Topography of Auditory Nerve Projections to the Cochlear Nucleus in Cats after Neonatal Deafness and Electrical Stimulation by a Cochlear Implant

Abstract

We previously reported that auditory nerve projections from the cochlear spiral ganglion (SG) to the cochlear nucleus (CN) exhibit clear cochleotopic organization in adult cats deafened as neonates before hearing onset. However, the topographic specificity of these CN projections in deafened animals is proportionately broader than normal (less precise relative to the CN frequency gradient). This study examined SG-to-CN projections in adult cats that were deafened as neonates and received a unilateral cochlear implant at ∼7 weeks of age. Following several months of electrical stimulation, SG projections from the stimulated cochleae were compared to projections from contralateral, non-implanted ears. The fundamental organization of SG projections into frequency band laminae was clearly evident, and discrete projections were always observed following double SG injections in deafened cochleae, despite severe auditory deprivation and/or broad electrical activation of the SG. However, when normalized for the smaller CN size after deafness, AVCN, PVCN, and DCN projections on the stimulated side were broader by 32%, 34%, and 53%, respectively, than projections in normal animals (although absolute projection widths were comparable to normal). Further, there was no significant difference between projections from stimulated and contralateral non-implanted cochleae. These findings suggest that early normal auditory experience may be essential for normal development and/or maintenance of the topographic precision of SG-to-CN projections. After early deafness, the CN is smaller than normal, the topographic distribution of these neural projections that underlie frequency resolution in the central auditory system is proportionately broader, and projections from adjacent SG sectors are more overlapping. Several months of stimulation by a cochlear implant (beginning at ∼7 weeks of age) did not lessen or exacerbate these degenerative changes observed in adulthood. One clinical implication of these findings is that congenitally deaf cochlear implant recipients may have central auditory system alterations that limit their ability to achieve spectral selectivity equivalent to postlingually deafened subjects.

Behavioral training restores temporal processing in auditory cortex of long-deaf cats

“…Surprisingly, despite the significantly shorter deafness durations and higher SGC survival, training-induced enhancements in temporal following ability in these animals remained significantly below that of behaviorally trained long-deaf animals [LDS(ϩ) group]. These findings underscore that the potent efficacy of training-induced temporal plasticity is not limited by long-term deafness and its deleterious effects on peripheral (e.g., Leake and Hradek 1988;Vollmer et al 2007) and central morpholog (e.g., Leake et al 2008;Lustig et al 1994;Nishiyama et al 2000).…”

Effects of Brain-Derived Neurotrophic Factor (BDNF) and Electrical Stimulation on Survival and Function of Cochlear Spiral Ganglion Neurons in Deafened, Developing Cats

“…Alteration in the SG neuronal membrane properties or channels also could account for the observed EABR threshold reductions. Alternatively, it should also be noted that previous animal studies have shown that lower EABR thresholds are correlated with better SG survival in the cochlear region near the stimulating electrodes (Leake et al 2008b). Thus, it may be possible that some neurons initially unresponsive to electrical stimulation, due to ototoxic drug administration effects, become viable and responsive during BDNF treatment.…”

“…Electrical stimulation from a CI has also been shown to promote SG survival in vivo in deafened adult guinea pigs (Hartshorn et al 1991;Kanzaki et al 2002;Lousteau 1987;Miller 2001;Miller and Altschuler 1995;Mitchell et al 1997) and in cats deafened early in life (Leake et al 1999(Leake et al , 2007(Leake et al , 2008b). In our laboratory, studies of cats deafened prior to hearing onset have shown that multichannel CI electrical stimulation applied over several months results in substantial improvement in SG neural survival (Leake et al 1999(Leake et al , 2007(Leake et al , 2008a above that seen in the contralateral deafened cochleae. Other studies, however, have not found evidence of trophic effects of electrical stimulation (Araki et al 1998;Coco et al 2007;Li et al 1999;Shepherd et al 1994).…”

“…These disparities in findings suggest that differences among animal models, methods of stimulation (e.g., the position of stimulating electrodes, applied signals, and efficacy in exciting neurons across a broad sector of the spiral ganglion), and/or methods of analysis of SG density are critically important. But even in studies showing highly significant trophic effects, electrical stimulation only partly prevents SG degeneration after deafness (Leake et al 2008b). Thus, there has been considerable recent interest in neurotrophic agents that might be used in conjunction with cochlear implantation to enhance SG and auditory nerve survival (see Staecker et al 2010).…”

Effects of brain-derived neurotrophic factor (BDNF) on the cochlear nucleus in cats deafened as neonates

“…Digital images of sections were captured using a Zeiss Axioskop 2, a 2.5× objective and a Zeiss AxioCam MRc5 digital camera. Cytoarchitectural criteria according to Kiang et al, (1975); Leake et al, (2002); Leake et al,(2008); Stakhovskaya et al, (2008) were utilized to outline the three individual CN subdivisions in each imaged section (excluding the cochlear nerve root). The boundary between the DCN and the PVCN was defined by the intermediate acoustic stria in caudal sections and using the granule cell layer as a landmark in more rostral sections.…”