Although a great deal is known about the nonlinear characteristics of the peripheral auditory systems of adult vertebrates, very little is known about their development. Results from recent experiments indicate that transduction dynamics are linear during the early stages of mammalian development and that the acquisition of adultlike characteristics occurs rapidly for simple forms of stimulation (i.e., tonal stimuli), coinciding with the final stages of cochlear differentiation. Cochlear nonlinearities, on the other hand, in addition to appearing later in postnatal life, require longer to mature than do more simple response features. We hypothesize that nonlinear response properties of the peripheral auditory system arise near the end of the first postnatal week, and that their mechanism(s) of action is independent of frequency, as indicated by the simultaneous developmental appearance of two-tone suppression above and below the characteristic frequency of auditory nerve fibers spanning the audiometric range. We also hypothesize that two-tone suppression and intermodulation distortion products develop in concert with other cochlear phenomena, like tuning, and propose to use converging methods (i.e., Fourier analysis of individual auditory nerve fiber responses and distortion product otoacoustic emissions) to identify commonalities linking otherwise disparate nonlinear phenomena. Very little is known about the development of level-dependent relationships among cochlear distortion products and we hypothesize that they are complex, reflecting the developmental acquisition of dynamic frequency and level properties of peripheral auditory function in general. Distortion product otoacoustic emissions will be employed to accomplish objectives associated with this aspect of proposed research. We also hypothesize that auditory function is more susceptible to energy-depleting and/or blocking actions early in development and plan to experimentally manipulate energy-dependent cochlear processes at various stages of development, through the agencies of systemic furosemide administration and hypoxia. These agents disrupt active cochlear mechanics, and the purpose of proposed experiments is the identification of age-dependent differences revealed by the actions of these manipulations. Ultimately, the purpose of the proposed research is to extend our understanding of the role of peripheral auditory nonlinearities in cochlear processing in adults and immature mammals, as well as to form a basis for future research targeting clinical issues related to congenital deafness, and the consequences of exposure to environmental hazards during critical developmental periods.

Project Start
1999-09-01
Project End
2001-08-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
10
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Father Flanagan's Boys' Home
Department
Type
DUNS #
City
Boys Town
State
NE
Country
United States
Zip Code
68010
Song, Lei; McGee, Joann; Walsh, Edward J (2008) The influence of thyroid hormone deficiency on the development of cochlear nonlinearities. J Assoc Res Otolaryngol 9:464-76
Song, Lei; McGee, JoAnn; Walsh, Edward J (2008) Development of cochlear amplification, frequency tuning, and two-tone suppression in the mouse. J Neurophysiol 99:344-55
Varga, R; Avenarius, M R; Kelley, P M et al. (2006) OTOF mutations revealed by genetic analysis of hearing loss families including a potential temperature sensitive auditory neuropathy allele. J Med Genet 43:576-81
Song, Lei; McGee, Jo Ann; Walsh, Edward J (2006) Consequences of combined maternal, fetal and persistent postnatal hypothyroidism on the development of auditory function in Tshrhyt mutant mice. Brain Res 1101:59-72
Song, Lei; McGee, Joann; Walsh, Edward J (2006) Frequency- and level-dependent changes in auditory brainstem responses (ABRS) in developing mice. J Acoust Soc Am 119:2242-57
Higgins, Maureen B; McCleary, Elizabeth A; Ide-Helvie, Dana L et al. (2005) Speech and voice physiology of children who are hard of hearing. Ear Hear 26:546-58
Pennings, Ronald J E; Topsakal, Vedat; Astuto, Lisa et al. (2004) Variable clinical features in patients with CDH23 mutations (USH1D-DFNB12). Otol Neurotol 25:699-706
Varga, R; Kelley, P M; Keats, B J et al. (2003) Non-syndromic recessive auditory neuropathy is the result of mutations in the otoferlin (OTOF) gene. J Med Genet 40:45-50
Higgins, Maureen B; McCleary, Elizabeth A; Carney, Arlene Earley et al. (2003) Longitudinal changes in children's speech and voice physiology after cochlear implantation. Ear Hear 24:48-70
Bhattacharya, Gautam; Miller, Caroline; Kimberling, William J et al. (2002) Localization and expression of usherin: a novel basement membrane protein defective in people with Usher's syndrome type IIa. Hear Res 163:1-11

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