A ROLE FOR OLIGODENDROCYTES IN THE STABILIZATION OF OPTIC AXON NUMBERS

Differentiated oligodendrocytes express neurite growth inhibitory prot eins at a time when these cells are involved in the myelination of rec ently formed fiber pathways. As the process of myelination follows the completion of neurite outgrowth and is concurrent with the stabilizat ion of fiber numbers in a pathway, we set out to determine whether mye lination and fiber tract stability could be causally related. Myelin f ormation was prevented in the rat retinofugal pathway by x-irradiating the optic nerves during oligodendrocyte proliferation. Electron micro scopic and immunohistochemical analysis of irradiated optic nerves at P15 showed that oligodendrocytes and myelin were virtually absent. Opt ic fiber numbers were determined at 2 weeks of age throughout the leng th of normal and x-irradiated nerves. In some cases, normal or irradia tion-treated pups were intraocularly injected with FGF 5 d prior to th e fiber count in order to promote neurite outgrowth. Axon counts showe d that the total fiber number in a myelin-free optic nerve was 10-30% higher than that of a myelinated nerve. Further, fiber numbers fluctua ted by as much as 20% along the length of a myelin-free nerve but were relatively constant throughout the length of a myelinated nerve. Trea tment of myelinated nerves with fibroblast growth factor (FGF) had no effect on either total fiber numbers or fiber number fluctuation. Conv ersely, fiber numbers in myelin-free/FGF-treated optic nerves were as much as 40% higher than in normals. Furthermore, total fiber numbers a long the length of these nerves fluctuated by up to 34%. These results indicate that, in the absence of myelination, optic fibers are able t o form sprouts. This suggests that oligodendrocytes have a role in pre venting sprouting and stabilizing the number of fibers in a pathway du ring development.