Myelin sheaths are composed of spirally wrapped oligodendrocyte plasma membrane tightly compacted by a family of myelin-associated proteins that protect and insolate axonal fibers in neurons. They increase the transverse resistance of each fibre and lead to voltage-gated Na channel clustering at nodes of Ranvier supporting node-to-node saltatory conduction, which vastly accelerates conduction rates and limits repolarization energy requirements to the nodal domain. Adult myelin is adaptive with a rapidly growing evidence suggesting that such plasticity plays a key role in both normal and abnormal nervous system function. Insight into the mechanism through which such myelin changes are mediated remains limited. We have recently used computational techniques, image analysis and modeling approaches to quantify the relation between the different parameters defining the anatomy of axonal fibers in gene- edited mice and to explore how they affect their functional properties. Using the same approaches, we also investigated calcium dynamics in cultured oligodendrocyte precursor cells (OPCs) to determine the role of various ion channels and receptors in producing spontaneous local calcium transients (SCaLTs) known to play fundamental role in myelination. In this talk, I will provide an overview of the results obtained focusing on three key aspects: myelin-sheath plasticity in vivo, signal conduction along axons and SCaLT generation in OPCs.