Abstract
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 “sound” of tinnitus as if it were an actual sound. As a result, animals with tinnitus are expected to display sound-conditioned behaviors when no sound is present or to miss gaps in background sounds because tinnitus “fills 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.
Similar content being viewed by others
References
Allman BL, Baizer JS, Salvi RJ, Lobarinas E (2013) Special issue in hearing research: neuroscience of tinnitus. Hear Res 295:1–2
Bauer CA, Brozoski TJ, Rojas R, Boley J, Wyder M (1999) Behavioral model of chronic tinnitus in rats. Otolaryngol Head Neck Surg 121:457–462
Beecher MD, Petersen MR, Zoloth SR, Moody DB, Stebbins WC (1979) Perception of conspecific vocalizations by Japanese macaques. Evidence for selective attention and neural lateralization. Brain Behav Evol 16:443–460
Berger JI, Coomber B, Shackleton TM, Palmer AR, Wallace MN (2013) A novel behavioural approach to detecting tinnitus in the Guinea pig. J Neurosci Methods 213:188–195
Boyen K, Baskent D, van Dijk P (2015) The gap detection test: can it Be used to diagnose tinnitus? Ear Hear 36:e138–e145
Brennan JF, Jastreboff PJ (1991) Generalization of conditioned suppression during salicylate -induced phantom auditory perception in rats. Acta Neurobiol Exp 51:15–27
Brozoski TJ, Bauer CA (2016) Animal models of tinnitus. Hear Res 338:88–97
Campolo J, Lobarinas E, Salvi R (2013) Does tinnitus “fill in” the silent gaps? Noise Health 15:398–405
Cazals Y (2000) Auditory sensori-neural alterations induced by salicylate. Prog Neurobiol 62:583–631
Chao Z, Qiuju W, Wei S (2014) Animal behavioral models of tinnitus. J Otol 9:58–63
Eggermont JJ, Roberts LE (2015) Tinnitus: animal models and findings in humans. Cell Tissue Res 361:311–336
Fournier P, Hebert S (2013) Gap detection deficits in humans with tinnitus as assessed with the acoustic startle paradigm: does tinnitus fill in the gap? Hear Res 295:16–23
Galazyuk A, Hebert S (2015) Gap-prepulse inhibition of the acoustic startle reflex (GPIAS) for tinnitus assessment: current status and future directions. Front Neurol 6:88
Heffner HE, Heffner RS (1995) Conditioned avoidance. In: Klump GM, Dooling RJ, Fay RR, Stebbins WC (eds) Methods in comparative psychoacoustics. Birkhauser Verlag, Basel, pp. 79–94
Heffner HE, Harrington IA (2002) Tinnitus in hamsters following exposure to intense sound. Hear Res 170:83–95
Heffner HE, Koay G, Hill EM, Heffner RS (2013) Conditioned suppression/avoidance as a procedure for testing hearing in birds: the domestic pigeon (Columba livia). Behav Res Methods 45:383–392
Hickox AE, Liberman MC (2014) Is noise-induced cochlear neuropathy key to the generation of hyperacusis or tinnitus? J Neurophysiol 111:552–564
Hu SS, Mei L, Chen JY, Huang ZW, Wu H (2014) Expression of immediate-early genes in the inferior colliculus and auditory cortex in salicylate-induced tinnitus in rat. Eur J Histochem: EJH 58:2294
Jastreboff PJ, Sasaki CT (1994) An animal model for tinnitus: a decade of development. Otol Neurotol 15:19–27
Jastreboff PJ, Sasaki CT, Brennan JF (1988) An animal model for tinnitus. Laryngoscope 98:280–286
Kaltenbach JA, Zacharek MA, Zhang J, Frederick S (2004) Activity in the dorsal cochlear nucleus of hamsters previously tested for tinnitus following intense tone exposure. Neurosci Lett 355:121–125
Lauer AM, May BJ, Hao ZJ, Watson J (2009) Analysis of environmental sound levels in modern rodent housing rooms. Lab Anim (NY) 38:154–160
Lobarinas E, Hayes SH, Allman BL (2013) The gap-startle paradigm for tinnitus screening in animal models: limitations and optimization. Hear Res 295:150–160
Lobarinas E, Sun W, Cushing R, Salvi R (2004) A novel behavioral paradigm for assessing tinnitus using schedule-induced polydipsia avoidance conditioning (SIP-AC). Hear Res 190:109–114
