Cheatham, Mary Ann, PhD
Communication Sciences and Disorders
Frances Searle 2-240 Evanston
|Areas of Research||
|NU Scholar Profile|
|Recent Publications on PubMed|
Genetic Approaches to the Study of Cochlear Physiology
Over the last several decades, the Auditory Physiology Laboratory has engaged in the study of cochlear nonlinearities and their origins. These efforts began by characterizing stimulus-related, cochlear potentials recorded in fluid spaces within the cochlea. In order to evaluate contributions made by individual inner and outer hair cells to the gross cochlear potentials, a method was developed to record from single hair cells in the mammalian organ of Corti, the sense organ of hearing. A primary interest was the investigation of two-tone interactions, including two-tone suppression and intermodulation distortion.
This investigation of how signals are coded in the peripheral auditory system provides a foundation for further studies using the mouse in auditory research. Given that mice and humans carry several homologous genes for hereditary deafness, mice provide an important animal model for studying hearing loss of genetic origin, which affects at least 1 in 2000 births. In order to investigate the effect of targeted mutations on the development and maintenance of auditory function, we devised procedures that can be used with small animals, weighing ~15 grams. This expertise allows us to study cochlear function in mutant mice. For example, we have recorded from mice lacking the alpha 9 acetylcholine receptor. This knockout mouse is especially valuable for studying the influence of efferent innervation on outer hair cell (OHC) function, i.e., the influence of neural input from the central nervous system to the periphery. Transgenic animals are also advantageous when investigating the functional significance of the recently discovered motor protein, prestin. Our previous work demonstrated in vitro that prestin provides the molecular basis for OHC electromotility, the change in cell length observed during electrical stimulation. An in vivo animal model, however, is required in order to learn if this OHC behavior is responsible for the exquisite sensitivity and frequency selectivity observed in the mammalian cochlea. Because of the several mutagenesis programs now established worldwide, the numbers of genes associated with the inner ear will increase rapidly, thereby providing a genetic approach to the study of cochlear physiology.
Cheatham, MA, Low-Zeddies, S., Naik, K., Edge, R., Zheng, J., Anderson, CT and Dallos, P. (2009). A chimera analysis of prestin knock-out mice. J. Neurosci., 29, 12000-12008.