Panglial coupling and the metabolic support of axons and synapses

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，通过缝隙连接连接。波恩的Christian Steinhäuser和柏林的Helmut Kettenmann/Christian Nolte小组的共同项目是建立在长期合作的基础上的，在合作中，我们表征了盘状网络的属性，并确定了其对神经元功能的重要性。我们的最新发现指出白质中神经元-神经胶质代谢的不同机制，这不同于目前对视神经所描述的神经胶质-神经元乳酸穿梭的概念。我们在丘脑的研究揭示了一种意想不到的苍白球连接模式和程度，这引发了少突胶质细胞在促进突触活动中所扮演的角色的问题。在本项目中，我们计划分析缝隙连接耦合在神经胶质细胞和神经元之间代谢相互作用中的重要性。我们通过贴片吸管将乳酸或葡萄糖等代谢物加载到单个胶质细胞中，包括星形胶质细胞和少突胶质细胞，并分析这种加载如何在细胞外葡萄糖耗尽后恢复神经元的活动。我们分析了苍白质网络中星形胶质细胞和少突胶质细胞对这种代谢相互作用的相对贡献和影响，并比较了白质和灰质不同组织的潜在机制。以前的研究表明，代谢相互作用受神经递质控制，因此我们研究了这些信号分子对苍白球偶联的调节。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。

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.