Characterization of the perceived sound of trauma-induced tinnitus in gerbils

Nowotny, Manuela; Remus, Martina; Kössl, Manfred; Gaese, Bernhard H.

doi:10.1121/1.3646902

Cited by 31 publications

(33 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Several recent studies have reported behavioral evidence of tinnitus in mice (26, 66, 75), rats (40), gerbils (76), and guinea pigs (34, 57) following noise exposure leading to temporary shifts in hearing thresholds. Tinnitus-like behavior was reported for the majority, but not all of the animals (26, 34, 40).…”

Section: Discussionmentioning

confidence: 99%

Non-Monotonic Relation between Noise Exposure Severity and Neuronal Hyperactivity in the Auditory Midbrain

Hesse¹,

Bakay²,

Ong³

et al. 2016

Front. Neurol.

View full text Add to dashboard Cite

The occurrence of tinnitus can be linked to hearing loss in the majority of cases, but there is nevertheless a large degree of unexplained heterogeneity in the relation between hearing loss and tinnitus. Part of the problem might be that hearing loss is usually quantified in terms of increased hearing thresholds, which only provides limited information about the underlying cochlear damage. Moreover, noise exposure that does not cause hearing threshold loss can still lead to “hidden hearing loss” (HHL), i.e., functional deafferentation of auditory nerve fibers (ANFs) through loss of synaptic ribbons in inner hair cells. While it is known that increased hearing thresholds can trigger increases in spontaneous neural activity in the central auditory system, i.e., a putative neural correlate of tinnitus, the central effects of HHL have not yet been investigated. Here, we exposed mice to octave-band noise at 100 and 105 dB SPL to generate HHL and permanent increases of hearing thresholds, respectively. Deafferentation of ANFs was confirmed through measurement of auditory brainstem responses and cochlear immunohistochemistry. Acute extracellular recordings from the auditory midbrain (inferior colliculus) demonstrated increases in spontaneous neuronal activity (a putative neural correlate of tinnitus) in both groups. Surprisingly, the increase in spontaneous activity was most pronounced in the mice with HHL, suggesting that the relation between hearing loss and neuronal hyperactivity might be more complex than currently understood. Our computational model indicated that these differences in neuronal hyperactivity could arise from different degrees of deafferentation of low-threshold ANFs in the two exposure groups. Our results demonstrate that HHL is sufficient to induce changes in central auditory processing, and they also indicate a non-monotonic relationship between cochlear damage and neuronal hyperactivity, suggesting an explanation for why tinnitus might occur without obvious hearing loss and conversely why hearing loss does not always lead to tinnitus.

show abstract

Section: Discussionmentioning

confidence: 99%

Non-Monotonic Relation between Noise Exposure Severity and Neuronal Hyperactivity in the Auditory Midbrain

Hesse¹,

Bakay²,

Ong³

et al. 2016

Front. Neurol.

View full text Add to dashboard Cite

show abstract

“…Since then a number of different laboratory animal species and various strains have been used for the behavioral assessment of tinnitus. Besides the laboratory rat ( Rattus norvegicus ) [8–51], these include the domestic house mouse ( Mus musculus ) [52–58], the chinchilla ( Chinchilla laniger ) [59, 60], the Syrian golden hamster ( Mesocricetus auratus ) [61–64], the guinea pig ( Cavia porcellus ) [65–67], and the Mongolian gerbil ( Meriones unguiculatus ) [68, 69]. Since the early studies by Jastreboff et al, the laboratory rat remains the most prominent species used for investigating tinnitus at the behavioral level.…”

Section: Species Used For Behavioral Testing Of Tinnitusmentioning

confidence: 99%

“…The second established method for inducing tinnitus in behavioral models is through acoustic trauma [8, 15, 20, 21, 23, 25–27, 30, 31, 37, 39–42, 46–49, 51–56, 59–66, 68, 69, 107]. It is assumed that a cochlear damage is in most cases the trigger for a sequence of events leading to the development of tinnitus in humans.…”

Section: Established Ways Of Tinnitus Induction In Animal Researchmentioning

confidence: 99%

“…In gerbils, a reliable and chronically induced tinnitus can be achieved by noise stimuli with an exposure time of at least 1 hour and narrow bandwidth leading to a temporary threshold shift and ultimately to self-sustaining activity perceived as phantom sound. Such a protocol leads to a hearing loss that disappears after 3 to 6 weeks and a tinnitus percept centered at the center-trauma frequency appearing 5 to 7 weeks after induction [68]. Hamsters exposed to a 10 kHz tone at 110 dB SPL for 4 h exhibited tinnitus symptoms within one day after exposure [62] indicating the possibility of an almost immediately tinnitus onset after acoustic trauma.…”

