Selective Impairment in Frequency Discrimination in a Mouse Model of Tinnitus

Abstract

Tinnitus is an auditory disorder, which affects millions of Americans, including active duty service members and veterans. It is manifested by a phantom sound that is commonly restricted to a specific frequency range. Because tinnitus is associated with hearing deficits, understanding how tinnitus affects hearing perception is important for guiding therapies to improve the quality of life in this vast group of patients. In a rodent model of tinnitus, prolonged exposure to a tone leads to a selective decrease in gap detection in specific frequency bands. However, whether and how hearing acuity is affected for sounds within and outside those frequency bands is not well understood. We induced tinnitus in mice by prolonged exposure to a loud mid-range tone, and behaviorally assayed whether mice exhibited a change in frequency discrimination acuity for tones embedded within the mid-frequency range and high-frequency range at 1, 4, and 8 weeks post-exposure. A subset of tone-exposed mice exhibited tinnitus-like symptoms, as demonstrated by selective deficits in gap detection, which were restricted to the high frequency range. These mice exhibited impaired frequency discrimination both for tones in the mid-frequency range and high-frequency range. The remaining tone exposed mice, which did not demonstrate behavioral evidence of tinnitus, showed temporary deficits in frequency discrimination for tones in the mid-frequency range, while control mice remained unimpaired. Our findings reveal that the high frequency-specific deficits in gap detection, indicative of tinnitus, are associated with impairments in frequency discrimination at the frequency of the presumed tinnitus.

Changes in spontaneous movement in response to silent gaps are not robust enough to indicate the perception of tinnitus in mice

“…As expected, when comparing within click or test frequencies, sham exposure caused minimal (non-significant) changes in thresholds shifts (white bars in Fig 2 , Table 1 ), whereas noise exposure caused significant increases in threshold shifts (gray bars in Fig 2 , Table 1 ) at 16 and 32 kHz (Mann Whitney rank comparison test). This noise exposure paradigm and the resulting threshold shifts are consistent with the induction of tinnitus as described in other studies examining tinnitus in mouse models [ 16 , 17 , 20 ]. In our experiments, mice were noised under anesthesia with ketamine.…”

“…We also wanted to examine whether noise exposure caused changes more generally in activity (and thereby test our third prediction). For these experiments mice were divided into two groups, one undergoing sham noise exposure and a second undergoing noise exposure (as described in the Methods ) consistent with the induction of tinnitus [ 16 , 17 , 20 ]. These two groups of mice underwent a third trial of movement monitoring identical to that used for trials 1 and 2.…”

“…For example, tinnitus has been induced in CBA/CaJ anesthetized with ketamine/xylazine and exposed to noise centered at 16 kHz (116 dB SPL) for 1 h [ 9 ]. In awake CBA/J mice, tinnitus has been induced by exposure to noise centered at 10 kHz (120 dB SPL) for 1 h [ 16 ]. Finally, in C57BL/6J mice tinnitus was induced by exposure to noise centered at 16 kHz (116 dB SPL) for 1 h following anesthesia with isoflurane [ 17 ].…”

Therapeutic Value of Ginkgo biloba Extract EGb 761® in an Animal Model (Meriones unguiculatus) for Noise Trauma Induced Hearing Loss and Tinnitus

“…The PPI modulated ASR paradigm is used to assess the potential existence of a tinnitus percept [ 32 , 33 ]. It consists of a 105 dB SPL pure tone startle stimulus of 1 kHz, 2 kHz, 4 kHz, 8 kHz or 16 kHz within a 50 dB SPL continuous white noise, a silent 15 ms gap within the noise 100 ms before the startle stimulus served in half of the trials as pre-pulse.…”

Gain Control in the Auditory Cortex Evoked by Changing Temporal Correlation of Sounds

“…The rat was implanted with an electrode microdrive and was trained to sit still in the recording chamber. Animals were monitored via video recording for their level of arousal, following methods previously developed in the laboratory (Aizenberg and Geffen 2013;Carruthers et al 2013;Aizenberg et al 2015;Blackwell et al 2015;Carruthers et al 2015;Mwilambwe-Tshilobo et al 2015). The chronically implanted microdrive was connected via a cable to the Neuralynx digital acquisition system.…”