Differential Gene Expression in the Cochlear Nucleus

Medical College Of Wisconsin, Milwaukee WI

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Abstract

DESCRIPTION (provided by applicant): Approximately a half million Americans are severely deafened and 1 in 3 individuals over 65 demonstrates significant hearing loss. Rehabilitative options have improved in the ability to restore hearing levels however problems with discrimination, hearing in noise and tinnitus remain. Recent studies indicate that the central auditory system plays a significant role in these problems, however, precise anatomic and physiological correlation is lacking. We propose to define a genetic model of central auditory function to better understand normal and pathologic auditory processes. The fundamental hypothesis of this application is that the specialized anatomic and physiologic properties of the cochlear nucleus are reflected in the genes expressed by its neurons (i.e., the transcriptome). This study will use serial analysis of gene expression (SAGE) to characterize and quantify mRNA expressed within cochlear nucleus subdivisions and neurons. Modern bioinformatics techniques will be applied to identify unique, differentially expressed and novel genes in this auditory brain stem region. These genes will be localized to specific classes of cells and cochlear nucleus subdivisions by in situ hybridization and immuno-histochemistry. Similar genetic and localizing studies will also be performed on the multipolar class of cochlear nucleus neurons. These experiments will enable the correlation of physiologic and morphologic properties of the auditory system with specific genetic transcripts. The generation of a molecular profile of the cochlear nuclei will provide greater insight into the auditory system by demonstrating the fundamental mechanisms subserving signal processing. These data will also provide a powerful template upon which to test and design novel treatments for improving hearing, discrimination and tinnitus in a significant portion of the population.