Salicylate induced tinnitus: Behavioral measures and neural activity in auditory cortex of awake rats

Yang, Guang; Lobariñas, Edward; Zhang, Liyan; Turner, Jeremy G.; Stolzberg, Daniel; Salvi, Richard; Sun, Wei

doi:10.1016/j.heares.2006.06.013

Cited by 218 publications

(246 citation statements)

References 43 publications

(67 reference statements)

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“…Deafferentation and tinnitus models show increased spontaneous activity, peak spike rates within bursts, and rhythmicity of spiking in IC neurons (Bauer et al, 2008). Tinnitus-related downregulation of inhibition in the AI is thought to involve cortical receptive field reorganization, and cortical hyperactivity and bursting (Mühlnickel et al, 1998;Lanting et al, 2009;Yang et al, 2011;.…”

Section: Discussionmentioning

confidence: 99%

“…It modulates input/output functions, alters frequency tuning, and sharpens temporal response accuracy while gating neurotransmission to primary auditory cortex (AI; Wang et al, 2008;Edeline, 2011;Richardson et al, 2012). Downregulation of inhibitory function has been suggested to underpin tinnitus pathology in dorsal cochlear nucleus (DCN; Wang et al, 2009;Pilati et al, 2012a;Pilati et al, 2012b), inferior colliculus (IC; Bauer et al, 2008;Dong et al, 2009), and AI (Noreña and Eggermont, 2003;Yang et al, 2007Yang et al, , 2011 where tinnitus is accompanied by increased spontaneous activity, bursting, enhanced sound-evoked responses, and reduction in markers of inhibitory neurotransmission (Eggermont and Roberts, 2004;Middleton et al, 2011). This downregulation of inhibitory function is thought to reflect altered homeostatic plasticity compensating for the loss of peripheral excitatory drive (Noreña, 2011;Richardson et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Enhanced GABAA-Mediated Tonic Inhibition in Auditory Thalamus of Rats with Behavioral Evidence of Tinnitus

Sametsky

Turner

Larsen

et al. 2015

Journal of Neuroscience

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in vitro, using the following three groups of adult rats: unexposed control (Ctrl); sound exposed with behavioral evidence of tinnitus (Tin); and sound exposed with no behavioral evidence of tinnitus (Non-T). Tonic GABA A R currents were evoked using the selective agonist gaboxadol. Months after a tinnitus-inducing sound exposure, gaboxadol-evoked tonic GABA A R currents showed significant tinnitus-related increases contralateral to the sound exposure. In situ hybridization studies found increased mRNA levels for GABA A R ␦-subunits contralateral to the sound exposure. Tin rats showed significant increases in the number of spikes per burst evoked using suprathreshold-injected current steps. In summary, we found little evidence of tinnitus-related decreases in GABAergic neurotransmission. Tinnitus and chronic pain may reflect thalamocortical dysrhythmia, which results from abnormal theta-range resonant interactions between thalamus and cortex, due to neuronal hyperpolarization and the initiation of low-threshold calcium spike bursts (Walton and Llinás, 2010). In agreement with this hypothesis, we found tinnitus-related increases in tonic extrasynaptic GABA A R currents, in action potentials/evoked bursts, and in GABA A R ␦-subunit gene expression. These tinnitus-related changes in GABAergic function may be markers for tinnitus pathology in the MGB.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Enhanced GABAA-Mediated Tonic Inhibition in Auditory Thalamus of Rats with Behavioral Evidence of Tinnitus

Sametsky

Turner

Larsen

et al. 2015

Journal of Neuroscience

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“…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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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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“…Methods in the animal laboratory include gap pre-pulse inhibition of acoustic startle (Yang et al, 2007), schedule-induced polidypsia avoidance conditioning (Lobarinas et al, 2004;Yang et al, 2007), active avoidance (Guitton et al, 2003) and conditioned suppression and avoidance (Jastreboff and Sasaki, 1994). While some conditioning paradigms can provide estimates of pitch and loudness (Jastreboff and Sasaki, 1994), a complete characterisation of the perceptual and psychological attributes of TI cannot be established in laboratory animals.…”

Section: Guiding Principles From Animal Studiesmentioning

confidence: 99%

The mechanisms of tinnitus: Perspectives from human functional neuroimaging

2009

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In this review, we highlight the contribution of advances in human neuroimaging to the current understanding of central mechanisms underpinning tinnitus and explain how interpretations of neuroimaging data have been guided by animal models. The primary motivation for studying the neural subtrates of tinnitus in humans has been to demonstrate objectively its representation in the central auditory system and to develop a better understanding of its diverse pathophysiology and of the functional interplay between sensory, cognitive and affective systems. The ultimate goal of neuroimaging is to identify subtypes of tinnitus in order to better inform treatment strategies. The three neural mechanisms considered in this review may provide a basis for TI classification. While human neuroimaging evidence strongly implicates the central auditory system and emotional centres in TI, evidence for the precise contribution from the three mechanisms is unclear because the data are somewhat inconsistent. We consider a number of methodological issues limiting the field of human neuroimaging and recommend approaches to overcome potential inconsistency in results arising from poorly matched participants, lack of appropriate controls and low statistical power. AbstractIn this review, we highlight the contribution of advances in human neuroimaging to the current understanding of central mechanisms underpinning tinnitus and explain how interpretations of neuroimaging data have been guided by animal models. The primary motivation for studying the neural subtrates of tinnitus in humans has been to demonstrate objectively its representation in the central auditory system and to develop a better understanding of its diverse pathophysiology and of the functional interplay between sensory, cognitive and affective systems. The ultimate goal of neuroimaging is to identify subtypes of tinnitus in order to better inform treatment strategies. The three neural mechanisms considered in this review may provide a basis for TI classification. While human neuroimaging evidence strongly implicates the central auditory system and emotional centres in TI, evidence for the precise contribution from the three mechanisms is unclear because the data are somewhat inconsistent. We consider a number of methodological issues limiting the field of human neuroimaging and recommend approaches to overcome potential inconsistency in results arising from poorly matched participants, lack of appropriate controls and low statistical power.

show abstract

Salicylate induced tinnitus: Behavioral measures and neural activity in auditory cortex of awake rats

Cited by 218 publications

References 43 publications

Enhanced GABAA-Mediated Tonic Inhibition in Auditory Thalamus of Rats with Behavioral Evidence of Tinnitus

Enhanced GABAA-Mediated Tonic Inhibition in Auditory Thalamus of Rats with Behavioral Evidence of Tinnitus

Improving the Reliability of Tinnitus Screening in Laboratory Animals

The mechanisms of tinnitus: Perspectives from human functional neuroimaging

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