Oligodendrocyte progenitor cells are paired with GABA neurons in the mouse dorsal cortex: Unbiased stereological analysis

Abstract

Oligodendrocyte progenitor cells (OPC) 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. While adult OPCs form unique territories that are maintained through self-avoidance, some cortical OPCs appear to position their cell body very close to that of a neuron, forming what are known as OPC–neuron pairs. We used unbiased systematic stereological analysis of the NG2-CreERTM:EYFP reporter mouse to determine that close to 170,000 OPC–neuron pairs can be found in the dorsal portion of the adult neocortex, with approximately 40% of OPCs and 4% of neurons in pairs. Through stereological analysis, we also determined that reference memory training does not change the prevalence of OPC–neuron pairs or the proportion of OPCs and neurons that form them. GABAergic agent administration did not affect the proportion of OPCs and neurons that can be found in pairs. However, the GABAB-receptor agonist baclofen and the GABAA receptor antagonist picrotoxin significantly increased the estimated number of pairs when compared to the control group and the GABAB-receptor antagonist (i.e. saclofen) group. Density of OPC–neuron pairs was increased by the GABAA receptor antagonist picrotoxin. Finally, histological analysis of OPC–neuron pairs suggested that in the dorsal portion of the cortex, GABAergic interneurons represent the most common neuronal component of the pairs, and that calbindin, calretinin and parvalbumin GABAergic interneurons found in the cortex take part in these pairs. Using previous estimates of the number of GABAergic neurons in the rodent cortex, we estimate that roughly one in four GABAergic neurons are paired with an OPC.