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.
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