Decreasing dorsal cochlear nucleus activity ameliorates noise-induced tinnitus perception in mice
| dc.contributor.author | Borges, Thawann Malfatti | |
| dc.contributor.author | Boerner, Barbara Ciralli | |
| dc.contributor.author | Hilscher, Markus M. | |
| dc.contributor.author | Leao, Richardson Naves | |
| dc.contributor.author | Leão, Emelie Katarina Svahn | |
| dc.date.accessioned | 2022-05-18T18:44:50Z | |
| dc.date.available | 2022-05-18T18:44:50Z | |
| dc.date.issued | 2022-05-12 | |
| dc.description.resumo | Background: The dorsal cochlear nucleus (DCN) is a region known to integrate somatosensory and auditory inputs and is identified as a potential key structure in the generation of phantom sound perception, especially noise-induced tinnitus. Yet, how altered homeostatic plasticity of the DCN induces and maintains the sensation of tinnitus is not clear. Here, we chemogenetically decrease activity of a subgroup of DCN neurons, Ca2+/Calmodulin kinase 2 α (CaMKII α)-positive DCN neurons, using Gi-coupled human M4 Designer Receptors Exclusively Activated by Designer Drugs (hM4Di DREADDs), to investigate their role in noise-induced tinnitus. Results: Mice were exposed to loud noise (9–11kHz, 90dBSPL, 1h, followed by 2h of silence), and auditory brainstem responses (ABRs) and gap prepulse inhibition of acoustic startle (GPIAS) were recorded 2 days before and 2 weeks after noise exposure to identify animals with a significantly decreased inhibition of startle, indicating tinnitus but without permanent hearing loss. Neuronal activity of CaMKII α+ neurons expressing hM4Di in the DCN was lowered by administration of clozapine-N-oxide (CNO). We found that acutely decreasing firing rate of CaMKII α+ DCN units decrease tinnitus-like responses (p = 3e −3, n = 11 mice), compared to the control group that showed no improvement in GPIAS (control virus; CaMKII α-YFP + CNO, p = 0.696, n = 7 mice). Extracellular recordings confirmed CNO to decrease unit firing frequency of CaMKII α-hM4Di+ mice and alter best frequency and tuning width of response to sound. However, these effects were not seen if CNO had been previously administered during the noise exposure (n = 6 experimental and 6 control mice). Conclusion: We found that lowering DCN activity in mice displaying tinnitus-related behavior reduces tinnitus, but lowering DCN activity during noise exposure does not prevent noise-induced tinnitus. Our results suggest that CaMKII α-positive cells in the DCN are not crucial for tinnitus induction but play a significant role in maintaining tinnitus perception in mice | pt_BR |
| dc.identifier.citation | MALFATTI, Thawann; CIRALLI, Barbara; HILSCHER, Markus M.; LEAO, Richardson N.; LEAO, Katarina E. Decreasing dorsal cochlear nucleus activity ameliorates noise-induced tinnitus perception in mice. Bmc Biology, [S. l.], v. 20, p. 102, maio 2022. Doi: http://dx.doi.org/10.1186/s12915-022-01288-1. Disponível em: https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-022-01288-1. Acesso em: 18 maio 2022. | pt_BR |
| dc.identifier.doi | https://doi.org/10.1186/s12915-022-01288-1 | |
| dc.identifier.uri | https://repositorio.ufrn.br/handle/123456789/47208 | |
| dc.language | en | pt_BR |
| dc.publisher | Springer Science and Business Media LLC | pt_BR |
| dc.rights | Attribution 3.0 Brazil | * |
| dc.rights.uri | http://creativecommons.org/licenses/by/3.0/br/ | * |
| dc.subject | Tinnitus | pt_BR |
| dc.subject | Dorsal cochlear nucleus | pt_BR |
| dc.subject | Chemogenetics | pt_BR |
| dc.subject | Unit recording | pt_BR |
| dc.subject | Gap Prepulse Inhibition of Acoustic Startle (GPIAS) ( | pt_BR |
| dc.title | Decreasing dorsal cochlear nucleus activity ameliorates noise-induced tinnitus perception in mice | pt_BR |
| dc.type | article | pt_BR |
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