Vestibular nerve regeneration in the bullfrog, Rana catesbeiana: Peripheral dendrites☆☆☆★★★

Abstract

Three experiments were conducted on healthy adult bullfrogs (Rana catesbeiana) for the purpose of investigating three characteristics of centrifugal vestibular afferent regeneration after complete transection of the anterior division of the vestibular nerve (AVN). In experiment 1 total fiber count and axon diameter measurements were obtained from the anterior canal nerve at three different time periods and compared with 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 282 +/- 23. The intermediate (4 to 6 weeks, n = 3) and late (8 to 16 weeks, n = 3) groups exhibited total fiber counts of 907 +/- 29 and 946 +/- 50, respectively, which were not different from normal (Mann-Whitney U, p > 0.2). Evaluation of fiber diameter distribution of the intermediate and late regenerated nerves revealed a reduction in axon diameter caliber compared with normal (analysis of variance, p < 0.0001). Thus transection of the AVN results in regeneration of all afferents that exhibit a reduction in axon diameter. In experiment 2 fibers innervating the anterior canal crista (ACC) were prelabeled before nerve transection. 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 observed innervating all three denervated vestibular receptors. This result demonstrated that reinnervation of the peripheral vestibular end organs after AVN transection is a nonspecific process. In experiment 3, 167 regenerated canal afferents were evaluated for functional recovery 16 weeks after transection. Both spontaneous and rotation-induced discharge characteristics were obtained and compared with those obtained from a sample of 254 normal afferents in a previous study (Hoffman LF. Factors affecting the response dynamics of canalicular primary afferent neurons in the bullfrog. St. Petersburg (FL): Association for Research in Otolaryngology; 1989). The mean spontaneous discharge coefficient of variation (CV) +/- standard deviation was 0.60 +/- 0.32 and 0.49 +/- 0.33 for ACC and HCC regenerated afferents, respectively, which did 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 0.05 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 regenerated ACC and HCC afferents, respectively, which were not different from the normal means of -33.77 +/- 24.31 degrees and -58.0 +/- 23.3 degrees (Mann-Whitney U). Furthermore, regenerated afferents exhibited a positive association between phase and CV, which was also true for normal afferents (correlation analysis, p > 0.001). Althoug...

The Frog Vestibular System as a Model for Lesion-Induced Plasticity: Basic Neural Principles and Implications for Posture Control

“…This plasticity phenomenon is common in amphibians (Sperry, 1945; Hernandez et al, 1998; Goto et al, 2002) and birds (Haque et al, 2008) but apparently absent in mammals. In frog, regeneration of vestibular afferents and reinnervation occurs both within the sensory epithelium after a nerve section distal to Scarpa’s ganglion (Figure 4B; Hernandez et al, 1998) as well as centrally in the vestibular nuclei after a nerve section between the ganglion and the brainstem (Newman and Honrubia, 1992).…”

“…This plasticity phenomenon is common in amphibians (Sperry, 1945; Hernandez et al, 1998; Goto et al, 2002) and birds (Haque et al, 2008) but apparently absent in mammals. In frog, regeneration of vestibular afferents and reinnervation occurs both within the sensory epithelium after a nerve section distal to Scarpa’s ganglion (Figure 4B; Hernandez et al, 1998) as well as centrally in the vestibular nuclei after a nerve section between the ganglion and the brainstem (Newman and Honrubia, 1992). Independent of the site of nerve section, peripheral and central regenerating afferent fibers form appropriate projections and reinnervate adequate vestibular endorgans and central neurons in the vestibular nuclei, respectively (Newman et al, 1986, 1987; Hernandez et al, 1998).…”

“…In frog, regeneration of vestibular afferents and reinnervation occurs both within the sensory epithelium after a nerve section distal to Scarpa’s ganglion (Figure 4B; Hernandez et al, 1998) as well as centrally in the vestibular nuclei after a nerve section between the ganglion and the brainstem (Newman and Honrubia, 1992). Independent of the site of nerve section, peripheral and central regenerating afferent fibers form appropriate projections and reinnervate adequate vestibular endorgans and central neurons in the vestibular nuclei, respectively (Newman et al, 1986, 1987; Hernandez et al, 1998). The remarkable spatio-temporal precision of this process is best illustrated by the reappearance of head motion-driven activity in afferent fibers and vestibulo-motor responses with gains that are comparable to those of controls (Hernandez et al, 1998; Goto et al, 2002).…”

“…Independent of the site of nerve section, peripheral and central regenerating afferent fibers form appropriate projections and reinnervate adequate vestibular endorgans and central neurons in the vestibular nuclei, respectively (Newman et al, 1986, 1987; Hernandez et al, 1998). The remarkable spatio-temporal precision of this process is best illustrated by the reappearance of head motion-driven activity in afferent fibers and vestibulo-motor responses with gains that are comparable to those of controls (Hernandez et al, 1998; Goto et al, 2002). With the exception of particular organizational differences in afferent fiber diameters and reinnervation patterns of hair cells in different areas of the sensory epithelium by thin and thick fibers, this plasticity mechanism is specific and results in a complete functional recovery of vestibular function if the sensory periphery remains preserved after the lesion.…”

“…With the exception of particular organizational differences in afferent fiber diameters and reinnervation patterns of hair cells in different areas of the sensory epithelium by thin and thick fibers, this plasticity mechanism is specific and results in a complete functional recovery of vestibular function if the sensory periphery remains preserved after the lesion. In fact, the persisting intact receptor epithelium exerts a presynaptic influence on the physiological characteristics of regenerating and reconnecting axons, thereby ensuring a certain spatio-temporal precision (Hernandez et al, 1998). This mechanism, however, appears to be specific to non-mammalian species and thus has only limited implications for explaining “vestibular compensation” in mammals.…”