The AHRF Board of Directors and the Research Committee are pleased to announce this year’s AHRF research grant recipients. AHRF received numerous high-quality proposals this year; therefore, we decided to fund seven research projects, two more than last year and one more than the average year. A report on the project and an accounting of funds is required at the end of the funding period, and projects are generally funded for one year unless an exception is made at the discretion of the Foundation. In addition to the seven grants awarded by AHRF in 2014, we also fund one $25,000 grant in conjunction with CORE. The AHRF grant program focuses on supporting new or beginning investigators so that they can test ideas and collect data as their research evolves. We are very pleased to introduce the recipients of the 2014 AHRF research grants and we look forward to the exciting results of these highly innovative projects!
Zonal Variations in Calyx properties of the Crista
Katherine Rennie, PhD – University of Colorado, Denver
The goal of Dr. Rennie’s research project is to elucidate mechanisms of synaptic transmission and plasticity at the vestibular type I hair cell/calyx synapse. Type I hair cells have unique characteristics including a low-voltage activated K+ conductance, an unusual afferent calyx terminal that surrounds most of the hair cell’s basolateral membrane, and a greater sensitivity to certain ototoxic drugs compared to other types of hair cells. The number of ribbon synapses within vestibular hair cells is known to vary across the rodent crista and afferent fibers in different zones have different responses to rotational stimuli. However, the underlying mechanisms driving synaptic transmission remain unknown. Dr. Rennie will use patch clamp and imaging techniques to study transmitter release from labeled synaptic ribbons at the rodent type I hair cell/calyx synapse. Variations in ribbon synapse numbers may have a measurable impact on glutamate release and postsynaptic responses. The role of ionic conductances in firing in calyx terminals will also be determined. Regional variations in K+ channels will be studied to better understand how they function to process vestibular signals. Defects in K+ fluxes are implicated in certain vestibular disorders including Meniere’s disease, a debilitating condition characterized by episodes of vertigo. Studying ion channels in selective groups of hair cells and afferents will provide new information on processing and will help to identify future therapeutic targets for the treatment of inner ear disorders such as Meniere’s.
Effects of Dexamethasone on Radiation Induced Auditory Hair Cell and Hearing Losses
Christine Dinh, MD – University of Miami Miller School of Medicine
The objective of Dr. Dinh’s study is to investigate the effectiveness of dexamethasone (DXM) in preventing radiation induced auditory hair cell loss in vitro and radiation induced sensorineural hearing loss in vivo. This research project is part of a larger and more comprehensive translational research study involving the testing of various intratympanic therapies for the treatment of cisplatin, radiation, and combined cisplatin and radiation induced hearing loss. The results of this study will produce preliminary data necessary for further research through a prospective randomized, double-blind clinical trial testing the effects of several otoprotective agents against cisplatin and radiation induced hearing loss.
Cellular and Molecular Characterization of a Novel Human Deafness Dominant Mutation in Myosin IIIa
M’hamed Grati, PhD – University of Miami Miller School of Medicine
The goals of this research project include the study of the pathogenicity of this novel predicted dominant point mutation by examining its effect on myosin IIIa motility and espin-1 transport in COS7 cells, as well as its effect on myosin IIIb motility; express mutant myosin IIIa in organotypic hair cells and examine its subcellular localization, motility, and effects on hair cell stereocilia morphology; to generate transgenic mice expressing mutant myosin IIIa and evaluate, by auditory brainstem recordings and distortion product otoacoustic emissions, its effect on hearing in these mice, closely examining by whole-mount immunofluorescence and by scanning electron microscopy the morphology of their hair cell stereocilia bundle development looking for anomalies, as well as investigating by whole-mount immunofluorescence the potential deficiency in transport and the distribution of select stereocilia tip proteins.
Statistical Learning from Acoustical Simulations of Cochlear Implants
Tina Grieco-Calub, PhD and Casey Lew-Williams, PhD – Northwestern University
Drs. Grieco-Calub and Lew-Williams will test the hypothesis that fine frequency resolution is required for successful auditory statistical learning. In a series of experiments with normal hearing infants and adults, the investigators will determine whether it is possible to segment words from spectrally degraded speech. The outcomes of the experiments will converge to inform future research exploring statistical learning abilities in infants and adults with cochlear implants, with the ultimate goal of improving aural habilitation programs.Behavioral Testing for Hidden Hearing Loss in Chinchillas: Towards Human Diagnostics
Behavioral Testing for Hidden Hearing Loss in Chinchillas: Towards Human Diagnostics
Ann E. Hickox, PhD and Michael G. Heinz, PhD – Purdue University
Drs. Hickox and Heinz will measure physiological and behavioral signs of hidden hearing loss on a chinchilla model and, within the same individual animals, assess the relationship between physiological damage and perceptual consequences. The timelines and methods of the project are designed for immediate application to a large-scale study of hidden hearing loss and the development of diagnostic assays, led by Dr. Chris Plack at the University of Manchester in the United Kingdom. By combining invasive histological analysis, available in the animal model, with electrophysiology and behavioral tasks that are applicable to both animal and human listeners, the study in chinchillas can directly address the hypothesis that a history of noise exposure leads to perceptual deficits based in hidden auditory nerve damage. Collaborative efforts with the team in the U.K. ensures that results from the chinchilla model will directly and immediately inform the design of the human-subject studies, and ultimately contribute to the development of new and more sensitive clinical diagnostics.
Role of Resident Immune Cells in the Development of Cochlear Innervation
Tejbeer Kaur, PhD and Mark Rutherford, PhD – Washington University School of Medicine
Recent work in the developing central nervous system has demonstrated that selective synaptic pruning involves the activity of microglia, the macrophages of the brain. Using a genetically engineered mouse model in which all macrophages are labeled with green fluorescent protein, the researchers have observed a large population of resident macrophages in the developing organ of Corti. However, the possible role of these cells in synaptic pruning and refinement has not been explored. Through this project, Drs. Kaur and Rutherford will determine whether macrophages in the developing cochlea are involved in the developmental refinement of cochlear innervation. The study will test for this unprecedented role of macrophages by depleting them, using both pharmacological and genetic approaches, during the postnatal period of cochlear development. This work will quantify synapse numbers and innervation patterns, and also assess auditory function after macrophage depletion. The outcomes of the experiments will indicate whether macrophages play an essential role in the refinement of cochlear innervation and may provide new insights into the nature of cellular dialogue between the innate immune system and the inner ear.
Central Neurophysiological Markers Underlying Degraded Speech Recognition
Gavin M. Bidelman, PhD – School of Communication Sciences & Disorders, University of Memphis
Extracting speech from background noise is fundamental for real-world communication as everyday listening environments, such as noisy classrooms and restaurants, contain competing sounds. Recognizing speech within the auditory scene is challenged by two types of acoustic interference: noise and reverberation. These interferences are particularly problematic for elderly and hearing impaired people who perform poorer in noise than their hearing loss would predict. While modern hearing aids provide audibility, they fail to restore speech intelligibility in noisy/reverberant settings. Advancements in assistive hearing technologies could be dramatically improved with knowledge of how central brain mechanisms affect speech coding in adverse listening situations. The long-term goal of Dr. Bidelman’s research project is to elucidate the neural substrates that contribute and interact to yield robust perceptual abilities. The project results will offer new and fresh insights for improved auditory prostheses and signal processing strategies by evaluating how noise and reverberation each affect the neural correlates of speech at multiple computational levels of the auditory pathway.