Function of panglial gap junctional networks in mouse brain

• Antragsteller: Professor Dr. Helmut Kettenmann; Professor Dr. Klaus Willecke
• Fachliche Zuordnung: Molekulare Biologie und Physiologie von Nerven- und Gliazellen
• Förderung: Förderung von 2009 bis 2013
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 141293350

Macroglial cells in the central nervous system are coupled via gap junctional connexin (Cx) channels which are thought to establish panglial networks. The extent and the biological function(s) of these panglial networks are largely unknown. Our common project is directed to unravel these functions, including the impact on myelin formation and maintenance. During the current funding period, we could clarify, using Cx30 and Cx47 double deficient mice, that astrocyte to oligodendrocyte (A:O) coupling is necessary to maintain proper myelination and normal morphology of the central nervous system. Furthermore we have established methods to measure coupling between astrocytes and oligodendrocytes by intercellular transfer of microinjected tracer molecules and by patch clamp analyses in acute brain slices. Using these methods we want to characterize three more mouse mutants, each defective in one astrocytic and one oligodendrocytic connexin isoform, in order to systematically interrupt oligodendrocytic-astrocytic coupling In addition, we want to use the mouse mutants to study the impact of coupling on axonal conductance in white matter as well as the impact of induced demyelination on glial coupling. Finally we shall address the question how newly generated oligodendrocytes integrate into the pre-existing network of panglial coupling. Our expected results should allow to distinguish between unique or redundant contribution of each glial connexin isoform to the maintenance of myelin and survival of oligodendrocytes.

• DFG-Verfahren: Sachbeihilfen