Influence of heterogeneous myelination patterns on axonal conduction and vulnerability to demyelination

Abstract

AbstractAxons of the mammalian brain display significant variations in their myelination motifs. Far from being regular and uniform, the distribution patterns of myelin sheaths vary significantly between axons, and across brain areas. To explore the influence of such variability on axonal conduction, we developed an axon model exhibiting myelin distributions mirroring those observed experimentally in different regions of the central nervous system of mice. We also examined how varying myelination patterns predispose axons to failure. Our study shows such variability significantly impacts axonal conduction timing and reliability. Action potential propagation was found to be highly sensitive to the specific arrangement and ordering of myelinated and/or exposed segments along axons, indicating that axonal conduction is non-linear and path-dependent. Furthermore, properties of axonal conduction were found to differ between cortical and callosal axons, influencing their vulnerability to demyelination, while shaping both conduction time and predisposition to failure. Our analysis indicates that callosal axons are particularly sensitive to myelin changes, especially after damage. These findings highlight the crucial role of myelination profiles in brain function and disease.