Jd. Hernandez et al., VESTIBULAR NERVE REGENERATION IN THE BULLFROG, RANA-CATESBEIANA - PERIPHERAL DENDRITES, Otolaryngology and head and neck surgery, 119(3), 1998, pp. 244-254
Three experiments were conducted on healthy adult bullfrogs (Rana cate
sbeiana) for the purpose of investigating three characteristics of cen
trifugal vestibular afferent regeneration after complete transection o
f the anterior division of the vestibular nerve (AVN). In experiment 1
total fiber count and axon diameter measurements were obtained from t
he anterior canal nerve at three different time periods and compared w
ith normal. The normal group (n = 3) demonstrated a total fiber count
of 1001 +/- 76 (SEM). The early time period (1 to 2 weeks, n = 3) did
not completely regenerate as demonstrated by a total fiber count of 28
2 +/- 23. The intermediate (4 to 6 weeks, n = 3) and late (8 to 16 wee
ks, n = 3) groups exhibited total fiber counts of 907 +/- 29 and 946 /- 50, respectively, which were not different from normal (Mann-Whitne
y U, p > 0.2). Evaluation of fiber diameter distribution of the interm
ediate and late regenerated nerves revealed a reduction in axon diamet
er caliber compared with normal (analysis of variance, p < 0.0001). Th
us transection of the AVN results in regeneration of ail afferents tha
t exhibit a reduction in axon diameter. In experiment 2 fibers innerva
ting the anterior canal crista (ACC) were prelabeled before nerve tran
section. After the labeling procedure the AVN (n = 3) was sectioned at
a location that resulted in denervation of three vestibular receptors
: the ACC, horizontal canal cristae (HCC), and utricular macula. After
4 weeks of regeneration the ACC fibers that were prelabeled were obse
rved innervating all three denervated vestibular receptors. This resul
t demonstrated that reinnervation of the peripheral vestibular end org
ans after AVN transection is a nonspecific process. In experiment 3, 1
67 regenerated canal afferents were evaluated for functional recovery
16 weeks after transection. Both spontaneous and rotation-induced disc
harge characteristics were obtained and compared with those obtained f
rom a sample of 254 normal afferents in a previous study (Hoffman LF.
Factors affecting the response dynamics of canalicular primary afferen
t neurons in the bullfrog. St. Petersburg (FL): Association for Resear
ch in Otolaryngology; 1989). The mean spontaneous discharge coefficien
t of variation (CV) +/- standard deviation was 0.60 +/- 0.32 and 0.49
+/- 0.33 for ACC and HCC regenerated afferents, respectively, which di
d not differ from the normal means of 0.63 +/- 0.33 and 0.54 +/- 0.36
(Mann-Whitney, p > 0.2). Response gains and phases obtained during 0.0
5 Hz sinusoid rotations at 15 degrees/second maximum horizontal table
velocity also demonstrated normal discharge characteristics. The mean
phases were -28.2 +/- 25.2 degrees and -55.9 +/- 21.5 degrees for rege
nerated ACC and HCC afferents, respectively, which were not different
from the normal means of -33.77 +/- 24.31 degrees and -58.0 +/- 23.3 d
egrees (Mann-Whitney U). Furthermore, regenerated afferents exhibited
a positive association between phase and CV, which was also true for n
ormal afferents (correlation analysis, p 0.001). Although the mean gai
ns for regenerated ACC and HCC (7.13 +/- 5.5 and 3.3 +/- 2.4 spikes.se
c(-1)/degrees.sec(-2), respectively) afferents were reduced from norma
l ACC and HCC (14.8 +/- 12.52 and 7.76 +/- 6.58 spikes.sec(-1)/degrees
.sec(-2), respectively) afferents (Mann-Whitney U, p > 0.0001), a posi
tive association between gain and CV was also demonstrated by regenera
ted afferents, as was the case for normal afferents (correlation analy
sis, p < 0.001). Thus the overall response discharges of regenerated a
fferents were comparable with normal afferents. Normally, large fibers
innervate central regions of the receptor, and smaller fibers innerva
te the peripheral regions. However, the data from experiments 1 and 2
demonstrate that vestibular nerve regeneration results in a dissociati
on between the normal topographic organization of fiber size and regio
nal innervation of the receptor epithelium. Nonetheless, both spontane
ous and stimulus-induced discharge characteristics remain unaltered in
the regenerated condition. Because the presynaptic epithelial feature
s also remained unaltered after nerve transection, these data demonstr
ate the importance presynaptic factors in governing afferent discharge
characteristics.