Tinnitus, a subjective perception of a phantom auditory sensation (e.g., ringing in the ears), affects approximately 10-15% of the general population. At present, there is no cure, and there are no drugs known that suppress the disorder. Tinnitus, in its chronic form, is most often associated with noise-induced hearing loss. Although the underlying mechanism(s) of tinnitus remain elusive, it is well established that hearing loss alters the balance of excitation and inhibition throughout the central auditory pathway, ultimately leading to cortical plasticity. Examples of cortical plasticity observed in animal models include a reorganization of the tonotopic map following a frequency-specific cochlear lesion (i.e., intramodal cortical plasticity), and in the case of profound deafness caused by ototoxicity, neurons in the auditory cortex becoming responsive to somatosensory stimulation (i.e., crossmodal cortical plasticity). It has been proposed that tinnitus emerges as a negative consequence of intramodal cortical plasticity following hearing loss;however, the intramodal cortical plasticity theory of tinnitus has not been investigated thoroughly as no studies have performed both cortical electrophysiological recordings and a behavioral assessment of tinnitus in the same animals. Furthermore, given that approximately two-thirds of human patients suffering from tinnitus can modulate its pitch and loudness by somatosensory stimulation of their head and neck (termed """"""""somatic tinnitus""""""""), it is reasonable to predict that, in addition to tonotopic map reorganization, crossmodal cortical plasticity may be involved in the disorder. Thus, this proposal will investigate, for the first time, the relationship between chronic tinnitus and auditory cortex plasticity (intra- and crossmodal) caused by noise-induced hearing loss. To that end, electrophysiological recording will be used to assess the responsiveness of neurons in the primary auditory cortex of adult rats to auditory and somatosensory stimulation 45 days after monaural exposure to high- frequency noise. To determine which noise-exposed rats develop chronic tinnitus, behavioral testing with a gap pre-pulse inhibition acoustic startle paradigm will be used, and the results will be correlated with the electrophysiological findings. It is hypothesized that only a subset of noise-exposed rats will show both intra- and crossmodal cortical plasticity and that such changes correlate with behavioral evidence of tinnitus. Moreover, it is predicted that the crossmodal cortical plasticity will be characterized by neurons that respond to somatosensory stimulation of the rostral body surface (i.e., head and neck). A second series of experiments will determine if cortical plasticity and behavioral evidence of tinnitus can be suppressed by housing rats in an acoustically-enriched environment for one month. The rationale for this rehabilitation is based on recent studies on hearing-impaired animals and humans which suggest that intramodal cortical plasticity can be offset by chronic acoustic stimulation at the specific frequencies associated with the hearing loss. The efficacy of this treatment approach (sound therapy) has not been evaluated using animals with behavioral evidence of tinnitus.
Tinnitus, a subjective perception of a phantom auditory sensation (e.g., ringing in the ears), affects approximately 10-15% of the general population. Using an animal model in which tinnitus and hearing loss are induced by extremely loud noise, this proposal will determine if tinnitus results from intramodal and/or crossmodal plasticity in the auditory cortex induced by monaural hearing loss, and whether an enriched acoustic environment can suppress tinnitus by reversing the noise-induced cortical plasticity.
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