The Mouse Auditory Testing (MAT) Core facility assists NIDCD investigators and their collaborators with auditory and vestibular function 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. DPOAEs are soft sounds that are recorded in the ear canal using a small microphone. DPOAEs can be used to screen for hearing loss and to evaluate inner ear function; specifically, the presence of DPOAEs indicates normal function of outer hair cells in the inner ear. Otoscopy and tympanometry/wide-band absorbance measures are available to assist in suspected cases of outer and middle ear pathology. Otoscopy with a surgical microscope allows visualization of the pinna, external auditory canal, and tympanic membrane for signs of pathology. Tympanometry and wide-band absorbance measures assess middle-ear function. The facility also assists with noise exposure protocols as needed. Vestibular sensory evoked potentials (VsEPs) are measured to assess vestibular function in mice. VsEPs are recorded by placing electrodes on the scalp and recording the electrical potentials generated by the vestibular nervous system in response to linear movements of the head. Normative and experimental data collection using the VsEP system continued this year under the direction of Dr. Talah Wafa (Post-Doctoral Fellow). Dr. Fitzgerald began or continued training in auditory function testing with seven NIDCD investigators. Dr. Wafa began or continued training in vestibular function testing with five NIDCD investigators. Six investigators completed auditory function testing independently but received support from the MAT Core. Dr. Fitzgerald trained/consulted with three investigators from other NIH Institutes (NINDS, NIA) regarding auditory testing and/or data analyses. Dr. Fitzgerald provided training through observation and consulted on auditory function testing with two investigators from the lab of Dr. Thomas Coate at Georgetown University. Dr. Fitzgerald and Dr. Wafa provided training through observation and consulted on vestibular function testing with 13 investigators from five programs outside the NIH (Kyoto University, Japan; Ohio State University; Tokyo Medical and Dental University, Japan; Walter Reed Army Institute of Research; Washington University in St. Louis). Dr. Fitzgerald and Dr. Wafa collaborated on and/or supported projects conducted in six NIDCD labs. Dr. Fitzgerald collaborated on two projects from labs in other NIH institutes (NINDS, NIA). Dr. Fitzgerald was a co-author on four manuscripts published this past year. Dr. Wafa was a co-author on two of the manuscripts. Information on collaborations with specific laboratories is listed below. Inner Ear Gene Therapy Program (PI: Wade Chien, M.D.) Dr. Wafa began training Kevin Isgrig (Biologist) in vestibular function testing. Dr. Fitzgerald provided support to Kevin Isgrig and Jianliang Zhu (Biologist) for seven ongoing projects investigating the use of gene therapy to remediate hearing loss that included auditory function testing. Auditory function data for two manuscripts published in FY2019 were collected in the MAT Core: Mookherjee, S, Chen, HY, Isgrig, K, Yu, W, Hiriyanna, S, Levron, R, Li, T, Colosi, P, Chien, W, Swaroop, A, Wu, Z (2018). A CEP290 C-Terminal domain complements the mutant CEP290 of Rd16 mice in trans and rescues retinal degeneration. Cell Rep, 25(3), 611-623.e6. (doi: 10.1016/j.celrep.2018.09.043). Isgrig, K, McDougald, DS, Zhu, J, Wang, HJ, Bennett, J, Chien, WW (2019). AAV2.7m8 is a powerful viral vector for inner ear gene therapy. Nature Commun, 10(1), 427. (doi: 10.1038/s41467-018-08243-1). Section on Sensory Cell Biology (PI: Lisa Cunningham, Ph.D.) Dr. Fitzgerald continued training with Ben Gersten (Post-Bac IRTA) in auditory function testing and data analyses. Dr. Fitzgerald provided support to Dr. Katharine Fernandez (Staff Scientist) and Ben Gersten for three projects investigating ototoxicity of Cisplatin and other chemotherapeutic drugs. Dr. Wafa assisted Dr. Fernandez with vestibular function testing for one of these projects. Dr. Fitzgerald and Dr. Wafa assisted with preparation of a one published manuscript. Laboratory of Molecular Genetics (PI: Thomas Friedman, Ph.D.) Dr. Fitzgerald collaborated on eight projects examining auditory and/or vestibular function in various mutant mouse strains, including projects with Dr. Inna Belyantseva (Staff Scientist), Rabia Faridi (Pre-Doctoral Visiting Fellow), Dr. Ayesha Imtiaz (Post-Doctoral Visiting Fellow), Dr. Risa Tona (Post-Doctoral Visiting Fellow), Elizabeth Wilson Bernhard (Biologist), and Dr. Rizwan Yousaf (Research Fellow). Dr. Fitzgerald trained Wenqian Chen (Post-Bac IRTA) and Dr. Yousaf in auditory function testing. Dr. Fitzgerald assisted with preparation of two published manuscripts. Dr. Wafa also assisted with preparation of one of these manuscripts. Section on Molecular Biology and Genetics (PI: Andrew Griffith, M.D., Ph.D.) Dr. Fitzgerald trained Dr. Pragya Prakash (Post-Doctoral Visiting Fellow) in auditory testing and data analyses for her project on mutant mice. Dr. Fitzgerald collaborated with Danielle Harrow (Biologist) and Dr. Isabelle Roux (Staff Scientist) on a second set of vestibular function testing equipment for a project on a mutant mouse model. Dr. Wafa trained Danielle Harrow in vestibular function testing. Dr. Fitzgerald supported Danielle Harrow for her project examining auditory function in mutant mice. Laboratory of Cochlear Development (PI: Matthew Kelley, Ph.D.) Dr. Fitzgerald trained Dr. Braulio Peguero (Post-doctoral Fellow) in auditory testing for a project investigating mutant mice. Dr. Wafa began training in vestibular function testing and data analysis with Dr. Peguero. Dr. Fitzgerald and Dr. Wafa collaborated with Dr. Beatrice Mao (Post-doctoral Fellow) and Tara Balasubrumanian (Post-bac IRTA) on a project investigating the effects of blast trauma on auditory and vestibular function in mice completed as part of a collaboration with the Blast-Induced Neurotrauma Branch at the Walter Reed Army Institute of Research. Dr. Fitzgerald assisted with preparation of a one published manuscript. Section on Sensory Cell Regeneration and Development (PI: Doris Wu, Ph.D.) Dr. Wafa and Dr. Fitzgerald collaborated with Dr. Kazuya Ono (Post-Doctoral Visiting Fellow) and Dr. Yosuke Tona (Post-Doctoral Visiting Fellow) on two projects examining auditory and/or vestibular function in conditional knockout mice. Laboratory of Molecular Gerontology, NIA (PI: Vilhelm Bohr, M.D., Ph.D.) Dr. Fitzgerald collaborated with M. Nazir Okur (Post-Doctoral Fellow) on a project on a mouse model of Cockayne Syndrome (CS) conducted in collaboration with the Kelley Lab. Dr. Fitzgerald trained Dr. Okur and Risako Kimura (Post-Bac IRTA) in auditory function testing data analyses. Molecular Physiology and Biophysics Section, NINDS (PI: Kenton Swartz, Ph.D.) Dr. Fitzgerald trained Dr. Angela Ballesteros Morcillo (Post-Doctoral Fellow) in auditory function testing and data analyses for a project on transgenic mice. In July 2019, the MAT Core participated in the annual Earssentials workshop, a week-long course designed to expose new trainees to auditory research at the NIDCD through lectures and laboratory exercises. Twelve students participated in a laboratory training exercise on auditory testing in mice given by Dr. Fitzgerald, Elizabeth Wilson Bernhard, and Dr. Katharine Fernandez.
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