Hochauflösendes konfokales Fluoreszenz-Mikroskop mit STED-Technologie

采用 STED 技术的高分辨率共焦荧光显微镜

• 批准号: 414012445
• 金额: --
• 依托单位: Technische Universität Braunschweig
• 依托单位国家: 德国
• 项目类别: Major Research Instrumentation
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 无数据
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/414012445?language=en
• 关键词: Hochaufl; sendes; konfokales; Fluoreszenz; Mikroskop

Functional and structural changes at synapses (plasticity) have been shown to underlie learning and memory processes. A very precise balance between plasticity and stability of synapses and thereby of the mature CNS network is crucial to ensure learning and memory formation. Thus, it is of crucial interest to analyse changes in the architecture of dendritic spines, the site of most excitatory synapses and to correlate them to functional changes. In addition, synaptic localization of molecules involved in synaptic transmission and plasticity is of extreme interest. In particular, it is of prime importance to analyse activity-dependent changes in the localization of plasticity-promoting (e.g. BDNF) or plasticity-limiting (e.g. Nogo-A) proteins and their consequences on spine/synapse structure. However, the imaging methods used so far suffer from intrinsic limitations that do not allow to resolve changes occurring below optical resolution. Combining confocal-based super-resolution (HyVolution) and Nanoscopy (Stimulated Emission Depletion, STED) will allow us to analyse structural plasticity upon learning, molecular mechanisms regulating it and its functional consequences. The combination of HyVolution and STED will allow us to analyse changes in size and shape of synaptic structures as well as protein/mRNA localization relative to the synapses under physiological (learning) or pathological conditions (Alzheimer, mental retardation, neuroinflammation).

突触（可塑性）的功能和结构变化已被证明是学习和记忆过程的基础。突触的可塑性与稳定性之间的平衡以及成熟的CNS网络的稳定性对于确保学习和记忆形成至关重要。因此，分析树突状棘的结构的变化，这是至关重要的，这是大多数兴奋性突触的部位，并将它们与功能变化相关联。此外，与突触传递和可塑性有关的分子的突触定位非常有趣。特别是，分析促进性促进性（例如BDNF）或可塑性限制（例如Nogo-A）蛋白质及其对脊柱/突触结构的后果的依赖活性依赖性变化至关重要。但是，到目前为止使用的成像方法遭受了固有的局限性，这些局限性不允许解决低于光学分辨率的变化。将基于共聚焦的超分辨率（Hyvolution）和纳米镜检查（刺激的发射消耗，Sted）结合在一起，将使我们能够在学习时分析结构可塑性，调节其功能后果的分子机制。 Hyvolution and Sted的组合将使我们能够分析突触结构的大小和形状的变化，以及相对于生理（学习）或病理条件下突触（阿尔茨海默氏症，心理迟缓，神经毒素）下的突触的蛋白质/mRNA定位。