A computational study of the impact of inhomogeneous internodal lengths on conduction velocity in myelinated neurons

Age-related decreases in the conduction velocity (CV) of action potentials along myelinated axons have been linked to morphological changes in the myelin sheath. In particular, evidence suggests the presence of segmental demyelination and remyelination of axons. In remyelinated segments, the distance between adjacent nodes of Ranvier is typically shorter, and myelin sheaths are thinner. Both experimental and computational evidence indicates that shortened internodes slows CV. In this computational study, we determine the impact of progressive segmental demyelination and remyelination, modeled by shorter internodes with thinner myelin sheaths interspersed with normal ones, upon the CV. We find that CV progressively decreases as the number of remyelinated segments increases, but this decrease is greater than one would expect from an estimate of the CV based merely upon the number of short and long internodes. We trace the additional suppression of the CV to transitions between long and short internodes. Our study presents an important consideration for the precise modeling of neural circuits with remyelinated neurons.