Section: Established Ways Of Tinnitus Induction In Animal Researchmentioning

confidence: 99%

“…This paradigm or some derivatives (e.g., measuring the Preyer reflex in guinea pigs by Berger et al [67]) were adopted by many research groups [11, 20, 23, 46, 48, 49, 52, 53, 64, 65, 68, 69] because they offer a number of advantages. The main benefit for experimentalists is that it is a fast method in terms of training and testing.…”

Section: Behavioral Models For Assessing Tinnitus In Animalsmentioning

confidence: 99%

See 2 more Smart Citations

Animal Models of Subjective Tinnitus

Behrens

2014

Neural Plasticity

View full text Add to dashboard Cite

Tinnitus is one of the major audiological diseases, affecting a significant portion of the ageing society. Despite its huge personal and presumed economic impact there are only limited therapeutic options available. The reason for this deficiency lies in the very nature of the disease as it is deeply connected to elementary plasticity of auditory processing in the central nervous system. Understanding these mechanisms is essential for developing a therapy that reverses the plastic changes underlying the pathogenesis of tinnitus. This requires experiments that address individual neurons and small networks, something usually not feasible in human patients. However, in animals such invasive experiments on the level of single neurons with high spatial and temporal resolution are possible. Therefore, animal models are a very critical element in the combined efforts for engineering new therapies. This review provides an overview over the most important features of animal models of tinnitus: which laboratory species are suitable, how to induce tinnitus, and how to characterize the perceived tinnitus by behavioral means. In particular, these aspects of tinnitus animal models are discussed in the light of transferability to the human patients.

show abstract

A Novel Organ of Corti Explant Model for the Study of Cochlear Implantation Trauma

Bas¹,

Gupta²,

Water³

2012

The Anatomical Record

View full text Add to dashboard Cite

This study presents a novel in vitro model of electrode insertion trauma-induced hair cell (HC) damage and loss and its application for testing the efficacy of otoprotective drugs. In the cochlear implant (CI) procedure as a treatment for profound deafness, an electrode array is surgically inserted to provide electrical stimulation to the auditory nerve. Mechanical trauma from insertion of a CI electrode into the scala tympani can lead to inflammation and a high level of oxidative stress, which can initiate the apoptosis of auditory HCs and intracochlear fibrosis. HC apoptosis and intracochlear fibrosis are thought to be causes of poor CI functional outcomes. In order to gain insight into the molecular mechanisms that initiate HC apoptosis and scala tympani fibrosis following electrode insertion trauma (EIT), and the otoprotective effects of dexamethasone (DXM) observed in previous studies, an in vitro model of EIT was designed. Here we present and characterize a novel, reproducible in vitro model for the study of cellular and molecular events that occur following an EIT procedure. Cochleae from 3-day-old rats were subjected to a cochleostomy and were then divided into three groups: (1) control, (2) EIT, and (3) EIT þ DXM (20 lg/mL). In Groups 2 and 3, a 0.28-mm diameter monofilament fishing line was introduced through the small cochleostomy located next to the round window area, allowing for an insertion of between 110 and 150 . HC counts, gene expression for pro-inflammatory cytokines (i.e., TNFa and IL-1b), pro-inflammatory inducible enzymes (i.e., iNOS and COX-2) and growth factors (i.e., TGFb1, TGFb3 and CTGF), oxidative stress (i.e., Cell-ROX), and analyses of apoptosis pathways (i.e., caspase-3, apoptosis induced factor and Endonuclease G) were carried out on all explants at different time points. The results of this EIT in vitro model show the initiation of wound healing in which an inflammatory response is followed by a proliferative-fibrosis phase. Moreover, DXM treatment of EIT explants inhibited the inflammatory response and promoted a nonscarring wound healing process. The novel in vitro model described here will improve our understanding of mechanisms underlying CI insertion trauma and protective strategies such as DXM treatment.

show abstract

Characterization of the perceived sound of trauma-induced tinnitus in gerbils

Cited by 31 publications

References 46 publications

Non-Monotonic Relation between Noise Exposure Severity and Neuronal Hyperactivity in the Auditory Midbrain

Non-Monotonic Relation between Noise Exposure Severity and Neuronal Hyperactivity in the Auditory Midbrain

Animal Models of Subjective Tinnitus

A Novel Organ of Corti Explant Model for the Study of Cochlear Implantation Trauma

Contact Info

Product

Resources

About