The blinking eye as a window into tinnitus: A new animal model of tinnitus in the macaque

Rogenmoser, Lars; Kuśmierek, Paweł; Archakov, Denis; Rauschecker, Josef P.

doi:10.1016/j.heares.2022.108517

Cited by 4 publications

(6 citation statements)

References 105 publications

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“…In addition to the commonly used rodent animal models, salicylate-induced tinnitus studies have also been conducted in non-rodent animals. For instance, in monkeys administered salicylate orally, tinnitus-like behaviors and altered neural activity in the auditory cortex were observed, consistent with findings in rodent models ( Rogenmoser et al, 2022 ). Similarly, cats receiving intraperitoneal salicylate injection exhibited increased spontaneous neural activity in the auditory system ( Ochi and Eggermont, 1996 ; Eggermont and Kenmochi, 1998 ; Eggermont, 2008 ).…”

Section: Introductionsupporting

confidence: 83%

“…Tinnitus, similar in quality to the background noise, “fills in” the gap and reduces inhibition. However, it is essential to note that GPIAS relies considerably on the individual’s hearing level, and caution should be exercised when studying subjects with hearing loss ( Galazyuk and Hebert, 2015 ; Rogenmoser et al, 2022 ). Various behavioral training methods such as conditioned level or lick suppression ( Ruel et al, 2008 ; Wang et al, 2019 ), place preference ( Yang et al, 2011 ), two-alternative choice ( Stolzberg et al, 2013 ), and tactile reflex ( Rogenmoser et al, 2022 ) have been utilized to screen tinnitus-like behaviors accurately.…”

Section: Discussionmentioning

confidence: 99%

“…Firstly, salicylate also induces hearing loss, which may compromise the verification of tinnitus-like behavior through the GPIAS protocol that relies on auditory perception. Therefore, there is a need to develop more reliable behavioral protocols for validating salicylate-induced tinnitus behaviors ( Galazyuk and Hebert, 2015 ; Rogenmoser et al, 2022 ). Secondly, we only verified salicylate-induced tinnitus-like behavior in wild-type mice and did not assess this in Gad2-Cre mice, in which the modulatory effects of aTRN on tinnitus were examined in the current study ( Masri et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

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Characterization of the neural circuitry of the auditory thalamic reticular nucleus and its potential role in salicylate-induced tinnitus

Dai,

Qu,

Shen

et al. 2024

Front. Neurosci.

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IntroductionSubjective tinnitus, the perception of sound without an external acoustic source, is often subsequent to noise-induced hearing loss or ototoxic medications. The condition is believed to result from neuroplastic alterations in the auditory centers, characterized by heightened spontaneous neural activities and increased synchrony due to an imbalance between excitation and inhibition. However, the role of the thalamic reticular nucleus (TRN), a structure composed exclusively of GABAergic neurons involved in thalamocortical oscillations, in the pathogenesis of tinnitus remains largely unexplored.MethodsWe induced tinnitus in mice using sodium salicylate and assessed tinnitus-like behaviors using the Gap Pre-Pulse Inhibition of the Acoustic Startle (GPIAS) paradigm. We utilized combined viral tracing techniques to identify the neural circuitry involved and employed immunofluorescence and confocal imaging to determine cell types and activated neurons.ResultsSalicylate-treated mice exhibited tinnitus-like behaviors. Our tracing clearly delineated the inputs and outputs of the auditory-specific TRN. We discovered that chemogenetic activation of the auditory TRN significantly reduced the salicylate-evoked rise in c-Fos expression in the auditory cortex.DiscussionThis finding posits the TRN as a potential modulatory target for tinnitus treatment. Furthermore, the mapped sensory inputs to the auditory TRN suggest possibilities for employing optogenetic or sensory stimulations to manipulate thalamocortical activities. The precise mapping of the auditory TRN-mediated neural pathways offers a promising avenue for designing targeted interventions to alleviate tinnitus symptoms.

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Section: Introductionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Characterization of the neural circuitry of the auditory thalamic reticular nucleus and its potential role in salicylate-induced tinnitus

Dai,

Qu,

Shen

et al. 2024

Front. Neurosci.

