A behavioral paradigm to judge acute sodium salicylate-induced sound experience in rats: a new approach for an animal model on tinnitus

Rüttiger, Lukas; Ciuffani, Jürgen; Zenner, H. P.; Knipper, Marlies

doi:10.1016/s0378-5955(03)00075-3

Cited by 108 publications

(89 citation statements)

References 33 publications

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“…Sound exposure provides the best approximation of the chronic neurological changes that affect tinnitus patients but the induction process may take months to complete (Bauer et al, 1999;Longenecker et al, 2014). Acute salicylate treatment may be less representative of the clinical condition, but induction is rapid and more consistent (Rüttiger et al, 2003;Puel and Guitton, 2007;Stolzberg et al, 2012). Our study performed each method on separate groups of rats to illustrate the basic principles of the two approaches.…”

Section: Tinnitus Inductionmentioning

confidence: 99%

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Improving the Reliability of Tinnitus Screening in Laboratory Animals

Jones

May

2016

JARO

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Behavioral screening remains a contentious issue for animal studies of tinnitus. Most paradigms base a positive tinnitus test on an animal's natural tendency to respond to the Bsound^of tinnitus as if it were an actual sound. As a result, animals with tinnitus are expected to display soundconditioned behaviors when no sound is present or to miss gaps in background sounds because tinnitus Bfills in the gap.^Reliable confirmation of the behavioral indications of tinnitus can be problematic because the reinforcement contingencies of conventional discrimination tasks break down an animal's tendency to group tinnitus with sound. When responses in silence are rewarded, animals respond in silence regardless of their tinnitus status. When responses in silence are punished, animals stop responding. This study introduces stimulus classification as an alternative approach to tinnitus screening. Classification procedures train animals to respond to the common perceptual features that define a group of sounds (e.g., high pitch or narrow bandwidth). Our procedure trains animals to drink when they hear tinnitus and to suppress drinking when they hear other sounds. Animals with tinnitus are revealed by their tendency to drink in the presence of unreinforced probe sounds that share the perceptual features of the tinnitus classification. The advantages of this approach are illustrated by taking laboratory rats through a testing sequence that includes classification training, the experimental induction of tinnitus, and postinduction screening. Behavioral indications of tinnitus are interpreted and then verified by simulating a known tinnitus percept with objective sounds.

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Section: Tinnitus Inductionmentioning

confidence: 99%

“…The dose and timing of salicylate injections varies widely across prior studies (Jastreboff et al, 1988;Rüttiger et al, 2003;Yang et al, 2007;Radziwon et al, 2015). Our protocol was derived from preliminary assessments of commonly reported values.…”

Section: Tinnitus Inductionmentioning

confidence: 99%

Improving the Reliability of Tinnitus Screening in Laboratory Animals

Jones

May

2016

JARO

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“…The vast majority of these models have employed basic mechanisms of conditioning (Bauer et al 1999;Heffner and Harrington 2002;Guitton et al 2003;Rüttiger et al 2003;Lobarinas et al 2004;Heffner and Koay 2005). They typically require complex behavioral manipulations and weeks to months of animal training.…”

Section: Introductionmentioning

confidence: 99%

Development of Tinnitus in CBA/CaJ Mice Following Sound Exposure

Longenecker

Galazyuk

2011

JARO

109

140

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Tinnitus, the perception of a sound without an external acoustic source, is a complex perceptual phenomenon affecting the quality of life in 17% of the adult population. Despite its ubiquity and morbidity, the pathophysiology of tinnitus is a work in progress, and there is no generally accepted cure or treatment. Development of a reliable common animal model is crucial for tinnitus research and may advance this field. The goal of this study was to develop a tinnitus mouse model. Tinnitus was induced in an experimental group of mice by an exposure to a loud (116 dB sound pressure level (SPL)) narrow band noise (one octave, centered at 16 kHz) during 1 h under anesthesia. The tinnitus was then assessed behaviorally by measuring gap induced suppression of the acoustic startle reflex. We found that a vast majority of the sound-exposed mice (86%) developed behavioral signs of tinnitus. This was a complex, long lasting, and dynamic process. On the day following exposure, all mice demonstrated signs of acute tinnitus over the entire range of sound frequencies used for testing (10-31 kHz). However, 2-3 months later, a behavioral evidence of tinnitus was evident only at a narrow frequency range (20-31 kHz) representing a presumed chronic condition. Extracellular recordings confirmed a significantly higher rate of spontaneous activity in inferior colliculus neurons in sound-exposed compared to control mice. Surprisingly, unilateral sound exposure suppresses startle responses in mice and they remained suppressed even 3 months post-exposure, whereas auditory brainstem response thresholds were completely recovered during 2 months following exposure. In summary, behavioral evidence of tinnitus can be reliably developed in mice by sound exposure, and tinnitus induction can be assessed by quantifying prepulse inhibition of the acoustic startle reflex.

