Date

February 2012

Document Type

Dissertation

Degree Name

Ph.D.

Institution

Oregon Health & Science University

Abstract

Inner ear hair cells are required for our senses of hearing, balance, and acceleration. Because hair cells do not regenerate in humans, life-long maintenance and repair of these cells directly influences age-related hearing loss, yet we do not fully understand the molecular processes that govern normal cellular activity or a cell’s response to and recovery from damage. This thesis characterizes hair-cell energy metabolism in chicken auditory and vestibular organs, and explores the cellular response to hair-bundle tip link damage. Chapter 1 gives a background of the relevant literature on energy metabolism and the tip link, highlighting what information is lacking and how the experiments on this thesis will advance our understanding. Chapter 2 presents a complete molecular characterization of the utricle and cochlear epithelium, which revealed that the cochlea up-regulates the glycolytic energy production pathway. Chapter 3 presents data on the fate of the tip link proteins CDH23 and PCDH15 following tip link breakage, using immunohistochemistry and scanning electron microscopy to examine tip links. Evidence is presented for the redistribution and intracellular co-localization of CDH23 and PCDH15 upon tip link breakage. Chapter 4 describes a novel method of calcium imaging in the chicken cochlea, using a cell-permeable dye to simultaneously monitor intracellular calcium in many hair cells following tip link breakage and pharmacological manipulation. Combined, this thesis uncovers tissue-specific pathways for inner ear energy metabolism and provides new evidence for how the hair cell responds to damage of the mechanosensory organ.

Identifier

doi:10.6083/M4XG9P5Z

Division

Neuroscience Graduate Program

School

School of Medicine

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