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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Clinical Investigator Award (CIA) (K08)
Project #
1K08DC006227-01A1
Application #
6774556
Study Section
Special Emphasis Panel (ZDC1-SRB-A (36))
Program Officer
Sklare, Dan
Project Start
2004-04-01
Project End
2009-03-31
Budget Start
2004-04-01
Budget End
2005-03-31
Support Year
1
Fiscal Year
2004
Total Cost
$200,853
Indirect Cost
Name
Medical College of Wisconsin
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
937639060
City
Milwaukee
State
WI
Country
United States
Zip Code
53226
Friedland, David R; Eernisse, Rebecca; Erbe, Christy et al. (2009) Cholesteatoma growth and proliferation: posttranscriptional regulation by microRNA-21. Otol Neurotol 30:998-1005
Friedland, David R; Eernisse, Rebecca; Popper, Paul (2008) Identification of a novel Vamp1 splice variant in the cochlear nucleus. Hear Res 243:105-12
Friedland, David R; Eernisse, Rebecca; Popper, Paul (2007) Potassium channel gene expression in the rat cochlear nucleus. Hear Res 228:31-43
Friedland, David R (2006) Structure and function in the auditory system: From cochlea to cortex. Anat Rec A Discov Mol Cell Evol Biol 288:326-30
Friedland, D R; Popper, P; Eernisse, R et al. (2006) Differentially expressed genes in the rat cochlear nucleus. Neuroscience 142:753-68
Friedland, David R; Popper, Paul; Eernisse, Rebecca et al. (2006) Differential expression of cytoskeletal genes in the cochlear nucleus. Anat Rec A Discov Mol Cell Evol Biol 288:447-65