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

Abstract

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.

Brainstem inputs to the ferret medial geniculate nucleus and the effect of early deafferentation on novel retinal projections to the auditory thalamus

“…One possible explanation for this find- ing is that injured axons were able to regenerate and grow around the injury site by following the course of axons spared by the damage. Consistent with this hypothesis, regeneration of optic, olfactory and pyramidal tract axons after early injury, has been shown to occur in the hamster and rat (Devor, 1975(Devor, , 1976Kalil and Reh, 1979;Bernstein and Stelzner, 1981;So et al, 1981;Grafe, 1983). An alternative explanation is that new routes to the MGN were established by ingrowing axons that had not yet reached the MGN at the time of lesion.…”

Chronotopic organization of olfactory bulb axons in the lateral olfactory tract

“…This type of projection has been described and suggested to innervate the medial part of the tubercle (Devor, 1976). The tubercle is the olfactory target area that receives the latest innervation by OB axons (Schwob and Price, 1984), and it receives a heavier projection from tufted cells (Haberly and Price, 1977;Skeen and Hall, 1977;Scott, 1981;Grafe and Leonard, 1982), the late-born projection neurons of the OB (Hinds, 1968;Bayer, 1983;Grafe, 1983). These facts suggest that c-kit expression marks the selective projection over the tubercle at late stages, because these axons are projected from late-born neurons in the OB.…”

“…8A). The later injections of BrdU preferentially labeled tufted cells, the late-born projection neurons (Hinds, 1968;Bayer, 1983;Grafe, 1983), when examined in the postnatal OB. In conclusion, these results argue that c-kit is transiently expressed by newborn projection neurons in the OB that are radially migrating from the ventricular zone toward their destinations.…”

Elevated expression of B‐50 (GAP‐43)‐mRNA in a subpopulation of olfactory bulb mitral cells following axotomy

“…In neonatal rodents the LOT has a considerable regenerative capacity (Devor, 1976). Following a transection of the LOT during the first week of life, mitral cell axons penetrate the lesion and reinnervate caudal target areas, resulting in neuroanatomical and behavioral recovery (Grafe, 1983;Small and Leonard, 1983). In adult animals, however, the regenerative ability of axons across a LOT lesion is significantly diminished, concomitant with extensive glia scar formation (Sijbesma and Leonard, 1986).…”