Abstract
Oligodendrocyte precursor cells (OPCs) can generate myelinating oligodendrocytes life-long, a process that is dependent on neuronal activity. However, it is possible that OPCs have additional functions, influencing neuronal functions directly. We have used a mouse genetic model of juvenile seizures and chemical induction of neuronal activity to examine the morphological and molecular changes in OPCs around activated principal neurons. We found an increase in process extension of OPCs specifically toward the soma of activated neurons. Moreover, we found that the close proximity of OPC processes around neurons expressing the immediate early gene c-Fos decreased the calcium transients in these neurons, indicating a regulative function of OPCs. Analyses of transcriptome and chromatin accessibility revealed significant changes in genes involved in transforming growth factor beta (TGFβ) signaling. Extracellular matrix genes, particularly those encoding type VI collagen, an established binding partner for the OPC surface protein NG2, was increased around active neurons. Our findings indicate that OPCs are an integral part of the neural network and may help to decrease the activity of neurons that have previously been over-excited, in order to protect these neurons.