The Mouse Auditory Testing (MAT) Core Facility assists the Principle Investigators of the NIDCD and their collaborators with auditory testing in mice. Two physiological measures of auditory function are employed at the MAT Core: the auditory brainstem response (ABR) and distortion-product otoacoustic emissions (DPOAEs). The ABR is an evoked potential that can be used to estimate hearing thresholds. The ABR is measured by placing electrodes on the scalp and recording the potentials generated by the auditory nervous system when a sound is repeatedly presented to the ear. DPOAEs are soft sounds that are recorded in the ear canal and can be used to screen for hearing loss and to evaluate inner ear (cochlear) function. The presence of DPOAEs indicates normal function of outer hair cells in the inner ear. DPOAEs are measured by placing a small probe containing two speakers and a microphone in the opening of the ear canal. Two tones are played simultaneously to the ear, and the DPOAEs produced by the ear are recorded by the microphone. The facility also assists with protocols that require noise exposure. Dr. Fitzgerald trained 10 new investigators from the NIDCD and four investigators from the Blast-Induced Neurotrauma Branch at Walter Reed Army Institute of Research in auditory testing and auditory data analyses. An additional 13 investigators from the NIDCD continued training or received support from the MAT Core. Dr. Fitzgerald collaborated on and/or supported 30 projects conducted in seven NIDCD labs. Dr. Fitzgerald assisted with planning auditory test protocols, collection of auditory data, and analysis of auditory test data. Dr. Fitzgerald provided ongoing support such as equipment calibration, facility maintenance, and troubleshooting. Dr. Fitzgerald was a co-author on three manuscripts published this past year. Information on collaborations with specific laboratories is listed below. Inner Ear Gene Therapy Program; PI: Wade Chien, M.D. Dr. Fitzgerald collaborated on and/or supported nine projects investigating the use of gene therapy to remediate hearing loss. Dr. Fitzgerald assisted with preparation of two published manuscripts and one manuscript currently in review. Dr. Fitzgerald trained Joan Guitart (Post-Bac IRTA) and provided continued training/support to Kevin Isgrig (Biologist), Dr. Jasmine Saleh (Post-Doctoral IRTA Fellow), and Dr. Bovey Zhu (Special Volunteer). Section on Sensory Cell Biology; PI: Lisa Cunningham, Ph.D. Dr. Fitzgerald collaborated on and/or supported three projects examining the prevention of Cisplatin ototoxicity. Dr. Fitzgerald assisted with set-up and calibration of noise exposures for these experiments. Dr. Fitzgerald trained Katie Spielbauer (MRSP Fellow) and provided continued training/support to Aaron Rusheen (Post-Bac IRTA) and Dr. Katharine Fernandez (Staff Scientist). Laboratory of Molecular Genetics; PI: Thomas Friedman, Ph.D. Dr. Fitzgerald collaborated on five projects examining auditory function in various mutant mouse strains, including projects with Dr. Inna Belyantseva (Staff Scientist), Dr. Jonathan Bird (Visiting Post-Doctoral Fellow), Dr. Melanie Barzik (Staff Scientist), and Dr. Ayesha Imtiaz (Post-Doctoral Fellow). Dr. Fitzgerald assisted Dr. Robert Morell (Director, Genomics and Computational Biology Core) with three projects investigating auditory function in three strains of mutant mice. Dr. Fitzgerald assisted with set-up and calibration of noise exposure experiments. Dr. Fitzgerald began training with Risa Tona (Post-Doctoral Fellow) and Kerianne Richards (Bioinformatist, Genomics and Computational Biology Core) and provided continued training and/or support to Rabia Faridi (Pre-Doctoral Visiting Fellow), Alexis Oguh (Post-Bac IRTA), Daniel Sutton (Post-Bac IRTA), Elizabeth Thomason (Post-Bac IRTA), and Elizabeth Wilson Bernhard (Biologist). Dr. Fitzgerald and Elizabeth Wilson Bernhard continued work on a survey of auditory sensitivity with age in the Friedman lab C57BL/6J mouse colony. Testing of B6.CAST-Cdh23 Ahl+/Kjn mice is ongoing. Section on Molecular Biology and Genetics; PI: Andrew Griffith, M.D., Ph.D. Dr. Fitzgerald provided continued support to Dr. Ayako Nishio (Visiting Post-Doctoral Fellow) on two projects investigating Slc26A4 mutant mice. Dr. Fitzgerald assisted with preparation of a manuscript published in Neuroscience based on one of these projects. Dr. Fitzgerald collaborated on two additional projects on examining auditory function in Polg-D247A mutant mice and in Phex-Hyp-Duk mice. Dr. Fitzgerald trained Danielle Harrow (Biologist) and Astin Ross (Post-Doctoral IRTA Fellow) in auditory testing and data analyses. Laboratory of Auditory Restoration and Development; PI: Michael Hoa, M.D. Dr. Fitzgerald collaborated on a project investigating auditory and vestibular function in Sna1 mutant mice. Dr. Fitzgerald trained