Calcium, proliferation and AMPA receptors in NG2 glial cells

• Applicants: Professor Dr. Dirk Dietrich; Professorin Dr. Susanne Schoch McGovern
• Subject Area: Molecular and Cellular Neurology and Neuropathology
• Term: from 2008 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 94577405

Proper function of the central nervous system requires precise timing of the activity of neuron ensembles. Precise timing of the activity of remote neurons can only be achieved if electrical isolation of neuronal processes, provided by so called myelin sheathes, accelerates the conduction of single impulses. Importantly, myelin sheathes cannot be produced by neurons themselves but they arise through an intricate, not well understood interaction between neuronal processes, the axons, and a specialized type of glial cells, the oligodendrocytes. During development oligodendrocytes have to be generated in the required number to match the number of axons present and they have to recognize and contact axons in their immediate vicinity. Furthermore, it is known that electrical activity of axons supports the generation of oligodendrocytes and accelerates the production of myelin sheathes. However, it is currently unclear how oligodendroglial cells may sense the electrical activity of axons. Our previous work demonstrated that neurites are able to release neurotransmitter onto precursor cells of oligodendrocytes. Further, removal of the required neurotransmitter receptor from oligodendrocyte precursor cells lead to a drop in the division rate. Here we will test the hypothesis that transmitter release from neurites causes calcium signals in oligodendrocyte precursor cells which in turn controls their proliferation. To this end we have developed and verified a dedicated transgenic mouse model with which we will test our hypothesis in a loss- and gain-of-function analysis based on electrophysiological and cell biological techniques. We expect that our results will shed light on fundamental aspects regarding the generation of oligodendrocytes and that they will improve the understanding and treatment of chronic demyelinating disorders.

• DFG Programme: Research Grants