Temporal dynamics and heterogeneity of oligodendrocytes lineage responses to intracortical electrode implantation

Objective. Implantable neural electrodes are essential tools for recording brain activity, yet their long-term performance is often compromised by neuroinflammatory responses following implantation. Although glial scar formation is known to contribute to signal deterioration, the involvement of oligodendrocytes lineage cells in the tissue response remains poorly understood. This study aims to characterize the temporal dynamics and functional heterogeneity of oligodendrocyte lineage cells at the electrode-brain interface.Approach. We performed single-nucleus transcriptomics single-nucleus RNA sequencing on rat cortical tissue surrounding implanted neural electrodes at acute (3 d), subacute (25 d), and chronic (50 d) stages. We focused on oligodendrocyte precursor cells (OPCs), newly formed oligodendrocytes, and mature oligodendrocytes to investigate their transcriptional changes, differentiation trajectories, and intercellular communication networks.Main results. Acute implantation induced metabolic activation and stress-related gene expression (e.g.Sgk1) in OPCs and oligodendrocytes, and promoted OPC differentiation toward myelinating state. In the chronic phase, a subset of oligodendrocytes adopted a reactive-like phenotype characterized by elevated expression ofMaml2, Vcan, Sv2c, andCd63. Pseudo-time analysis revealed distinct functional states along the OPC-to-oligodendrocyte continuum, including self-renewal, migration, and differentiation. Cell-cell communication analysis identified the prosaposin- pleiotrophin axis as a dominant signaling pathway among oligodendrocyte lineage cells, and uncovered temporally restricted neuregulin ErbB signaling at the subacute stage.Significance. These findings reveal that oligodendrocyte lineage cells exhibit stage-dependent functional remodeling in response to electrode implantation-induced neuroinflammation, and highlight their potential as cellular targets for improving the long-term stability and performance of implantable neural electrodes.