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Early Developmental Neuronal Activity Impacts Oligodendrocyte Differentiation Through AMPA Receptors

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, before the onset of myelination, is less well characterized. Here, we investigate how glutamatergic neuronal activity regulates early developmental oligodendrocyte maturation in the olfactory system, somatosensory cortex, and corpus callosum in mice. We find that decreased neuronal activity increases oligodendrocyte differentiation in early development, both in a sensory deprivation model and when using in vivo chemogenetics. Conversely, enhanced neuronal activity in early development reduces oligodendrocyte differentiation. Additionally, single-cell RNA sequencing revealed transcriptional changes in oligodendrocytes when neuronal activity was reduced, including upregulation of glutamate receptor gene expression and pathways relating to synapse development. Finally, using ex vivo cortical slice culture, we identify AMPAR signaling as a critical regulator of the later steps of oligodendrocyte maturation, but not the initiation of differentiation.

ORGANISM(S): Mus musculus

PROVIDER: GSE329995 | GEO | 2026/06/01

REPOSITORIES: GEO

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