The present work seeks to advance quantitative understanding of semicircular canal biomechanics under both physiological and pathological conditions with the goals of 1) improving the assessment and treatment of benign paroxysmal positional vertigo (BPPV) and 2) furthering the basic understanding of micromechanical and hair cell electro-mechanical factors in the process of angular motion sensation. Specifically, the work aims to: quantify the three-dimensional substrates of canalolithiasis and its relationship to BPPV, determine micromechanical contributions to spatial diversity in hair-cell activation and afferent response dynamics and, establish the role of hair-cell electro-mechanical feedback in the crista ampullaris.
The first aim will detail biomechanical and neural responses under conditions of experimentally induced canalolithiasis during provocative diagnostic tests and during canalith repositioning procedures.
The second aim will determine micromechanical and hair cell transduction current contributions to the diverse neural code transmitted from the semicircular canals to the brain. Regional differences in cupula motion will be measured during sinusoidal and step stimuli using a laser interferometer. The spatial distribution of haircell transduction currents will be mapped across the sensory epithelium and compared to micromechanical data to determine the relative contributions of each. Experiments to investigate the role of hair cell/bundle electro-motility will be included.
The third aim will investigate the influence of activation of the efferent vestibular system and, separately, electrical polarization of the endolymph on hair-cell and micromechanical responses. Detailed mathematical models will be used extensively to interpret results and direct the experimental studies. Computer models and animations showing responses to clinical diagnostic tests and canalith repositioning procedures will be generated. Results are expected to have immediate relevance to health and the human condition through the assessment and treatment of classical and non-classical BPPV as well as long-term significance enhancing basic understanding of semicircular canal micro-mechanics, haircell transduction and electro-mechanical feedback.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC006685-02
Application #
6995202
Study Section
Auditory System Study Section (AUD)
Program Officer
Platt, Christopher
Project Start
2004-12-15
Project End
2007-11-30
Budget Start
2005-12-01
Budget End
2006-11-30
Support Year
2
Fiscal Year
2006
Total Cost
$407,204
Indirect Cost
Name
University of Utah
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Poppi, Lauren A; Tabatabaee, Hessam; Drury, Hannah R et al. (2018) ACh-induced hyperpolarization and decreased resistance in mammalian type II vestibular hair cells. J Neurophysiol 119:312-325
Iversen, M M; Zhu, H; Zhou, W et al. (2018) Sound abnormally stimulates the vestibular system in canal dehiscence syndrome by generating pathological fluid-mechanical waves. Sci Rep 8:10257
Iversen, Marta M; Rabbitt, Richard D (2017) Wave Mechanics of the Vestibular Semicircular Canals. Biophys J 113:1133-1149
Iversen, M M; Christensen, D A; Parker, D L et al. (2017) Low-intensity ultrasound activates vestibular otolith organs through acoustic radiation force. J Acoust Soc Am 141:4209
Rabbitt, Richard D; Brichta, Alan M; Tabatabaee, Hessam et al. (2016) Heat pulse excitability of vestibular hair cells and afferent neurons. J Neurophysiol 116:825-43
Holman, Holly A; Tran, Vy M; Kalita, Mausam et al. (2016) BODIPY-Conjugated Xyloside Primes Fluorescent Glycosaminoglycans in the Inner Ear of Opsanus tau. J Assoc Res Otolaryngol 17:525-540
Highstein, Stephen M; Mann, Mary Anne; Holstein, Gay R et al. (2015) The quantal component of synaptic transmission from sensory hair cells to the vestibular calyx. J Neurophysiol 113:3827-35
Highstein, Stephen M; Holstein, Gay R; Mann, Mary Anne et al. (2014) Evidence that protons act as neurotransmitters at vestibular hair cell-calyx afferent synapses. Proc Natl Acad Sci U S A 111:5421-6
Zhu, Hong; Tang, Xuehui; Wei, Wei et al. (2014) Input-output functions of vestibular afferent responses to air-conducted clicks in rats. J Assoc Res Otolaryngol 15:73-86
Lumbreras, Vicente; Bas, Esperanza; Gupta, Chhavi et al. (2014) Pulsed infrared radiation excites cultured neonatal spiral and vestibular ganglion neurons by modulating mitochondrial calcium cycling. J Neurophysiol 112:1246-55

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