Longenecker RJ, Chonko KT, Maricich SM, Galazyuk AV (2014) Age effects on tinnitus and hearing loss in CBA/CaJ mice following sound exposure. Springerplus 3:542
Luo H, Zhang X, Nation J, Pace E, Lepczyk L, Zhang J (2012) Tinnitus suppression by electrical stimulation of the rat dorsal cochlear nucleus. Neurosci Lett 522:16–20
May B, Moody DB, Stebbins WC (1988) Significant features of Japanese macaque coo sounds: a psychophysical study. Anim Behav 36:1432–1444
May B, Moody DB, Stebbins WC (1989) Categorical perception of conspecific communication sounds by Japanese macaques, Macaca fuscata. J Acoust Soc Am 85:837–847
May BJ, Lauer AM, Roos MJ (2011) Impairments of the medial olivocochlear system increase the risk of noise-induced auditory neuropathy in laboratory mice. Otol Neurotol 32:1568–1578
Moller AR (2016) Sensorineural tinnitus: its pathology and probable therapies. Int J Otolaryngol 2016:2830157
Moody DB (1995) Classification and categorization procedures. In: Klump GM, Dooling RJ, Fay RR, Stebbins WC (eds) Methods in comparative psychoacoustics. Birkhauser Verlag, Basel, pp. 293–306
Ngan EM, May BJ (2001) Relationship between the auditory brainstem response and auditory nerve thresholds in cats with hearing loss. Hear Res 156:44–52
Norman M, Tomscha K, Wehr M (2012) Isoflurane blocks temporary tinnitus. Hear Res 290:64–71
Pace E, Zhang J (2013) Noise-induced tinnitus using individualized gap detection analysis and its relationship with hyperacusis, anxiety, and spatial cognition. PLoS One 8:e75011
Park YM, Na WS, Park IY, Suh MW, Rhee CK, Chung PS, Jung JY (2013) Trans-canal laser irradiation reduces tinnitus perception of salicylate treated rat. Neurosci Lett 544:131–135
Puel JL, Guitton MJ (2007) Salicylate-induced tinnitus: molecular mechanisms and modulation by anxiety. Prog Brain Res 166:141–146
Radziwon KE, Stolzberg DJ, Urban ME, Bowler RA, Salvi RJ (2015) Salicylate-induced hearing loss and gap detection deficits in rats. Front Neurol 6:31
Rüttiger L, Ciuffani J, Zenner H-P, Knipper M (2003) A behavioral paradigm to judge acute sodium salicylate-induced sound experience in rats: a new approach for an animal model on tinnitus. Hear Res 180:39–50
Stolzberg D, Salvi RJ, Allman BL (2012) Salicylate toxicity model of tinnitus. Front Syst Neurosci 6:28
Turner JG, Brozoski TJ, Bauer CA, Parrish JL, Myers K, Hughes LF, Caspary DM (2006) Gap detection deficits in rats with tinnitus: a potential novel screening tool. Behav Neurosci 120:188–195
Wilson PN, Pearce JM (1989) A role for stimulus generalization in conditional discrimination learning. Q J Exp Psychol B 41:243–273
Yang G, Lobarinas E, Zhang L, Turner J, Stolzberg D, Salvi R, Sun W (2007) Salicylate induced tinnitus: behavioral measures and neural activity in auditory cortex of awake rats. Hear Res 226:244–253
Zhang J, Luo H, Pace E, Li L, Liu B (2016) Psychophysical and neural correlates of noised-induced tinnitus in animals: intra- and inter-auditory and non-auditory brain structure studies. Hear Res 334:7–19
Zou D, Huang J, Wu X, Li L (2007) Metabotropic glutamate subtype 5 receptors modulate fear-conditioning induced enhancement of prepulse inhibition in rats. Neuropharmacology 52:476–486
Acknowledgments
This project was initiated in response to the ARO symposium on Assessing Tinnitus in Animals: Progress and Pitfalls (36th Midwinter Meeting, MC Liberman, Chair). The authors thank BL Allman, JI Berger, TJ Brozoski, A Galazyuk, MC Liberman, DB Moody, AR Palmer, MN Wallace, and ED Young for their intellectual contributions during manuscript preparation. Support for this research was provided by the Tinnitus Research Consortium, Action on Hearing Loss, and NIDCD grant P30 DC005211.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Jones, A., May, B.J. Improving the Reliability of Tinnitus Screening in Laboratory Animals. JARO 18, 183–195 (2017). https://doi.org/10.1007/s10162-016-0597-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10162-016-0597-1