Understanding the underlying mechanisms of noise-induced hearing loss : a molecular and physiological approach

Abstract

The main purpose of this thesis was to investigate the physiological, molecular and behavioural consequences of unilateral noise-induced hearing loss. In particular, how these properties develop in the month following noise-induced hearing loss. These investigations have implications for the generation of associated acoustic disorders, such as tinnitus and possibly hyperacusis. Tinnitus is the sensation of a sound when no external sound source is present. It is estimated to affect 10-17% of adults worldwide. There are many ways in which tinnitus can be generated; however noise-induced hearing loss is the most common cause and is increasingly apparent in individuals across all age groups. Most individuals in today's society are exposed to damaging levels of noise on a regular basis; at the workplace, at concerts and the use of personal listening devices. It is understood that tinnitus is a disorder of the auditory system, but the neural mechanisms remain unknown. Excessive levels of noise can cause damage to the cochlea, which can result in premature deafness and noise-induced hearing loss. This damage causes a range of changes in the auditory pathway. Changes observed include plasticity of tonotopic representation, changes in auditory neuron physiology, changes in the pattern of spontaneous activity and changes in the balance of excitatory and inhibitory transmitter systems. Moreover, damage to the cochlea frequently results in tinnitus. This suggests that one or more of these changes may be involved in tinnitus generation. This thesis has investigated the one month time-course changes of molecular, physiological and behavioural changes in the young adult rat after NIHL. This investigation has presented novel findings that significant time-dependent changes occur in the auditory pathway after NIHL. The physiological changes over the one month time-course reflect a constant compensatory mechanism between excitability and SA; the molecular changes indicate fluctuations in excitatory and inhibitory neurotransmission-related systems over the one month time-course and the behavioural manifestations of tinnitus highlight the variability of animals' perceptions after NIHL. This study has proposed that the Day 8 time-point may be a crucial period after NIHL, whereby the auditory system attains a state of partial recovery. Interpreting these mechanisms will be crucial for understanding the generation and development of acoustic disorders such as tinnitus and hyperacusis, and potentially the development of a therapeutic intervention.

Date of Award	2012
Original language	English