| Popis: |
Tinnitus, often defined as the perception of sound in the absence of an external stimulus, affects millions of people worldwide and, in extreme cases, can be severely debilitating. While certain changes within the auditory system have been linked to tinnitus, the exact underlying causes of the phenomenon have not, as yet, been elucidated. Animal models of tinnitus have considerably furthered understanding of the some of the changes associated with the condition, allowing researchers to examine changes following noise exposure, the most common trigger for tinnitus. This thesis documents the development of an animal model of tinnitus, using the guinea pig to examine neural changes following induction of tinnitus. In the first study, a novel adaptation of a behavioural test was developed, in order to be able to determine whether guinea pigs were experiencing tinnitus following the administration of sodium salicylate, a common inducer of tinnitus in humans. This test relies on a phenomenon known as prepulse inhibition, whereby a startle response can be reduced in amplitude by placing a gap in a low-level, continuous background noise immediately prior to the startling stimulus. The hypothesis for this test is that if the background sound is adjusted to be similar to an animal’s tinnitus (induced artificially following noise exposure or drug administration), the tinnitus percept will fill in the gap and the startle response will not be reduced. The results from this first study indicated that using the Preyer reflex (a flexion of the pinnae in response to a startling stimulus) as this startle measure was more robust in guinea pigs than the commonly-used whole-body startle. Furthermore, transient tinnitus was reliably identified following salicylate administration. Following the development and validation of this test, a study was conducted to determine whether guinea pigs experienced tinnitus following unilateral noise exposure. Neural changes commonly associated with the condition (increases in spontaneous firing rates and changes in auditory brainstem responses) were examined, to determine whether there were any differences between animals that did develop tinnitus following noise exposure and those that did not. Two different methods were applied to the behavioural data to determine which animals were experiencing tinnitus. Regardless of the behavioural criteria used, increased spontaneous firing rates were observed in the inferior colliculus of noise-exposed guinea pigs, in comparison to control animals, but there were no differences between tinnitus and no-tinnitus animals. Conversely, significant reductions in the latency of components of the auditory brainstem response were present only in the tinnitus animals. The final study examined whether the original hypothesis for the behavioural test (that tinnitus is filling in the gap) was valid, or whether there was an alternative explanation for the deficits in behavioural gap detection observed previously, such as changes in the temporal acuity of the auditory system preventing detection of the gap. Recordings were made in the inferior colliculus of noise-exposed animals, separated into tinnitus and no-tinnitus groups according to the behavioural test, as well as unexposed control animals, to determine whether there were changes in the responses of single-units in detecting gaps of varying duration embedded in background noise. While some minor changes were present in no-tinnitus animals, tinnitus animals showed no significant changes in neural gap detection thresholds, demonstrating that changes in temporal acuity cannot account for behavioural gap detection deficits observed following noise exposure. Interestingly, significant shifts in the response types of cells were observed which did appear to relate to tinnitus. The present data indicate that the Preyer reflex gap detection test is appropriate for examining tinnitus in guinea pigs. It also suggests that increases in spontaneous firing rates at the level of the inferior colliculus cannot solely account for tinnitus. Changes in auditory brainstem responses, as well as shifts in response types, do appear to relate to tinnitus and warrant further investigation. |
