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Open Access Publications from the University of California

Cortical Processing of Frequency Modulated Sweeps in a Mouse Model of Presbycusis

  • Author(s): Trujillo, Michael
  • Advisor(s): Razak, Khaleel A
  • et al.

The population over the age of 65 years old is rapidly increasing around the world. Presbycusis (age-related hearing loss) is one of the most prevalent disabilities associated with age and can impair speech understanding and social and emotional well-being. Deficits in auditory processing, including speech understanding are likely caused by an interaction between changes in the way the brain processes sound and peripheral sensory hearing loss. It is difficult to disambiguate changes that occur within the brain independent of peripheral hearing loss and those that change because of it. To that end, this dissertation provides a framework for beginning to tease out how the relative contributions of peripheral sensory hearing loss (loss of cochlear hair cells) on cortical processing of frequency modulated (FM) sweeps in a mouse model of presbycusis (strain C57/bl6). FM sweeps are sounds that change in frequency over time. Human language and animal vocalizations contain FM sweeps. The genetic engineering tools present in the mouse make it a suitable model for probing the genetic roots and underlying mechanisms of neural dysfunction, such as is seen in presbycusis.

This C57/bl6 mouse strain undergoes predictable high frequency hearing loss by 6 months of age, continuing to profound hearing loss by 12 months of age. The purpose of this dissertation was to establish cortical response properties to FM sweeps as a function of age in a mouse model of presbycusis. Three experiments were performed. In the first experiment, FM sweep response properties were profiled in the young adult core auditory cortex. The main findings of the first experiment indicate that the young adult mouse auditory cortex is selective for a narrow range of FM sweep rates (between 0.5 and 3 kHz/msec) and this selectivity is depth dependent, suggesting FM sweep processing undergoes changes within the a cortical column. The second experiment explored the mechanisms that shape FM sweep rate selectivity. The main findings of the second experiment were that two mechanisms shape FM sweep rate selectivity in the young adult cortex, duration tuning for tones and sideband inhibition. Sideband inhibition is the dominant mechanism in the auditory cortex, shaping FM sweep rate selectivity in approximately 84% of neurons tested. Duration tuning shaped FM sweep rate selectivity in approximately 34% of neurons tested. The third experiment compared direction selectivity, FM rate selectivity, variability, and mechanisms between three age groups, young (1 - 3 months), middle (6-8 months), and old (14 - 20 months). The main findings of the third experiment were that presbycusis results in decreased selectivity, slowed FM rate selectivity, increased variability and decreased reliance on sideband inhibition. The results of these studies serve as a framework for comparisons with mouse strains who do not experience age-related hearing loss.

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