Calcium, proliferation and AMPA receptors in NG2 glial cells
Final Report Abstract
Oligodendrocyte precursor cells, or NG2 cells, generate oligodendrocytes, which myelinate axons and thereby support and enable normal brain function and plasticity. There is accumulating evidence that myelination may be modulated by neuronal activity, however the underlying mechanisms are still unresolved. As there are several neurological disorders associated with myelin loss and syndromes with damage of white matter in pre-term infants an improved understanding is necessary. Here, we used mouse brain slices and in vivo experiments with transgenic mice and identified a critical period in early postnatal life during which NG2 gilal cells are very susceptible to intracellular calcium overloads caused by neuronal activity. Such calcium overload can be induced by genetic deletion of an AMPA receptors subunit (GluA2) which normally limits calcium entry during synaptic activation of NG2 cells by neurons. Oligodendrocytes derived from GluA2-deficient NG2 cells are impaired in establishing myelin sheaths around axons during postnatal development. As a consequence, mice experience motor learning deficits likely due to unoptimized networks. Proliferation and differentiation of NG2 cells was found to be unaltered by increased calcium signaling and deletion of GluA2. Our data show that the effect of neuronal activity to guide the development of oligodendroglial cells needs to be finely dosed and when unbalanced it can have detrimental effects on brain development resulting in lasting deficits on the behavioral level. Our results further emphasize the susceptibility of the early postnatal brain and that also alterations of signaling exclusively in glial cells can lead to a maldevelopment of neuronal circuits.
Publications
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(2016). NG2 glial cells integrate synaptic input in global and dendritic calcium signals. ELife 5
Sun, W., Matthews, E.A., Nicolas, V., Schoch, S., and Dietrich, D.
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(2017). Transient Cnp expression by early progenitors causes Cre-Lox-based reporter lines to map profoundly different fates. Glia 65, 342–359
Tognatta, R., Sun, W., Goebbels, S., Nave, K.-A., Nishiyama, A., Schoch, S., Dimou, L., and Dietrich, D.
