Deafness due to exposure to excess noise, ototoxic drugs, or as a natural consequence of aging, results in-malleable changes in the central auditory system. Studies of the IC and auditory cortex provide the most evidence for functional changes with deafness. However, there is also some evidence for deafness related changes in the superior olivary complex (SOC) including changes in neurotransmitter levels and binding. Preliminary data collected prior to this application, indicate significant changes in mRNA for GAD 65, 67 and the GABA alpha 1 receptor in the inferior colliculus (IC). These data are consistent with reports of age and noise related changes and reports of a role for GABA in functional changes. Interestingly, one of the greatest differences observed from preliminary data following deafening was in the neuropeptide somatostatin which has not been previously reported to play a role in deafness related plasticity. Therefore the goal of the proposed experiments is to identify and examine neurotransmission related genes within two regions of the central auditory system (IC, and SOC) before and after deafening with aminoglycosides. Deafness related changes in somatostatin production in the IC will be assessed with Western blots while in situ hybridization and immunocytochemisty will be used to determine regional and cell specificity. Using relatively new gene array technology, the final experiments will test the deafness related differential gene expression within the SOC and compare those changes with differential gene expression within the IC. Finally, by comparing gene expression at different time points following deafness the studies also will address the transience and permanence of the changes observed. Little is known regarding the effects of deafening on the adult central auditory system even with the widespread use of cochlear implants and other prosthetic devices. The proposed studies will lead to an understanding of how the central auditory system is modulated by deafness and will therefore aid in the development of prosthetic devices designed to facilitate the re-introduction of hearing in hearing impaired individuals.
| Holt, Avril Genene; Asako, Mikiya; Lomax, Catherine A et al. (2005) Deafness-related plasticity in the inferior colliculus: gene expression profiling following removal of peripheral activity. J Neurochem 93:1069-86 |
