同时进行视网膜神经节细胞和突触细胞的电生理记录。方法范围将由形态学和形态计量学程序（免疫细胞化学，电子显微镜，三维重建）补充；一些研究将在转基因小鼠上进行。该项目的目的是阐明（部分）神经胶质细胞对视网膜信息处理的贡献。

The retina is an ideal model system for studies on (peri-) synaptic glia-neuron interactions since it possesses a clear-cut tissue structure, with the synapses being arranged in the two plexiform layers, and since it is dominated by only one type of macroglia, the Müller cells, which contact all neuronal compartments. Based on long-standing previous work in the field, the applicants want to study several questions in the present project, viz. (i) how are retinal perisynaptic glial sheaths organized at the ultrastructural level?, (ii) what types of functional/structural changes of the synapses and their glial sheaths occur in the mammalian retina during light/dark adaptation?, (iii) how is the activity of retinal synapses signalled to the perisynaptic glial elements?, and, (iv) how is retinal synaptic transmission modulated by (e. g., the release of neuroactive substances from) Müller cells? The main focus of the studies will be on the application of different vital dyes (including Ca2+ imaging and the 'activity-dependent' dye FM1-43) on intact isolated wholemount preparations of the retina, by using confocal microscopy. In addition, simultaneous electrophysiological recordings from retinal ganglion cells and Müller cells will be performed. The range of methods will be supplemented by morphological and morphometrical procedures (immunocytochemistry, electron microscopy, 3-D reconstruction); some studies will be performed on transgenic mice. The aim of the project is to elucidate (some of) the contributions of Müller glial cells to retinal information processing.