Dr. Rafal Olszewski (Biologist) in auditory testing and data analyses. Section on Structural Cell Biology; PI: Bechara Kachar, Ph.D. Dr. Fitzgerald began training with Robstein Chidavaenzi (Post-Doctoral Visiting Fellow) and Evan Krystofiak (Post-Doctoral IRTA Fellow) in auditory testing and data analyses. Laboratory of Cochlear Development; PI: Matthew Kelley, Ph.D. Dr. Fitzgerald collaborated with Dr. Elizabeth Driver (Staff Scientist) on a project investigating an inner hair cell-specific gene expressed during mouse cochlear development. Dr. Fitzgerald collaborated with Hanna Sherrill (Graduate Fellow) on a project investigating auditory function in Pou4f1 mutant mice. Dr. Fitzgerald consulted on experimental design, equipment setup, and pilot data collection for a collaboration between the Kelley lab and the Blast-Induced Neurotrauma Branch at Walter Reed Army Institute of Research on the effects of blast exposure on auditory and vestibular function in mice. Dr. Fitzgerald trained Elizabeth Driver, Stephen McInturff (Post-Bac IRTA), and Hanna Sherrill from the Kelley Lab and Rodrigo Urioste (Student), Dr. Yanling Wei, Yan Su, and Dr. Ying Wang from the Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience. Section on Neuronal Circuitry; PI: Catherine Weisz Dr. Fitzgerald consulted on experimental design and equipment for a future project on DPOAE suppression in mice in collaboration with Dr. Rebecca Seal (University of Pittsburgh). In July 2016, the MAT CORE participated in the second annual Earssentials, a week-long course designed to expose new trainees to auditory research at the NIDCD through lectures and laboratory exercises. Twelve students from the NIDCD and from outside the NIH participated in a laboratory training exercise on auditory testing in mice given by Dr. Fitzgerald and Elizabeth Wilson Bernhard. Development of a vestibular sensory evoked potentials (VsEPs) system continued this year. VsEPs are recorded by placing electrodes on the scalp, similar to an ABR, and recording the electrical potentials generated by the vestibular nervous system in response to linear movements of the head. Dr. Fitzgerald collaborated with Jessica Crouch (Student), John Kakareka (Electronics Engineer), and Thomas Pohida (Staff Scientist) from the Signal Processing and Instrumentation Section (SPIS) of the Computational Bioscience and Engineering Lab (CBEL) in the Center for Information Technology (CIT) on a custom-made component that converts acceleration to jerk for calibration of the stimulus. Since completion of that phase, Connor Schultz (Student), John Kakareka, and Thomas Pohida from SPIS and Elizabeth Wilson Bernhard have assisted with troubleshooting and pilot data collection.

Project Start
Project End
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Budget End
Support Year
5
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Deafness & Other Communication Disorders
Department
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Nakanishi, Hiroshi; Kurima, Kiyoto; Pan, Bifeng et al. (2018) Tmc2 expression partially restores auditory function in a mouse model of DFNB7/B11 deafness caused by loss of Tmc1 function. Sci Rep 8:12125
Imtiaz, Ayesha; Belyantseva, Inna A; Beirl, Alisha J et al. (2018) CDC14A phosphatase is essential for hearing and male fertility in mouse and human. Hum Mol Genet 27:780-798
Bird, Jonathan E; Barzik, Melanie; Drummond, Meghan C et al. (2017) Harnessing molecular motors for nanoscale pulldown in live cells. Mol Biol Cell 28:463-475
Breglio, Andrew M; Rusheen, Aaron E; Shide, Eric D et al. (2017) Cisplatin is retained in the cochlea indefinitely following chemotherapy. Nat Commun 8:1654
Tran, Linda; Allen, Clint T; Xiao, Roy et al. (2017) Cisplatin Alters Antitumor Immunity and Synergizes with PD-1/PD-L1 Inhibition in Head and Neck Squamous Cell Carcinoma. Cancer Immunol Res 5:1141-1151
Isgrig, Kevin; Shteamer, Jack W; Belyantseva, Inna A et al. (2017) Gene Therapy Restores Balance and Auditory Functions in a Mouse Model of Usher Syndrome. Mol Ther 25:780-791
Nishio, Ayako; Ito, Taku; Cheng, Hui et al. (2016) Slc26a4 expression prevents fluctuation of hearing in a mouse model of large vestibular aqueduct syndrome. Neuroscience 329:74-82
Chien, Wade W; McDougald, Devin S; Roy, Soumen et al. (2015) Cochlear gene transfer mediated by adeno-associated virus: Comparison of two surgical approaches. Laryngoscope :
Morozko, Eva L; Nishio, Ayako; Ingham, Neil J et al. (2015) ILDR1 null mice, a model of human deafness DFNB42, show structural aberrations of tricellular tight junctions and degeneration of auditory hair cells. Hum Mol Genet 24:609-24
Chien, Wade W; Isgrig, Kevin; Roy, Soumen et al. (2015) Gene therapy restores hair cell stereocilia morphology in inner ears of deaf whirler mice. Mol Ther :

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