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“…The pig is the closest species to humans in evolution except for primates, and the structure of its auditory organ is highly similar to that of humans, which makes the pig very suitable for the model of auditory studies [ 181 ]. As a non-human primate, rhesus macaque is commonly used to study sensory and perceptual processing [ 182 ]. However, these larger mammalian models (pig and rhesus macaque) bear inter-species differences to their human counterparts, which may compromise the relevance of the gathered data [ 177 ].…”

Section: Crispr/cas9 In Genetic Hearing Lossmentioning

confidence: 99%

The applications of CRISPR/Cas-mediated genome editing in genetic hearing loss

Tao

Deng

et al. 2023

Cell Biosci

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Hearing loss (HL) can be caused by a number of different genetic factors. Non-syndromic HL refers that HL occurs as an isolated symptom in an individual, whereas syndromic HL refers that HL is associated with other symptoms or abnormalities. To date, more than 140 genes have been identified as being associated with non-syndromic HL, and approximately 400 genetic syndromes can include HL as one of the clinical symptoms. However, no gene therapeutic approaches are currently available to restore or improve hearing. Therefore, there is an urgent necessity to elucidate the possible pathogenesis of specific mutations in HL-associated genes and to investigate the promising therapeutic strategies for genetic HL. The development of the CRISPR/Cas system has revolutionized the field of genome engineering, which has become an efficacious and cost-effective tool to foster genetic HL research. Moreover, several in vivo studies have demonstrated the therapeutic efficacy of the CRISPR/Cas-mediated treatments for specific genetic HL. In this review, we briefly introduce the progress in CRISPR/Cas technique as well as the understanding of genetic HL, and then we detail the recent achievements of CRISPR/Cas technique in disease modeling and therapeutic strategies for genetic HL. Furthermore, we discuss the challenges for the application of CRISPR/Cas technique in future clinical treatments.

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“…Research in mice, rats, and guinea pigs demonstrated that enhanced excitability could not be found in every animal, restricting the assumption of hyperexcitability as the only underlying mechanism for tinnitus (see, e.g., [ 51 – 53 ]). Next to extensive research on rodents or cats [ 158 ], research on primates additionally allows to investigate the role of the frontal cortex in tinnitus [ 159 ]. Animal models comprise concepts of cellular, molecular, or pathophysiological features that cannot be derived from human subjects [ 158 ] since they allow for invasive procedures.…”

Section: Shortcomings and Problems Of The Fieldmentioning

confidence: 99%

Eavesdropping on Tinnitus Using MEG: Lessons Learned and Future Perspectives

Reisinger,

Demarchi,

Weisz

2023

JARO

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Tinnitus has been widely investigated in order to draw conclusions about the underlying causes and altered neural activity in various brain regions. Existing studies have based their work on different tinnitus frameworks, ranging from a more local perspective on the auditory cortex to the inclusion of broader networks and various approaches towards tinnitus perception and distress. Magnetoencephalography (MEG) provides a powerful tool for efficiently investigating tinnitus and aberrant neural activity both spatially and temporally. However, results are inconclusive, and studies are rarely mapped to theoretical frameworks. The purpose of this review was to firstly introduce MEG to interested researchers and secondly provide a synopsis of the current state. We divided recent tinnitus research in MEG into study designs using resting state measurements and studies implementing tone stimulation paradigms. The studies were categorized based on their theoretical foundation, and we outlined shortcomings as well as inconsistencies within the different approaches. Finally, we provided future perspectives on how to benefit more efficiently from the enormous potential of MEG. We suggested novel approaches from a theoretical, conceptual, and methodological point of view to allow future research to obtain a more comprehensive understanding of tinnitus and its underlying processes.

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The blinking eye as a window into tinnitus: A new animal model of tinnitus in the macaque

Cited by 4 publications

References 105 publications

Characterization of the neural circuitry of the auditory thalamic reticular nucleus and its potential role in salicylate-induced tinnitus

Characterization of the neural circuitry of the auditory thalamic reticular nucleus and its potential role in salicylate-induced tinnitus

The applications of CRISPR/Cas-mediated genome editing in genetic hearing loss

Eavesdropping on Tinnitus Using MEG: Lessons Learned and Future Perspectives

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