Panglial coupling and the metabolic support of axons and synapses

神经胶质细胞耦合以及轴突和突触的代谢支持

• 批准号: 235153551
• 负责人: Professor Dr. Christian Steinhäuser
• 金额: --
• 依托单位: Max-Delbrück-Centrum für Molekulare Medizin (MDC) in der Helmholtz-Gemeinschaft
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/235153551?language=en
• 关键词: Panglial; coupling; metabolic; support; axons

Astrocytes and oligodendrocytes, the macroglial cells of the central nervous system, are coupled by gap junctions. The common project of the groups of Christian Steinhäuser, Bonn, and Helmut Kettenmann / Christiane Nolte, Berlin, is based on a long term cooperation in which we characterized the properties of the panglial network and determined its importance for neuronal functions. Our recent findings in the corpus callosum point to distinct mechanisms of neuron-glial metabolic cooperation in white matter, which differs from the current concept of glia-neuronal lactate shuttling as described for the optic nerve. Our work in the thalamus has revealed an unexpected pattern and extent of panglial coupling, which raises the question of the role of oligodendrocytes in fueling synaptic activity. In the present project we plan to analyze the importance of gap junction coupling for the metabolic interaction between glial cells and neurons. We load metabolites like lactate or glucose into single glial cells, both astrocytes and oligodendrocytes, via a patch pipette and analyze how this loading can rescue neuronal activity after extracellular glucose depletion. We analyze the relative contribution and impact of astrocytes and oligodendrocytes of the panglial network for this metabolic interaction and compare underlying mechanisms in different tissues of white and grey matter. Previous studies have shown that metabolic interactions are controlled by neurotransmitters, and therefore we study the regulation of panglial coupling by these signaling molecules. The planned experiments aim at a better understanding of the coordinated activity of neurons and glial cells in the central nervous system.

星形胶质细胞和少突胶质细胞是中枢神经系统的大胶质细胞，它们通过缝隙连接连接。波恩的Christian Steinhäuser和柏林的Helmut Kettenmann / Christiane Nolte团队的共同项目是基于长期合作，我们描述了panglial网络的特性并确定了其对神经元功能的重要性。我们最近在胼胝体中的发现指出了白色物质中神经元-神经胶质细胞代谢合作的不同机制，这不同于目前针对视神经描述的神经胶质细胞-神经元乳酸穿梭的概念。我们在丘脑中的工作揭示了一种意想不到的模式和程度的panglial耦合，这提出了少突胶质细胞在促进突触活动中的作用的问题。在本项目中，我们计划分析神经胶质细胞和神经元之间的代谢相互作用的间隙连接耦合的重要性。我们通过贴片移液管将乳酸或葡萄糖等代谢产物加载到单个胶质细胞（星形胶质细胞和少突胶质细胞）中，并分析这种加载如何在细胞外葡萄糖耗尽后挽救神经元活性。我们分析了星形胶质细胞和少突胶质细胞的panglial网络的这种代谢相互作用的相对贡献和影响，并比较了白色和灰质不同组织的潜在机制。先前的研究表明，代谢相互作用是由神经递质控制的，因此我们研究这些信号分子对神经节耦合的调节。计划中的实验旨在更好地了解中枢神经系统中神经元和神经胶质细胞的协调活动。