Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Date of Award

Spring 2016

Document Type

Dissertation

Degree Name

Doctor of Audiology (AuD)

Department

Department of Communication Sciences and Disorders

Advisor(s)

Lincoln C. Gray

Abstract

Neural pathways underlie the ability of the auditory system to perceive sound. Organization of neural pathways into functional auditory circuitry is accomplished in part by Eph and ephrin signaling proteins. One of these signaling proteins, the EphA4 receptor tyrosine kinase protein, acts as an axon-guidance molecule to aid in target selection and to maintain tonotopicity in the auditory brainstem and midbrain. Genetic mutations of the EphA4 protein have been shown to affect structural auditory development, but there is limited research which shows the functional effects of these mutations. The goal of the present study was to determine the functional effects of EphA4 lacZ mutations on auditory processing using physiologic measures. Auditory Brainstem Response (ABR) measures including summating potential (SP) amplitude were recorded in EphA4 lacZ mutant mice (with C57BL/6J background strain) prior to three months of age and compared to a control group of wild-type littermates. ABR wave latency and threshold analysis in heterozygous mice showed no significant differences from controls.

Comparison of homozygous mutant mice to wild-type controls showed significantly elevated (poorer) ABR thresholds in the homozygous group for 8 kHz tone-burst, 12 kHz tone-burst, and click stimuli. SP amplitudes were increased in the homozygous group suggesting mutation related changes to the auditory system. Deficits in auditory function seen in the homozygous mutant strain provide evidence that normal EphA4 expression is necessary for normal auditory function. Preserved function in the heterozygous mutants suggests that one allele is sufficient for normal function at approximately one to three months of age. Our findings support the role of EphA4 in the development of the auditory function.

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