Refinement of axonal conduction and myelination in the mouse optic nerve indicate an extended period of postnatal developmental plasticity

Abstract

Retinal ganglion cells generate a pattern of action potentials to communicate visual information from the retina to cortical areas. Myelin, an insulating sheath, wraps axonal segments to facilitate signal propagation and when deficient, can impair visual function. Optic nerve development and initial myelination has largely been considered completed by the fifth postnatal week. However, the relationship between the extent of myelination and axonal signaling in the maturing optic nerve is not well characterized. Here, we examine the relationship between axon conduction and elements of myelination using extracellular nerve recordings, immunohistochemistry, western blot analysis, scanning electron microscopy, and simulations of nerve responses. Comparing compound action potentials from mice aged 4–12 weeks revealed five functional distinct axonal populations, an increase in the number of functional axons, and shifts toward fast-conducting axon populations at 5 and 8 weeks postnatal. At these ages, our analysis revealed increased myelin thickness, lower g-ratios and changes in the 14 kDa MBP isoform, while the density of axons and nodes of Ranvier remained constant. At 5 postnatal weeks, axon diameter increased, while at 8 weeks, increased expression of a mature sodium ion channel subtype, Na_v 1.6, was observed at nodes of Ranvier. A simulation model of nerve conduction suggests that ion channel subtype, axon diameter, and myelin thickness are more likely to be key regulators of nerve function than g-ratio. Such refinement of axonal function and myelin rearrangement identified an extended period of maturation in the normal optic nerve that may facilitate the development of visual signaling patterns.