There are no direct, noninvasive, physiological measures of vestibular function. This is in clear contrast to the wide variety of physiological measures available to directly assess function of the auditory system at all levels from the end organ to the cortex. Many of these auditory measures, most notably, auditory brainstem responses, have been used to screen for, or identify and characterize hearing loss in a large number of genetic mutants. These studies have provided important information about the genetics of hearing impairment. The proposed research will develop the techniques to assess the functional status of the vestibular end organs and eighth nerve. Meaurements will be direct, noninvasive and implemented by adapting established techniques for recording linear vestibular evoked potentials. Protocols will be suitable for screening and detailed functional assessment.
Two specific aims will be addressed. First, stimulation and recording hardware and software will be developed. Peripheral vestibular and brainstem neural activity will be recorded using far-field evoked potential techniques. Adequate stimuli for activation of macular or ampullar neurons will be used to elicit responses. Stimuli will be applied to the cranium via a mechanical shaker/head mount system. Normal mice and genetic mutants with specific inner ear or central anomalies will be used to demonstrate test validity. Second, the effectiveness and efficiency of the measurement technique will be evaluated. Vestibular function will be surveyed based on two selection strategies. One strategy will measure mice that display behavioral signs of imbalance or vestibular dysfunction or have measurable hearing loss. The second strategy will measure random samples drawn from multiple genetic strains where vestibular dysfunction may be obscure or hidden . This research will produce a tool for the direct, noninvasive assessment of vestibular function and will generate a database quantifying vestibular function in relation to genetics. The knowledge gained will serve as a basis for future research ultimately leading to a better understanding of vestibular ontogeny, genetics of vestibular impairment and better diagnosis and treatment of dizziness in humans.
| Jones, Sherri M; Jones, Timothy A (2014) Genetics of peripheral vestibular dysfunction: lessons from mutant mouse strains. J Am Acad Audiol 25:289-301 |
| Jones, Timothy A; Jones, Sherri M; Vijayakumar, Sarath et al. (2011) The adequate stimulus for mammalian linear vestibular evoked potentials (VsEPs). Hear Res 280:133-40 |
| Gao, Jiangang; Maison, Stephane F; Wu, Xudong et al. (2007) Orphan glutamate receptor delta1 subunit required for high-frequency hearing. Mol Cell Biol 27:4500-12 |
| Jones, Sherri M; Jones, Timothy A; Johnson, Kenneth R et al. (2006) A comparison of vestibular and auditory phenotypes in inbred mouse strains. Brain Res 1091:40-6 |
| Hoffman, Larry F; Ross, Muriel D; Varelas, Joseph et al. (2006) Afferent synapses are present in utricular hair cells from otoconia-deficient mice. Hear Res 222:35-42 |
| Jones, Sherri M; Johnson, Kenneth R; Yu, Heping et al. (2005) A quantitative survey of gravity receptor function in mutant mouse strains. J Assoc Res Otolaryngol 6:297-310 |
| Alagramam, Kumar N; Stahl, John S; Jones, Sherri M et al. (2005) Characterization of vestibular dysfunction in the mouse model for Usher syndrome 1F. J Assoc Res Otolaryngol 6:106-18 |
| Jones, Sherri M; Erway, Lawrence C; Johnson, Kenneth R et al. (2004) Gravity receptor function in mice with graded otoconial deficiencies. Hear Res 191:34-40 |
| Fuller, P M; Jones, T A; Jones, S M et al. (2004) Evidence for macular gravity receptor modulation of hypothalamic, limbic and autonomic nuclei. Neuroscience 129:461-71 |
| Zhang, Zunyi; Zhang, Xiaoyun; Avniel, Wilma A et al. (2003) Malleal processus brevis is dispensable for normal hearing in mice. Dev Dyn 227:69-77 |
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