Dynamic functional changes in white matter during development

The optic nerve is a pure white matter tract and in the adult, virtually all axons are myelinated. In the mouse optic nerve myelination begins around postnatal day 7 and continues until about 5 weeks of age. In this study, axonal conduction in the mouse optic nerve (aged 4-12 weeks) was measured using the Stys suction electrode method. Nerves were dissected behind the retina and at the optic chiasm prior to being inserted into stimulating and recording suction electrodes in an oxygenated artificial cerebrospinal fluid bath for extracellular recordings. Electrical stimulation induced axons to fire action potentials that were recorded as compound action potentials (CAP). The resultant CAP waveform can be used to provide a relative measure of the total number of responsive neurons and to distinguish axonal populations by speed of conduction. The total number of responsive axons steadily increased through development until 12 weeks of age, while the distribution of axon firing rates varied. In 4 week old mice, there were two distinct populations of responsive axons which may reflect unmyelinated and myelinated populations. In 5 and 6 week old mice, the distribution expanded to a wider range of conduction velocities, with the majority of axons conducting at intermediate speeds. This entire distribution shifted to become faster in 8 week old mice, with an increase in intermediate-speed axons. In 12 week old mice, the distribution shifted to predominantly favor faster speeds. This data suggests that the functional properties of the nerve are dynamic, favoring faster axon conduction during development. Given that morphological studies suggest myelination is largely complete by 5 weeks, the subsequent refinement of axonal conduction rates may reflect more effective myelination, changes in nodes of Ranvier or axonal maturation. Current studies are designed to distinguish between these possibilities