Regenerative Capacity of Bulbar Projection Neurons During Development: A Quantitative Neuronal Analysis With Functional Correlation

Abstract

Critical periods and degrees of regeneration in injured olfactory bulbar projection neurons (mitral cells) were examined in adult rats whose lateral olfactory tracts (LOTs) were transected at different postnatal (P) days. After the LOTs were transected at P7, P10, and P14, a retrograde fluorescent tracer, Fluoro-Gold (FG), was injected into the posterior olfactory cortex (the olfactory tubercle and the piriform cortex), a target brain region of mitral cells, 5 weeks after the transection. FG (+) mitral cells were observed in P7 LOT-transected bulbs and some of P10 LOT-transected bulbs but not in P14 LOT-transected bulbs. Neuron numbers of regenerated FG (+) mitral cells in P2 LOT-transected adult rats decreased to approximately 70% of the normal values (actually counted number: 804±46; stereologically estimated number: 49 700±4300), and 100% of these rats were demonstrated to exhibit olfactory discriminative ability in our previous study. Meanwhile, the numbers in P7 LOT-transected adult rats further decreased to approximately 40% of the normal values, and 78% of these rats showed olfactory discriminative ability. We conclude that the critical periods of spontaneous regeneration of the LOT are between P0 and P10 and that the proportions of regenerated mitral cells decreased as rats became older.

Effect of graded nerve pressure injuries on motor function

“…In our previous study, we demonstrated that a functionally essential neuronal population exists for a specific neural function. 4,5,8,9,11,13,14,16 Similarly, concerning axonal components essential for normal motor function, approximately 40% of undamaged axons appear to be sufficient for normal motor function in rats with a common peroneal nerve-crush injury because the ratios of residual axons to acetylcholine receptors in the nervecrushed rats with normal motor function (SSI above -20) ranged from 36.5% to 88.7%, and the ratios for the success group in the slope-walking test at angles of 30° and 45° ranged from 14.7% to 88.7% and from 39.8% to 88.7%, respectively. However, for some nerve-injured rats, there were inconsistencies between motor function and the ratio of undamaged residual axons to acetylcholine receptors.…”

“…4,5,8,9,11,13,14,16 However, the number of nerve fibers required at the neuromuscular junction to maintain normal motor function is unknown. Therefore, the purpose of this study was to evaluate the extent to which undamaged residual axons contributed to motor function, and to determine the minimum number of nerve fibers required to maintain normal motor function after nerve injury.…”

Acetyl-l-carnitine enhances myelination of regenerated fibers of the lateral olfactory tract

“…We have recently reported regeneration of LOT in developing rats during the early suckling period [11,13], and such regeneration of LOT had critical periods early in life [13]. Interestingly, the regenerated olfactory system was functional 10 days [14] and 4…”

“…LOT transection was performed in P2 pups (n = 70) unilaterally on the left side, as described previously [11][12][13]. Briefly, the LOT was transected at the posterior half of the olfactory stria by inserting the tip of a knife (Ophthalmic Scleral MVR Knife, 25 gauge; Alcon, Tokyo, Japan) from the ventrolateral aspect of the head.…”

“…The lateral olfactory tract (LOT) is the main fiber tract of the central olfactory system and exclusively consists of myelinated axon fibers. We have recently demonstrated that the neonatally transected LOT can be replaced by newly-formed axon fibers connecting the olfactory bulb and the olfactory cortex (the olfactory tubercle and piriform cortex) via the transected site at a later stage [11][12][13][14]. Because the regenerated LOT is primarily composed of unmyelinated axon fibers, LOT injury is a good animal model to examine the effects of ALC on myelin formation in the developing brain.…”