Cortical neurons exhibit diverse myelination patterns that scale between mouse brain regions and regenerate after demyelination

Cody L Call,Dwight E Bergles

doi:10.1038/s41467-021-25035-2

Cody L Call, Dwight E Bergles

Open Access

https://doi.org/10.1038/s41467-021-25035-2

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Abstract

ABSTRACTAxons in the cerebral cortex show a broad range of myelin coverage. Oligodendrocytes establish this pattern by selecting a cohort of axons for myelination; however, the distribution of myelin on distinct neurons and extent of internode replacement after demyelination remain to be defined. Here we show that myelination patterns of seven distinct neuron subtypes in somatosensory cortex are influenced by both axon diameter and neuronal identity. Preference for myelination of parvalbumin interneurons was preserved between cortical areas with varying myelin density, suggesting that regional differences in myelin abundance arises through local control of oligodendrogenesis. By imaging loss and regeneration of myelin sheaths in vivo we show that myelin distribution on individual axons was altered but overall myelin content on distinct neuron subtypes was restored. Our findings suggest that local changes in myelination are tolerated, allowing regenerated oligodendrocytes to restore myelin content on distinct neurons through opportunistic selection of axons.

Highlights

Axons in the cerebral cortex show a broad range of myelin coverage
PV and SOM neurons tended to have shorter unmyelinated segments, there were no statistically significant differences between the distributions (p = 0.095, Kruskal–Wallis one-way ANOVA). These studies reveal that different neurons that extend axons within layer I of the adult somatosensory cortex exhibit distinct, highly variable myelination patterns
0.8 μm [0.11, 0.89] (NXPH4) (Fig. 4e). These results indicate that myelination of cortical axons does not follow a strict diameter–myelination relationship similar to that described in the PNS12–14, and that other neuron intrinsic factors profoundly influence the probability of being selected for myelination

Summary

Introduction

Axons in the cerebral cortex show a broad range of myelin coverage. Oligodendrocytes establish this pattern by selecting a cohort of axons for myelination; the distribution of myelin on distinct neurons and extent of internode replacement after demyelination remain to be defined. We used a combination of cell-specific axon labeling with high-resolution imaging of myelin sheaths to define the myelination patterns of seven distinct excitatory and inhibitory neuronal subtypes that extend axon collaterals within layer I of the somatosensory cortex. By performing longitudinal time-lapse imaging of local PV interneurons and thalamocortical VM neurons we found that the precise pattern of myelin along individual axons was altered following regeneration, at the population level, the total myelin content on these distinct neuronal subtypes was preserved. These findings suggest that regeneration of oligodendrocytes relies on opportunistic target selection to restore the content of myelin on diverse neuronal subtypes in the mammalian cortex

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