The role of NG2 cells in the neural network in health and disease

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Loss of myelin and oligodendrocyte dysfunction is being recognized in many neurodegenerative diseases, such as Multiple Sclerosis, Alzheimer's or Parkinson's disease or Epilepsy, although the mechanisms are not yet understood. Oligodendrocytes are generated from NG2 cells, a glial cell population that covers the entire parenchyma of the central nervous system. The multitude of disorders involving oligodendrocyte pathologies in grey and white matter underscores the importance to understand how oligodendrocyte differentiation and myelination are regulated, and the role of NG2 cells therein. The highest density of NG2 cells can be found during the first postnatal weeks, when they differentiate into mature oligodendrocytes ensheathing axons with myelin. NG2 cells retain the capacity for self-renewal throughout life, rendering them a huge regenerative potential in the adult brain. It is still unknown whether all NG2 cells have the same potential to generate oligodendrocytes or whether a subpopulation of them becomes permanent NG2 cells. Neurons form synaptic contacts onto NG2 cells and depolarize them, in order to regulate myelination. Considering the finding, that processes of NG2 glia contact neurons at the node of Ranvier, it could be possible that NG2 cells in turn are able to modulate neuronal activity. To address these questions, this project is designed to investigate how altered neuronal excitability affects the structural and functional relationship between neurons and NG2 cells and how these changes impact the neural network. Using a combination of several cutting-edge techniques, the details of the morphological contact formation as well as the physiological function of these contacts in vivo in models of enhanced neuronal activity will be assessed. The results will be a major contribution to understanding the role of NG2 cells in the neural network in healthy organisms as well as in the numerous diseases where oligodendrocytes are affected.