Panglial coupling and the metabolic support of axons and synapses

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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.