Effects of age at onset of deafness and electrical stimulation on the developing cochlear nucleus in cats

Abstract

This study examined the effects of deafness and intracochlear electrical stimulation on the anatomy of the cochlear nucleus (CN) after a brief period of normal auditory development early in life. Kittens were deafened by systemic ototoxic drug injections either as neonates or starting at postnatal day 30. Total CN volume, individual CN subdivision volumes, and cross-sectional areas of spherical cell somata in the anteroventral CN (AVCN) were compared in neonatally deafened and 30-day deafened groups at 8 weeks of age and in young adults after approximately 6 months of electrical stimulation initiated at 8 weeks of age. Both neonatal and early acquired hearing loss resulted in a reduction in CN volume as compared to normal hearing cats. Comparison of 8- and 32-week old groups indicated that the CN continued to grow in both deafened groups despite the absence of auditory input. Preserving normal auditory input for 30 days resulted in a significant increase in both total CN volume and cross-sectional areas of spherical cell somata, as compared to neonatally deafened animals. Restoring auditory input in these developing animals by unilateral intracochlear electrical stimulation did not elicit any difference in CN volume between the two sides, but resulted in 7% larger spherical cell size on the stimulated side. Overall, the brief period of normal auditory development and subsequent electrical stimulation maintained CN volume at 80% of normal and spherical cell size at 86% of normal ipsilateral to the implant as compared to 67% and 74%, respectively, in the neonatally deafened group.

Figure 1

Coronal sections through the cochlear nucleus taken just posterior to the auditory nerve root are shown from a neonatally deafened animal (left), a 30-day deafened animal (center) and a normal hearing animal (right) examined at 8 weeks of age. Dashed lines illustrate tracings of the perimeter of the CN and its individual subdivisions used to determine cross-sectional areas and volume. (DCN, dorsal cochlear nucleus; PVCN, posteroventral cochlear nucleus.)

Figure 2

Mean total CN volumes are shown for all experimental groups. Significant group effects of both the onset (p<0.001) and duration of deafness (p<0.001) on CN development were observed in young animals (two-way ANOVA). The 30-day deafened groups exhibited significantly larger CN volumes than the neonatally deafened groups, both at 8 weeks and 8 months of age (post-hoc comparisons, Tukey test). In turn, normal CN volume was significantly larger than the 30-day deafened and neonatally deafened groups at both ages (asterisks). There was a significant difference in total CN volume (p<0.001) between the 8 week and 8 month old animals in both of the deafened groups, as well as in the normal group. Error bars represent standard error of the mean.

Figure 3

Mean cross-sectional areas of AVCN spherical cell somata in neonatally deafened, 30-day deafened and normal animals studied at 8 weeks and 8 months of age. Data for the deafened groups at 8 months of age are from the CN on the non-implanted side only. Significant group effects of the onset of deafness (p<0.001) and duration of deafness (p=0.013) on spherical cell size were observed (two-way ANOVA, significant interaction, p=0.027). In the animals studied at 8 weeks of age, cell area in the 30-day deafened group had a tendency to be larger than in the neonatally deafened group, but did not achieve a statistically significant difference from either the neonatally deafened or normal groups in post-hoc multiple comparisons (Tukey test). At 8 months of age, a significant difference in spherical cell size between the 30-day deafened and neonatally deafened groups (data from CN on non-implanted side) was observed (p=0.028), and cells in both groups were significantly smaller than normal (p<0.001). Neither of the deafened groups of animals studied at 8 months of age showed a significant increase in the spherical cell size as compared to the younger (8 week old) animals. In contrast, normal animals exhibited significant growth during this same period, with an increase in mean soma area of about 17% of normal. Asterisks indicate groups that were significantly different from normal animals. Error bars represent standard error of the mean.

Figure 4

Mean cross-sectional areas of the AVCN spherical cells were significantly larger in the CN ipsilateral to the cochlear implant in both neonatally and 30-day deafened groups (p<0.001, two-way repeated measures ANOVA with stimulation and onset of deafness as factors, no significant interaction). Error bars represent standard deviations.