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Predisposition to hearing loss in different strains of mouse

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posted on 15.05.2015, 12:59 by James Langley Sinclair
This investigation explores the basis of the susceptibility to hearing loss from a neurobiological stand point, in different genetically modified and inbred strains of mice: CBA/Ca (CBA), C57BL/6J (C57), Kv2.2 knock-out (Kv2.2 KO) and USP42 KO. Kv2.2, a delayed rectifier potassium channel, is expressed in the ventral nucleus of the trapezoid body (VNTB) in the auditory brainstem, in which originates the medial olivocochlear system (MOC), an efferent system which protects and regulates the cochlea. Preventing expression of Kv2.2 predisposes mice to noise induced hearing loss. Labelling experiments presented here show Kv2.2 expressing neurons in the VNTB contribute to the population of MOC neurons, implicating regulation of excitability of MOC neurons in protection from hearing loss. The MOC system of the C57 is ineffective, thought to lend this strain predisposition to noise-induced and age-related hearing loss. Whole cell patch clamp was used to compare VNTB neurons of the C57 with those of the CBA, a different inbred strain with an effective MOC, in order to determine if differences in excitability exist between strains that may explain the differing strength of their respective MOC systems. Pre-hearing onset, the neurons of the VNTB were identical. Post hearing onset, electrophysiological characteristics diverged: the VNTB neurons of the CBA were able to support higher firing rates due to slower inactivation of its voltage-gated potassium currents. The role of inflammation in hair cell loss in the C57 was probed by knocking out USP42, a gene involved in cell-cycle arrest in response to metabolic damage, highlighting changes in the cochlear nuclei following peripheral loss of sensitivity. The changes observed in the VNTB and cochlear nuclei highlight the importance of activity dependent changes and homeostatic regulation of excitability in the central auditory system.

History

Supervisor(s)

Forsythe, Ian

Date of award

01/04/2015

Author affiliation

Department of Cell Physiology and Pharmacology

Awarding institution

University of Leicester

Qualification level

Doctoral

Qualification name

PhD

Language

en

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