Evidence for Myelin Sheath Remodeling in the CNS Revealed by In Vivo Imaging

The length of myelin sheaths affects conduction speed along axons and information propagation. It has recently become clear that myelin may be adaptively modified to modulate circuit function, implying that length remodeling of myelin sheaths should occur. However, direct evidence for such events is lacking. We have investigated how myelination patterns are formed, maintained, and remodeled using long-term imaging and myelin ablation in zebrafish. We demonstrate that length differences between myelin sheaths are established by rapid and variable growth within 3 days after their formation, independently of their time of formation, and even along discontinuously myelinated axons. Afterward, sheaths continue extending at similar rates to compensate for overall animal growth. In consequence, once axon myelination patterns are established, they are maintained over long periods of time. We tested whether mature myelin sheaths can remodel by removing individual sheaths from single axons by targeted ablation. Remarkably, extensive changes in sheath length and number occurred, which frequently restored the original myelination pattern. Our results show that axons can control myelin growth and remodeling, and we provide evidence for a homeostatic control of axon myelination patterns by maintenance and remodeling of myelin sheath length, with implications for circuit development, function, and repair

Clusters of neuronal neurofascin prefigure the position of a subset of nodes of Ranvier along individual central nervous system axons in vivo

The spacing of nodes of Ranvier crucially affects conduction properties along myelinated axons. It is assumed that node position is primarily driven by growing myelin sheaths. Here, we reveal an additional mechanism of node positioning that is driven by the axon. Through longitudinal live imaging of node formation dynamics in the zebrafish central nervous system, we show that stable clusters of the cell adhesion molecule neurofascin a can accumulate at specific sites along axons prior to myelination. While some of these clusters are pushed into future node position by extending myelin sheaths, others are not and thus prefigure the position of where a mature node forms. Animals that lack full-length neurofascin a show increased internodal distances and less regular nodal spacing along single axons. Together, our data reveal the existence of an axonal mechanism to position nodes of Ranvier that does not depend on regulation by myelin sheath growth

Functional implication for myelin regeneration in recovery from ischaemic stroke.

This scientific commentary refers to ‘Prolonged myelin deficits contribute to neuron loss and functional impairments after ischaemic stroke’ by Cheng et al. (https://doi.org/10.1093/brain/awae029)