Final Report Summary - ENCODING IN AXONS (Identifying mechanisms of information encoding in myelinated single axons)
The brain is our most complex organ; storing memories and computing actions using electrically active cells organized in highly specific circuits. In order to rapidly and precisely transmit electrical signals over long distances between nerve cells (neurons) a distinct specialized cell type, called the oligodendrocyte, provides electrical insulation by wrapping multiple layers of myelin proteins around the membrane. How these are precisely organized is not well understood. We developed and improved computational and experimental methods to examine fundamental mechanisms of electrical impulse generation and its propagation and tested the hypothesis that there are direct interactions between neurons and oligodendrocytes. The results from this work showed that we highly accurately could reproduce electrical impulses of individual neurons at the sub-micron and -millisecond spatial and temporal resolution, respectively. Furthermore, we also unraveled how myelin is precisely organized relative to the neuronal membrane in order to produce its insulating features. Finally, using animal models we discovered that when myelin is lost, mimicking for example pathological lesions as in multiple sclerosis, impulse generation is maintained but the overall activity of neuronal networks unexpectedly increases. These findings were supported by experiments showing oligodendrocytes takes up ions from active neurons. We conclude that oligodendroglial myelination not only passive insulates but is dynamically integrated in neuron-glia circuits constraining neuronal activity in order to increase temporal precision.