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“…Animal models of tinnitus have contributed significantly to the understanding of the pathophysiology of tinnitus (2)(3)(4)(5)(6)(7)(8). An emerging pattern associated with tinnitus pathology indicates that intense noise exposure leads to cochlear damage and hearing loss, which often is not clinically detected.…”

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confidence: 99%

Mice with behavioral evidence of tinnitus exhibit dorsal cochlear nucleus hyperactivity because of decreased GABAergic inhibition

Middleton

Kiritani

Pedersen

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

213

168

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Tinnitus has been associated with increased spontaneous and evoked activity, increased neural synchrony, and reorganization of tonotopic maps of auditory nuclei. However, the neurotransmitter systems mediating these changes are poorly understood. Here, we developed an in vitro assay that allows us to evaluate the roles of excitation and inhibition in determining the neural correlates of tinnitus. To measure the magnitude and spatial spread of evoked circuit activity, we used flavoprotein autofluorescence (FA) imaging, a metabolic indicator of neuronal activity. We measured FA responses after electrical stimulation of glutamatergic axons in slices containing the dorsal cochlear nucleus, an auditory brainstem nucleus hypothesized to be crucial in the triggering and modulation of tinnitus. FA imaging in dorsal cochlear nucleus brain slices from mice with behavioral evidence of tinnitus (tinnitus mice) revealed enhanced evoked FA response at the site of stimulation and enhanced spatial propagation of FA response to surrounding sites. Blockers of GABAergic inhibition enhanced FA response to a greater extent in control mice than in tinnitus mice. Blockers of excitation decreased FA response to a similar extent in tinnitus and control mice. These findings indicate that auditory circuits in mice with behavioral evidence of tinnitus respond to stimuli in a more robust and spatially distributed manner because of a decrease in GABAergic inhibition.T innitus, the persistent perception of a subjective sound in the absence of an acoustic stimulus (ringing of the ears), is often a debilitating condition that reduces the quality of life for many of those chronically affected. Estimates of the number of people experiencing tinnitus range from 8% to 20% of the general population (1). Despite the prevalence and growing incidence of tinnitus, the mechanisms underlying the induction and maintenance of tinnitus remain poorly understood.Animal models of tinnitus have contributed significantly to the understanding of the pathophysiology of tinnitus (2-8). An emerging pattern associated with tinnitus pathology indicates that intense noise exposure leads to cochlear damage and hearing loss, which often is not clinically detected. Decreased cochlear input leads to hyperactive, more responsive central auditory circuits, which is evidenced by functional MRI (fMRI) studies in patients with tinnitus and in vivo recordings in animal models of tinnitus (9-13). Increased spontaneous firing rates, increased evoked responses, and reorganization of tonotopic maps are consistent with decreased inhibition (disinhibition) (1, 14). However, direct evidence that disinhibition mediates these changes is still lacking. In addition, the alternative hypothesis that predicts increased excitation as a potential mechanism in mediating these changes has not been tested (15). Addressing these unexamined questions could lead to pharmacological approaches for treating tinnitus patients.We used flavoprotein autofluorescence (FA) imaging in brain slices prepared from...

show abstract

A behavioral paradigm to judge acute sodium salicylate-induced sound experience in rats: a new approach for an animal model on tinnitus

Cited by 108 publications

References 33 publications

Improving the Reliability of Tinnitus Screening in Laboratory Animals

Improving the Reliability of Tinnitus Screening in Laboratory Animals

Development of Tinnitus in CBA/CaJ Mice Following Sound Exposure

Mice with behavioral evidence of tinnitus exhibit dorsal cochlear nucleus hyperactivity because of decreased GABAergic inhibition

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