Development of Cochlear Nonlinearities in Normal and Tshr Mutant Mice

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Song, Lei
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Aim - (from the introduction - no abstract provided) |The goal of this project is twofold. The primary goal is to improve our understanding of cochlear development, and the development of cochlear nonlinearity in particular. The secondary goal is to comprehensively characterize the physiological basis of hypothyroidism induced otopathology. To accomplish these goals, the development of auditory function was studied in both normal mice (BALB/c) and a strain commonly referred to as the hyt, or Tshr mouse. The Tshr mouse expresses a naturally occurring point mutation in the gene that encodes the thyrotropin receptor resulting in the loss of its ability to bind thyroid stimulating hormone, a condition that leads to thyroid gland hypoplasia and profound congenital hypothyroidism. The defect is transmitted as an autosomal recessive trait, so that affected individuals are homozygous for the trait (Tshrkyt/hyt). Physiological differences between normal and hypothyroid mice served as a platform upon which the analysis of transduction nonlinearity was investigated.|The primary tool used to assess general auditory function in this study was the auditory brainstem response (ABR). To assess nonlinear aspects of peripheral auditory function, a forward masking paradigm was used to generate ABR derived tuning curves. If one assumes that the tip of tuning curves represents the activity of a nonlinear element, or elements, of cochlear transduction, and that the tail portion of the curve is representative of passive transduction mechanics, the tip-to-tail ratio (the difference between tip and tail thresholds) can be taken as an estimate of the gain of cochlear amplification that occurs as a consequence of active, energy consuming transduction events. Likewise, two-tone suppression (TTS), another common, popular measure of transduction nonlinearity, was assessed by determining the degree to which responses were “released” from masking by the addition of a suppressor signal (see study 3 methods section for details).|Three basic issues were addressed in an effort to achieve these goals. First, normal auditory system development was studied in a parametric framework and the findings from that effort formed the basis of a comprehensive, phenomenological developmental model that was used to consider the development of nonlinear auditory mechanisms as well as the auditory consequences of hypothyroidism.
Creighton University
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