We are studying the interactions of neurons and glial cells in the mammalian nervous system with a special interest in the role of oligodendrocytes and Schwann cells, best known as myelin forming cells of the central and peripheral nervous system. These highly specialized glial cells enwrap axons with a multilayered sheath that provides electrical insulation for rapid impulse propagation. However the biology of these axon-glia interactions is complex. Using mouse genetics, originally to study the role of proteins in the myelin architecture and in neurogenetic disorders, we made the unexpected discovery of a novel function of oligodendrocytes, which even precedes myelin in nervous system evolution: the glial metabolic support of axonal conduction, axonal transport and long-term integrity. We determined that oligodendrocytes and Schwann cells take up glucose and deliver lactate, here the product of aerobic glycolysis, to the axonal compartment. This supportive function helps maintaining axon functions especially when ATP demands are increased at higher firing rates, also because access of axons to extracellular metabolites is restricted by myelin itself. Here, the fine architecture of the myelin sheath that we visualize with advanced electron microscopic techniques appears critical. Specialized cytoplasmic connections within the myelin sheath (‘myelinic nanochannels’) must provide a pathway of continuous communication between oligodendrocytes and the encapsulated axon. In neurological diseases, in which myelin is structurally affected or even destroyed, such as in multiple scleroses, leukodystrophies and various peripheral neuropathies, there is invariably secondary axonal degeneration that we propose is caused by the lack of adequate metabolic support. We are investigating the underlying molecular mechanisms of these diseases in detail, using corresponding animal models that we have generated with a range of genetic techniques. A further goal is to understand the role of myelinating glial cells in higher brain functions and psychiatric diseases, which we approach in close collaboration with the Department of Hannelore Ehrenreich at our institute.