Spontaneous Behavior in Noise and Silence: A Possible New Measure to Assess Tinnitus in Guinea Pigs

Abstract

This study describes two experiments that were conducted in search for a behavioral paradigm to test for tinnitus in guinea pigs. Conditioning paradigms are available to determine the presence of tinnitus in animals and are based on the assumption that tinnitus impairs their ability to detect silent intervals in continuous noise. Guinea pigs have not been subjected to these paradigms yet; therefore, we investigated whether guinea pigs could be conditioned in the two-way shuttle-box paradigm to respond to silent intervals in noise. Even though guinea pigs could be trained relatively easy to respond to the presence of a noise interval, training guinea pigs to silent intervals in noise was unsuccessful. Instead, it appeared that they became immobile when the continuous stimulus was suddenly stopped. This was confirmed by the next experiment, in which we subjected guinea pigs to alternating intervals of noise and silence with a random duration between 30 and 120 s. Indeed, guinea pigs were significantly longer immobile during silence compared to during noise. By interpreting immobility as a signature of perceiving silence, we hypothesized that the presence of tinnitus would reduce immobility in silence. Therefore, we unilaterally exposed one group of guinea pigs to an 11-kHz tone of 124 dB sound pressure level for 1 h. A subset of the exposed animals was significantly more active in silence, but also more active in noise, as compared to the control group. The increased mobility during silent intervals might represent tinnitus. However, the increased mobility in noise of this group implies that the observed behavior could have derived from, e.g., an overall increase in activity. Therefore, conducting validation experiments is very important before implementing this method as a new screening tool for tinnitus. Follow-up experiments are discussed to further elucidate the origin of the increased mobility in both silence and noise.

Recognition of Modified Conditioning Sounds by Competitively Trained Guinea Pigs

“…The GP is a more preferable animal model than rats and mice for research of the cochlear functions and implant, since its cochlea is of an easily accessible size (Pfingst et al, 2011 ; Agterberg and Versnel, 2014 ) and the frequency rage of its audiogram overlaps, especially for the lower part, with that of the human extensively (Heffner et al, 2001 ). Traditionally, hearing capabilities of GPs with cochleae manipulated pharmacologically or mechanically have been evaluated on the basis of discrimination of the tonal quality or sound level (Prosen et al, 1981 ; Nicol et al, 1992 ; Kang et al, 2010 ; Pfingst et al, 2011 ; Dehmel et al, 2012 ; Agterberg and Versnel, 2014 ; Heeringa et al, 2014 ). The present findings showing that the GP has abilities to discriminate sounds differing in spectral and fine temporal structures may facilitate the availability of this animal species for the evaluation of how well the perception of sounds recovered after experimental manipulations.…”

“…More basic functions, such as spatio-temporal representation of acoustic parameters (Taniguchi et al, 1992 ; Bakin et al, 1996 ; Horikawa et al, 1996 ) as well as neural coding of natural sounds, including communication and environment sounds (Suta et al, 2003 ; Syka et al, 2005 ; Wallace et al, 2005 ; Ojima et al, 2010 ; Grimsley et al, 2011a , b ; Gaucher et al, 2013 ), have also been studied with this animal species. Recently, GPs have been used as potential behavioral models for objective demonstration of a subjective phantom sensation, tinnitus (Dehmel et al, 2012 ; Berger et al, 2013 ; Heeringa et al, 2014 ) and to study behavioral responses to intracochlear electrical stimulation (Chikar et al, 2008 ; Kang et al, 2010 ; Agterberg and Versnel, 2014 ). However, it is traditionally known that training GPs is more difficult than training other rodents (Petersen et al, 1977 ; Philippens et al, 1992 ; Agterberg et al, 2010 ), because GPs tend to freeze to novel stimuli especially when stimuli are aversive.…”

The Gap Detection Test

“…However, conductive hearing loss may also cause tinnitus ( Mills & Cherry 1984 ). Consequently, using conductive hearing loss as a control for no-tinnitus cases may not be adequate ( Heeringa et al 2014 ). Thus, although these experiments (Hickox & Liberman 2014; Lobarinas et al 2013 ) cast doubt on the applicability of the gap detection startle paradigm, the validation of behavioral paradigms in animals depends on assumptions the experimenter makes on the presence of tinnitus.…”

Changes in spontaneous movement in response to silent gaps are not robust enough to indicate the perception of tinnitus in mice

“…100% of the 150 SNP markers evenly spaced over the 19 autosomes and the X chromosome were identical in the C57BL/6J colony maintained at the UMCG Central Animal Facility compared to the substrain maintained by Jackson Laboratories (data not shown). The minimum number of experimental animals needed in these experiments (n = 3 mice per experimental group) was statistically calculated using the effect size measured in previous experiments with guinea pig [ 13 ]. In these experiments, repeated measures ANOVA with noised guinea pigs (n = 10) and sham noised guinea pigs (n = 5) yielded an F-statistic of 164.7.…”

“…A recent study identified a novel spontaneous behavior (unconditioned response), changes in movement during silent gaps, that appears to indicate the perception of tinnitus in guinea pigs [ 13 ]. Specifically, guinea pigs identified as perceiving tinnitus after unilateral noise exposure failed to “freeze” in response to silent gaps.…”