Abstracts Biological Sciences

Changes in the central auditory system with hearing loss

by Catherine Connelly

The goal of this thesis is to expand our understanding of central auditory nervous system plasticity following a hearing loss. This work focuses on the bushy cell (BC) population and its excitatory and inhibitory axosomatic inputs. BCs are located in the first central nucleus of the auditory pathway, the cochlear nucleus (CN), and receive direct input from auditory nerve fibers. BCs convey high fidelity and temporally precise timing cues embedded in sound. This study used complementary physiologic hearing tests and microscopic techniques in mice to study brain changes with hearing loss. The murine strains investigated include: hearing control CBA/Ca and heterozygous shaker-2 (sh2+/-) mice; early onset progressive hearing loss DBA/2 mice; and congenitally deaf homozygous shaker-2 (sh2-/-) mice. The large auditory nerve ending, the endbulb of Held (EB) is the main excitatory input to BCs. Anterograde dye injections in the auditory nerve stained fibers and EBs representing each strain at 1, 3, and 6 months of age. Counterstaining with basophilic dye allowed BC somata to be visualized as well. There was no significant difference in BC or EB size in the 1-month-old animals, indicating an uninterrupted development of these structures. However, in the animals with a hearing loss, both EBs and BCs exhibited a graded reduction in size that paralleled the hearing loss, with the most severe pathology seen in the deaf 6-month-old sh2-/- mice. Electron microscopy was used to study excitatory (glutamatergic and cholinergic) and inhibitory (glycinergic) terminals onto the BC soma following hearing loss in the older 3- and 6-month-old mouse cohorts. Structural features of BCs and their inputs show pathologies associated with degree and duration of hearing loss (i.e., excitatory and inhibitory terminal size and apposition, the ratio of excitatory to inhibitory terminal size and apposition, cistern size, and BC lysosome size), whereas other features appear to be more robust (i.e., mitochondrial fraction, postsynaptic density morphology and cholinergic terminal size and apposition). Overall, these data give clues to the neural underpinnings of symptoms associated with hearing loss, such as impaired signal extraction in the presence of noise and the emergence of tinnitus. The work also will aid in narrowing the scope of future treatment strategies for hearing loss. Advisors/Committee Members: Ryugo, David, Garvan Institute of Medical Research, Faculty of Medicine, UNSW, McMahon, Catherine, Macquarie University.