Role of GluA2-Containing AMPA-Receptors in NG2 cells

Vicky Nicolas1, Abigail Calder1, Susanne Schoch2, Dirk Dietrich1

1 Department of Neurosurgery/University Clinic Bonn, Germany
2 Department of Neuropathology/University Clinic Bonn, Germany

Oligodendrocyte precursor cells, NG2 cells, can proliferate and differentiate into myelin-producing oligodendrocytes throughout life. While it has been established that neuronal activity influences the speed and degree of axon myelination, the factors mediating activity-dependent control of proliferation and differentiation of NG2 cells have not been resolved yet. Interestingly, NG2 cells receive direct synaptic input from neurons throughout the CNS. The fast vesicular glutamatergic input is mainly mediated by AMPA receptors. During the postnatal period these AMPA receptors contain the GluA2 subunit, which renders them calcium-impermeable, but later in life, NG2 cells downregulate the GluA2 subunit. Thus, the decline of the proliferation rate of NG2 cells observed during the transition from the postnatal to the adult period is mirrored by an increase in calcium- permeability of synaptic AMPA-receptors. We hypothesized that calcium signals in NG2 cells reduce their proliferation rate and that the role of postnatally expressed GluA2 subunits is to allow the proliferation of NG2 cells by suppressing calcium entry during synaptic activity. Here, we assess the impact of the deletion of the GluA2 subunit on the NG2 cell lineage. In order to induce a conditional deletion of the GluA2 subunit specifically in NG2 cells, we crossed NG2CreER, GluA2lox, and R26REYFP mouse lines. Cre expression was induced via tamoxifen (TMX) injection at the 4th postnatal day (PND). We labeled proliferating cells (in S-phase), 7 days after TMX injection, using a triple injection of Bromodeoxyuridine (BrdU). The proliferative fraction of recombined NG2 cells (NG2+YFP+BrdU+/NG2+YFP+) was revealed by immunohistochemistry.