Back

Early developmental neuronal activity inhibits oligodendrocyte differentiation through AMPA receptor activation

Allen, T.; Peet, G.; Gomez Wulschner, L.; Oh, W. C.; Macklin, W.

2025-10-17 neuroscience
10.1101/2025.10.17.683139 bioRxiv
Show abstract

Oligodendrocytes produce myelin, a lipid-rich membrane that wraps neuronal axons in the central nervous system to provide metabolic and trophic support and allow for saltatory conduction. Developmental myelination requires precisely timed and localized neuron-oligodendrocyte communication. In the mature brain, neuronal activity promotes oligodendrocyte precursor cell (OPC) proliferation and differentiation, but how OPCs respond to neuronal activity in early brain development, prior to the onset of myelination, is less well characterized. Here, we investigate how sensory-evoked and chemogenetically altered neuronal activity affect oligodendrocyte maturation in the olfactory system, somatosensory cortex, and corpus callosum in mice. We find that early neuronal activity inhibits oligodendrocyte differentiation and that reduced neuronal activity relieves this inhibition, thereby increasing OPC differentiation. Additionally, single-cell RNA sequencing revealed transcriptional changes in oligodendrocytes when neuronal activity was reduced, including upregulation of glutamate receptor gene expression. Finally, we identify AMPAR signaling as a critical regulator of oligodendrocyte differentiation ex vivo.

Matching journals

The top 5 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.