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Principal Investigator: Anders Fridberger
Organization: OREGON HEALTH & SCIENCE UNIVERSITY
Fiscal Year: 2024
Award: $575,351
Funding agency: National Institute on Deafness and Other Communication Disorders
Project Summary
A goal of the cochlear physiology laboratory is to understand how the components of the organ of Corti tune the
sound induced vibration of the organ of Corti. A process known as cochlear amplification (CA), now the subject
of intense work around the world, has critical components not yet studied. Two questions of broad interest that
this proposal address are; 1) how does the fundamental hydrodynamic viscosity contribute to the unique
frequency analysis capacity of the cochlear apex where speech frequencies are processed and 2) does the
tectorial membrane in have a central and biochemical role in regulating the calcium ion concentration that is so
critical to hair cell function. There are three Aims.
New and innovative experimental approaches are needed to address these questions. For the measurement of
output variables, we continue to use the optical coherence tomography (OCT) method, that we pioneered, to
record inner ear tissue vibration. We use state of the art confocal imaging methods applied to whole organ
explant systems and measure calcium ion concentrations in quiescent and stimulated inner ears.
In Aim 1, about question 1, we also propose to determine if perilymph macroscopic viscosity is a crucial
parameter of apical frequency tuning. As well as whether the tuning is dependent upon the process of cochlear
amplification within the traveling wave as it propagates to the apex. To manipulate viscosity, normal perilymph
is replaced with altered viscosity perilymph via a real time perfusion system. Aims 2 and 3 are about question 2
where we seek to understand how and with what consequence is calcium stored by the tectorial membrane.
Involved is the use of mutant mural models of defective tectorial membrane structural proteins and quantitative
fluorescent determination of calcium concentrations in endolymph and tectorial membrane. Additionally, in Aim
3, we explore how age might factor into the tectorial membrane calcium sequestration via two models that
manipulate the physiology of the stria vascularis a known target of age degeneration. Model 1 is the chronic
application of furosemide, an agent to suppress endocochlear potential. Model 2 is the genetically targeted
chemical alteration of stria vascularis blood flow). Taken together the work will significantly advance not only
fundamental knowledge of organ of Corti function but open a path to pharmacological interventions to treat
tectorial membrane calcium pathology.
Terms: <Address><Age><Animals><Apical><Auditory><Auditory Physiology><Basilar Membrane><Bass><Binding Sites><Biochemical><Biologic Models><Biological Models><Blood flow><Body Tissues><Buffers><Calcium><Calcium ion><Cell Body><Cell Function><Cell Physiology><Cell Process><Cells><Cellular Function><Cellular Physiology><Cellular Process><Charge><Chemicals><Chronic><Clinical><Cochlea><Cochlear Implants><Cochlear Organ><Cochlear Prosthesis><Combining Site><Corti Cell><Cortis Organ><Data><Development><Doppler OCT><Dysfunction><Endolymph><Environment><Extracellular Fluid><Frequencies><Frusemid><Functional disorder><Furosemide><Fursemide><Future><Goals><Hair Cells><Hearing><Hearing Loss><High Frequency Deafness><High-Frequency Hearing Loss><Human><Hypoacuses><Hypoacusis><In Vitro><Internal Ear><Intervention><Intervention Strategies><Knowledge><Laboratories><Labyrinth><Link><Liquid substance><Location><Measurement><Measures><Mechanics><Methods><Model System><Modeling><Modern Man><Modiolus><Molecular><Motion><Mutant Strains Mice><Nature><Neurosciences><OCT Tomography><Optical Coherence Tomography><Organ><Organ of Corti><Output><Pathology><Perfusion><Perilymph><Physiologic><Physiological><Physiology><Physiopathology><Presbyacusis><Presbycusis><Process><Property><Proteins><Pump><Reactive Site><Regulation><Research><Rest><Role><Sensory><Site><Speech><Spiral Organ><Spiral Organ of Corti><Stimulus><Stria Vascularis><Structural Protein><Structure><Subcellular Process><System><Techniques><Time><Tissues><Travel><Viscosity><Wood><Wood material><Work><age associated hearing loss><age induced hearing loss><age related decline in hearing><age related hearing deficits><age related hearing impairment><age related hearing loss><ages><aging associated hearing loss><aging induced hearing loss><aging related decline in hearing><aging related hearing deficits><aging related hearing impairment><aging related hearing loss><confocal imaging><correctional system><design><designing><developmental><deviancy><deviant><dysfunctional hearing><ear hair cell><experiment><experimental research><experimental study><experiments><fluid><good hearing><healthy hearing><hearing challenged><hearing defect><hearing deficient><hearing deficit><hearing difficulty><hearing dysfunction><hearing impairment><hearing loss therapy><hearing loss treatment><helicotrema><image-based method><imaging method><imaging modality><in vivo><inner ear><innovate><innovation><innovative><insight><interest><interventional strategy><liquid><mechanic><mechanical><minimally invasive><mouse mutant><mutant><normal hearing><novel><optical Doppler tomography><optical coherence Doppler tomography><pathophysiology><pharmacologic><pressure><response><social role><sound><sound frequency><stem><tectorial membrane><theories><treatment for hearing loss><treatment strategy><vibration>