Altered intensity coding in the salicylate-overdose animal model of tinnitus
Introduction
Tinnitus is one of the leading disorders of hearing with a high prevalent rate (review see Roberts et al., 2010). In extreme cases, it can be disabling to normal life. Symptoms of this disorder, besides some degree of hearing loss, include: (a) the perception of phantom sound (i.e., in clinical terms, tinnitus); and/or (b) the overly-loud perception of sounds at moderate levels (i.e., in clinical terms, hyperacusis) (Baguley, 2003, Wang et al., 2008). May or may not be related to hyperacusis, a number of electrophysiological recordings from auditory cortex in awake rats showed enhanced responses during experimental tinnitus (e.g., with salicylate overdose or acoustic trauma) (Eggermont, 2013, Lu et al., 2011, Sun et al., 2009, Stolzberg et al., 2012a, Stolzberg et al., 2012b). No effective cure, but only behavioral management is available to treat tinnitus as the underlying pathophysiology still remains unclear (Cazals, 2000, Jastreboff, 2007, Møller, 2007). Research on experimental tinnitus in animals has led to theories of its pathogenesis. The prevailing one is that an initial hearing loss leads to the activation of a central gain control system in order to compensate for the impaired sensory input (Qiu et al., 1999, Norena, 2011). The key issue is therefore the compensation for an altered intensity coding.
One fundamental question in tinnitus regarding the phenomenon of intensity compensation is how the efficiency or precision of intensity coding is altered (i.e., better, no change, or worse). To address this issue, we studied a reversible model of tinnitus that involves salicylate-overdose in rats (Jastreboff et al., 1988, Bauer et al., 1999). Specifically we measured, in their awake state, single-trial auditory evoked responses from the cortex before and after tinnitus-induction. Based on single-trial response strength and its variance, we computed the lower bound of Fisher information at different stimulus levels for an estimation of the coding efficiency of sound intensity (Bethge et al., 2002, Kostal et al., 2013, Roy, 2004).
Below is a brief account of Fisher information with relevance to this study. Fisher information is a measure of the amount of information that an observable random variable (in our case, the strength of evoked potential integral, EPI) carries about an unknown parameter (in our case, the stimulus sound pressure level, or SPL). The probability function for EPI, which is also the likelihood function for SPL, is a function f(EPI; SPL), which describes the probability that we would observe a sample of EPI given a known value of SPL. If f(EPI; SPL) is sharply peaked (or large in size) with respect to SPL, that means it contains a lot of information about SPL, since it is easy to predict the correct value of SPL given the EPI data. Otherwise, if the function is flat (or small in size), it would need more samples of EPI to estimate the correct SPL, and hence the EPI data has less information about SPL (please see Supplementary Text 1 for details).
Section snippets
Animals
Ten adult Sprague Dawley rats (∼6 weeks old, ∼250 g b.w.) were obtained from the Animal Center of National Cheng Kung University (NCKU). Experimental procedures have been approved by the Animal Ethics Committee, NCKU.
Recording electrodes
Bipolar recording electrodes custom-made of Teflon-coated silver wires (125 μm ID, 175 μm OD; A-M Systems, USA) were soldered at one end to miniature strip male-sockets (model 520200; A-M Systems, USA). The recording electrodes contain an active lead and two reference leads which were
Results
Depending on animals, the auditory evoked responses could be of very good signal to noise ratio as shown in Fig. 1. Here the average EP showed clear incremental changes from the control (pre-drug) to the salicylate-treated (post-drug) conditions, with minimal changes in the shape of the response waveform.
From the total of 10 rats studied, 3 of them reached the criterion of good signal-to-noise ratio, and showed significant correspondence with the four-parameter logistic regression function (see
Conclusions and discussion
The principal finding of this study is that during the experimental tinnitus, there is an increase in the efficiency or precision of intensity coding. Furthermore, the increase in J2 is not the same for different sounds (apart from daily variations with identical stimuli, as expected from such behavioral paradigms of passive listening).
First, for tones of different frequencies, high frequency tones (16 kHz in particular) showed significant changes of the response-level function (including an
Acknowledgements
Supported by grants from NCKU, Ministry of Science and Technology, Taiwan, grants 99-2320-B-006-020,100-2923-006-001, 101-2911-I-006-511; as well as by grants from Czech Science Foundation, P303/11/J005, P304/12/1342, 15-08066S.
References (36)
- et al.
Effects of noise and salicylate on auditory evoked-response thresholds in the chinchilla
Hear Res.
(1991) - et al.
Behavioral model of chronic tinnitus in rats
Otolaryngol. Head Neck Surg.
(1999) - et al.
Effects of sodium salicylate on evoked-response measures of hearing
Hear Res.
(1989) Auditory sensori-neural alterations induced by salicylate
Prog. Neurobiol.
(2000)- et al.
hyperacusis, or tinnitus: what is modeled in animal research?
Hear Res.
(2013) - et al.
Auditory evoked responses in control subjects and in patients with problem tinnitus
Hear Res.
(2001) Tinnitus retraining therapy
Prog. Brain Res.
(2007)- et al.
GABAergic neural activity involved in salicylate-induced auditory cortex gain enhancement
Neurosci.
(2011) Tinnitus presence and future
Prog. Brain Res.
(2007)An integrative model of tinnitus based on a central gain controlling neural sensitivity
Neurosci. Biobehav. Rev.
(2011)
Postnatal exposure to tones alters the tuning characteristics of inferior collicular neurons in the rat
Brain Res.
Salicylate-induced tinnitus: molecular mechanisms and modulation by anxiety
Prog. Brain Res.
Contrast gain control in auditory cortex
Neuron
The temporal relationship between the brainstem and primary cortical auditory evoked potentials
Prog. Neurobiol.
Salicylate increases the gain of central auditory system
Neuroscience
Sodium salicylate suppresses serotonin-induced enhancement of GABAergic spontaneous inhibitory postsynaptic currents in rat inferior colliculus in vitro
Hear Res.
Differential changes in Fos-immunoreactivity at the auditory brainstem after chronic injections of salicylate in rats
Hear Res.
Salicylate induced tinnitus: behavioral measures and neural activity in auditory cortex of awake rats
Hear Res.
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