GLAST deficiency in mice exacerbates gap detection deficits in a model of salicylate-induced tinnitus
Gap detection or gap pre-pulse inhibition of the acoustic startle (GPIAS) has been successfully used in rat and guinea pig models of tinnitus, yet this system has proven to have low efficacy in CBA mice, with low basal GPIAS and subtle tinnitus like effects. Here, we tested five mouse strains (CBA,...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-08-01
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| Series: | Frontiers in Behavioral Neuroscience |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnbeh.2016.00158/full |
| _version_ | 1811345140859535360 |
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| author | Hong Yu Hong Yu Kim Vikhe Patil Chul Han Brian Fabella Barbara Canlon Shinichi Someya Christopher R. Cederroth |
| author_facet | Hong Yu Hong Yu Kim Vikhe Patil Chul Han Brian Fabella Barbara Canlon Shinichi Someya Christopher R. Cederroth |
| author_sort | Hong Yu |
| collection | DOAJ |
| description | Gap detection or gap pre-pulse inhibition of the acoustic startle (GPIAS) has been successfully used in rat and guinea pig models of tinnitus, yet this system has proven to have low efficacy in CBA mice, with low basal GPIAS and subtle tinnitus like effects. Here, we tested five mouse strains (CBA, BalbC, CD-1, C57BL/6 and sv129) for pre-pulse inhibition and gap detection with varying interstimulus intervals (ISI) and found the that mice from a CBA genetic background had the poorest capacities of suppressing the startle response in presence of a pre-pulse or a gap. CD-1 mice displayed variable responses throughout all ISI. Interestingly, C57BL/6, sv129 and BalbC showed efficient suppression with either pre-pulses or gaps with shorter ISI. The glutamate aspartate transporter (GLAST) is expressed in support cells from the cochlea and buffers the excess of glutamate. We hypothesized that loss of GLAST function could sensitize the ear to tinnitus-inducing agents, such as salicylate. Using shorter ISI to obtain a greater dynamic range to assess tinnitus-like effects, we found that disruption of gap detection by salicylate was exacerbated across various intensities of a 32 kHz narrow band noise gap carrier in GLAST KO mice when compared to their wild-type littermates. Auditory brainstem responses (ABR) and distortion products of otoacoustic emission (DPOAE) were performed to evaluate the effects on hearing functions. Salicylate caused greater auditory threshold shifts (near 15 dB) in GLAST KO mice than in wild-type mice across all tested frequencies, despite similarly reduced DPOAE. Despite these changes, inhibition using broad-band gap carriers and 32 kHz pre-pulses were not affected. Our study suggests that GLAST deficiency could become a useful experimental model to decipher the mechanisms underlying drug-induced tinnitus. Future studies addressing the neurological correlates of tinnitus in this model could provide additional insights into the mechanisms of tinnitus. |
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| format | Article |
| id | doaj.art-be36f73bd0974bb4bbcf42889698ea55 |
| institution | Directory Open Access Journal |
| issn | 1662-5153 |
| language | English |
| last_indexed | 2024-04-13T19:58:39Z |
| publishDate | 2016-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Behavioral Neuroscience |
| spelling | doaj.art-be36f73bd0974bb4bbcf42889698ea552022-12-22T02:32:16ZengFrontiers Media S.A.Frontiers in Behavioral Neuroscience1662-51532016-08-011010.3389/fnbeh.2016.00158202622GLAST deficiency in mice exacerbates gap detection deficits in a model of salicylate-induced tinnitusHong Yu0Hong Yu1Kim Vikhe Patil2Chul Han3Brian Fabella4Barbara Canlon5Shinichi Someya6Christopher R. Cederroth7Karolinska InstitutetFirst Hospital of JiLin UniversityKarolinska InstitutetUniversity of FloridaThe Rockefeller University and the Howard Hughes Medical InstituteKarolinska InstitutetUniversity of FloridaKarolinska InstitutetGap detection or gap pre-pulse inhibition of the acoustic startle (GPIAS) has been successfully used in rat and guinea pig models of tinnitus, yet this system has proven to have low efficacy in CBA mice, with low basal GPIAS and subtle tinnitus like effects. Here, we tested five mouse strains (CBA, BalbC, CD-1, C57BL/6 and sv129) for pre-pulse inhibition and gap detection with varying interstimulus intervals (ISI) and found the that mice from a CBA genetic background had the poorest capacities of suppressing the startle response in presence of a pre-pulse or a gap. CD-1 mice displayed variable responses throughout all ISI. Interestingly, C57BL/6, sv129 and BalbC showed efficient suppression with either pre-pulses or gaps with shorter ISI. The glutamate aspartate transporter (GLAST) is expressed in support cells from the cochlea and buffers the excess of glutamate. We hypothesized that loss of GLAST function could sensitize the ear to tinnitus-inducing agents, such as salicylate. Using shorter ISI to obtain a greater dynamic range to assess tinnitus-like effects, we found that disruption of gap detection by salicylate was exacerbated across various intensities of a 32 kHz narrow band noise gap carrier in GLAST KO mice when compared to their wild-type littermates. Auditory brainstem responses (ABR) and distortion products of otoacoustic emission (DPOAE) were performed to evaluate the effects on hearing functions. Salicylate caused greater auditory threshold shifts (near 15 dB) in GLAST KO mice than in wild-type mice across all tested frequencies, despite similarly reduced DPOAE. Despite these changes, inhibition using broad-band gap carriers and 32 kHz pre-pulses were not affected. Our study suggests that GLAST deficiency could become a useful experimental model to decipher the mechanisms underlying drug-induced tinnitus. Future studies addressing the neurological correlates of tinnitus in this model could provide additional insights into the mechanisms of tinnitus.http://journal.frontiersin.org/Journal/10.3389/fnbeh.2016.00158/fullHearing LossTinnitusMousegap detectionDisease Models, Animalstartle response |
| spellingShingle | Hong Yu Hong Yu Kim Vikhe Patil Chul Han Brian Fabella Barbara Canlon Shinichi Someya Christopher R. Cederroth GLAST deficiency in mice exacerbates gap detection deficits in a model of salicylate-induced tinnitus Frontiers in Behavioral Neuroscience Hearing Loss Tinnitus Mouse gap detection Disease Models, Animal startle response |
| title | GLAST deficiency in mice exacerbates gap detection deficits in a model of salicylate-induced tinnitus |
| title_full | GLAST deficiency in mice exacerbates gap detection deficits in a model of salicylate-induced tinnitus |
| title_fullStr | GLAST deficiency in mice exacerbates gap detection deficits in a model of salicylate-induced tinnitus |
| title_full_unstemmed | GLAST deficiency in mice exacerbates gap detection deficits in a model of salicylate-induced tinnitus |
| title_short | GLAST deficiency in mice exacerbates gap detection deficits in a model of salicylate-induced tinnitus |
| title_sort | glast deficiency in mice exacerbates gap detection deficits in a model of salicylate induced tinnitus |
| topic | Hearing Loss Tinnitus Mouse gap detection Disease Models, Animal startle response |
| url | http://journal.frontiersin.org/Journal/10.3389/fnbeh.2016.00158/full |
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