Unbiased stereological analysis of the fate of oligodendrocyte progenitor cells in the adult mouse brain and effect of reference memory training

Oligodendrocyte progenitor cells (OPCs) are glial cells that differentiate into myelinating oligodendrocytes during early stages of post-natal life. However, OPCs persist beyond developmental myelination and represent an important population of cycling cells in the gray and white matter of the adult brain. Here, we used unbiased systematic stereological analysis to determine the total number of OPCs in the neocortex and corpus callosum of the adult mouse. We found that the ratio of OPCs to neurons is of 1:10 in the adult neocortex. Likewise, the ratio of OPCs to oligodendrocytes is of 1:1 in the cortex and 1:7 in the corpus callosum. We also used BrdU labeling and the NG2-CreER™:EYFP reporter mouse to determine the proportion of proliferating adult OPCs and their fate. We show that OPCs continue to differentiate into oligodendrocytes in adulthood, with white matter OPCs being more likely to differentiate into an oligodendrocyte phenotype than gray matter OPCs. The differentiation of OPCs into an oligodendrocyte phenotype can occur either directly from a spontaneous differentiation by an OPC or following OPC cell division. We also provide evidence for the neuronal differentiation of adult OPCs in the cortical gray matter. Although activity-dependent neural network activity has been hypothesized to serve as a modulator of OPC proliferation and differentiation, we found that reference memory training did not affect the proportion of proliferating and differentiated OPCs in the adult mouse brain.