Myelin sheaths persist for weeks following axon degeneration

Axon degeneration underlies clinical deficits in traumatic injuries and neurodegenerative disease. It is not clear how myelinating oligodendrocytes are directly affected by or respond to axon injury and loss. Here, we combined intravital imaging with laser axotomy or single neuron ablation to determine the longitudinal responses by oligodendrocytes that myelinate the degenerating axon. We find that while axons rapidly degenerate, myelin sheaths devoid of axon can persist for weeks. These remaining myelin sheaths lose compaction and slowly shrink. Local to the injury, oligodendrocyte homeostasis is largely maintained, with only a brief change in myelin sheath structural plasticity. After neuron ablation and axotomy, clearance of axon debris is delayed if the axon is myelinated. However, longitudinal imaging of microglia revealed only rare microglial engagement with injured axons, regardless of myelination status. Likewise, microglia did not engage with de-axoned myelin sheaths. These findings highlight the stability of myelinating oligodendrocytes and provide insight into homeostatic neuroglia responses following injury.