Hochauflösendes konfokales Fluoreszenz-Mikroskop mit STED-Technologie
Hochauflösendes konfokales Fluoreszenz-Mikroskop mit STED-Technologie
批准号:
414012445
负责人:
金额:
$0.0万
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
项目状态:
未结题
起止时间:
2017-12-31 至 --
中文摘要
突触的功能和结构变化(可塑性)已被证明是学习和记忆过程的基础。突触的可塑性和稳定性之间的非常精确的平衡,从而成熟的中枢神经系统网络是至关重要的,以确保学习和记忆的形成。因此,它是至关重要的利益,以分析的树突棘,最兴奋性突触的网站的架构的变化,并将它们与功能的变化。此外,参与突触传递和可塑性的分子的突触定位是极其感兴趣的。特别是,它是最重要的是分析活动依赖性的变化,在本地化的可塑性促进(如BDNF)或可塑性限制(如Nogo-A)蛋白质及其后果的脊柱/突触结构。然而,到目前为止使用的成像方法受到固有的限制,不允许解决低于光学分辨率发生的变化。结合基于共焦的超分辨率(HyVolution)和纳米镜(受激发射损耗,STED)将使我们能够分析学习时的结构可塑性,调节它的分子机制及其功能后果。HyVolution和STED的结合将使我们能够分析突触结构的大小和形状的变化,以及在生理(学习)或病理条件下(阿尔茨海默病,精神发育迟滞,神经炎症)相对于突触的蛋白质/mRNA定位。
英文摘要
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).
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