Developmental factors affecting regeneration in the central nervous system: early but not late formed mitral cells reinnervate olfactory cortex after neonatal tract section.

If the lateral olfactory tract (LOT) of the golden hamster is transected in the first week of postnatal life, axons will grow back through the cut and reinnervate the terminal regions. Functional recovery occurs only when the terminal regions are reinnervated. The experiments reported here tested the hypothesis that reinnervation is due to neogenesis: the continued growth of newly formed axons which were not severed by the lesion. In the first experiment the birth dates of the mitral and tufted cells were determined in the hamster. It was found that mitral cells are formed on gestational days 11 and 12 (E11 and E12) and tufted cells on E11 to E14. Experiment 2 involved the combination of [3H]thymidine labeling, for the time of cell formation, with the retrograde transport of horseradish peroxidase (HRP), at a time when the LOT projections are not yet complete. The axons of early formed cells were found to reach the olfactory cortex before those of later formed cells. Experiment 3 examined the possibility that the axons which grow through an early LOT transection are new axons that had not yet reached the level of the cut. Animals were given [3H]thymidine to label the times of formation of mitral and tufted cells and then were given a transection of the LOT on postnatal day 3 (P3). After a recovery period sufficient to allow axonal regrowth and reinnervation, HRP was placed in the olfactory projection region caudal to the prior LOT section. The original hypothesis was not supported. Cells that are formed early and send out their axons early are able to reinnervate the olfactory cortex, whereas late formed cells do not. The results of this experiment suggest that the factors which prevent the regrowth of axons when the LOT is cut after P7 may depend on the stage of development of the tissue into which the axons are growing, rather than in the cells of origin and their axons.