Auditory hypersensitivity and processing deficits in a rat model of fragile X syndrome.

Fragile X (FX) syndrome is one of the leading inherited causes of autism spectrum disorder (ASD). A majority of FX and ASD patients exhibit sensory hypersensitivity, including auditory hypersensitivity or hyperacusis, a condition in which everyday sounds are perceived as much louder than normal. Auditory processing deficits in FX and ASD also afford the opportunity to develop objective and quantifiable outcome measures that are likely to translate between humans and animal models due to the well-conserved nature of the auditory system and well-developed behavioral read-outs of sound perception.

Review: Neural Mechanisms of Tinnitus and Hyperacusis in Acute Drug-Induced Ototoxicity.

Purpose Tinnitus and hyperacusis are debilitating conditions often associated with age-, noise-, and drug-induced hearing loss. Because of their subjective nature, the neural mechanisms that give rise to tinnitus and hyperacusis are poorly understood. Over the past few decades, considerable progress has been made in deciphering the biological bases for these disorders using animal models.

Using auditory reaction time to measure loudness growth in rats.

Previous studies have demonstrated that auditory reaction time (RT) is a reliable surrogate of loudness perception in humans. Reaction time-intensity (RT-I) functions faithfully recapitulate equal loudness contours in humans while being easier to obtain than equal loudness judgments, especially in animals. In humans, loudness estimation not only depends on sound intensity, but on a variety of other acoustic factors.

Interaction of auditory and pain pathways: Effects of stimulus intensity, hearing loss and opioid signaling.

Moderate intensity sounds can reduce pain sensitivity (i.e., audio-analgesia) whereas intense sounds can induce aural pain, evidence of multisensory interaction between auditory and pain pathways.

Functional magnetic resonance imaging of enhanced central auditory gain and electrophysiological correlates in a behavioral model of hyperacusis.

Hyperacusis is a debilitating hearing condition in which normal everyday sounds are perceived as exceedingly loud, annoying, aversive or even painful. The prevalence of hyperacusis approaches 10%, making it an important, but understudied medical condition. To noninvasively identify the neural correlates of hyperacusis in an animal model, we used sound-evoked functional magnetic resonance imaging (fMRI) to locate regions of abnormal activity in the central nervous system of rats with behavioral evidence of hyperacusis induced with an ototoxic drug (sodium salicylate, 250 mg/kg, i.

Psychophysical changes in temporal processing in chinchillas with noise-induced hearing loss: A literature review.

It is well-established that excessive noise exposure can systematically shift audiometric thresholds (i.e., noise-induced hearing loss, NIHL) making sounds at the lower end of the dynamic range difficult to detect.

Noise-Induced loudness recruitment and hyperacusis: Insufficient central gain in auditory cortex and amygdala.

Noise-induced hearing loss generally induces loudness recruitment, but sometimes gives rise to hyperacusis, a debilitating condition in which moderate intensity sounds are perceived abnormally loud. In an attempt to develop an animal model of loudness hyperacusis, we exposed rats to a 16-20 kHz noise at 104 dB SPL for 12 weeks. Behavioral reaction time-intensity functions were used to assess loudness growth functions before, during and 2-months post-exposure.

Testing the Central Gain Model: Loudness Growth Correlates with Central Auditory Gain Enhancement in a Rodent Model of Hyperacusis.

The central gain model of hyperacusis proposes that loss of auditory input can result in maladaptive neuronal gain increases in the central auditory system, leading to the over-amplification of sound-evoked activity and excessive loudness perception. Despite the attractiveness of this model, and supporting evidence for it, a critical test of the central gain theory requires that changes in sound-evoked activity be explicitly linked to perceptual alterations of loudness. Here we combined an operant conditioning task that uses a subject's reaction time to auditory stimuli to produce reliable measures of loudness growth with chronic electrophysiological recordings from the auditory cortex and inferior colliculus of awake, behaviorally-phenotyped animals.

Noise-induced hearing loss induces loudness intolerance in a rat Active Sound Avoidance Paradigm (ASAP).

Hyperacusis is a loudness hypersensitivity disorder in which moderate-intensity sounds are perceived as extremely loud, aversive and/or painful. To assess the aversive nature of sounds, we developed an Active Sound Avoidance Paradigm (ASAP) in which rats altered their place preference in a Light/Dark shuttle box in response to sound. When no sound (NS) was present, rats spent more than 95% of the time in the Dark Box versus the transparent Light Box.

Salicylate-induced hyperacusis in rats: Dose- and frequency-dependent effects.

The use of auditory reaction time is a reliable measure of loudness perception in both animals and humans with reaction times (RT) decreasing with increasing stimulus intensity. Since abnormal loudness perception is a common feature of hyperacusis, a potentially debilitating auditory disorder in which moderate-intensity sounds are perceived as uncomfortable or painfully loud, we used RT measures to assess rats for salicylate-induced hyperacusis. A previous study using an operant conditioning RT procedure found that high-dose sodium salicylate (SS) induced hyperacusis-like behavior, i.

Tinnitus and hyperacusis: Contributions of paraflocculus, reticular formation and stress.

Tinnitus and hyperacusis are common and potentially serious hearing disorders associated with noise-, age- or drug-induced hearing loss. Accumulating evidence suggests that tinnitus and hyperacusis are linked to excessive neural activity in a distributed brain network that not only includes the central auditory pathway, but also brain regions involved in arousal, emotion, stress and motor control. Here we examine electrophysiological changes in two novel non-auditory areas implicated in tinnitus and hyperacusis: the caudal pontine reticular nucleus (PnC), involved in arousal, and the paraflocculus lobe of the cerebellum (PFL), implicated in head-eye coordination and gating tinnitus and we measure the changes in corticosterone stress hormone levels.

Inner Hair Cell Loss Disrupts Hearing and Cochlear Function Leading to Sensory Deprivation and Enhanced Central Auditory Gain.

There are three times as many outer hair cells (OHC) as inner hair cells (IHC), yet IHC transmit virtually all acoustic information to the brain as they synapse with 90-95% of type I auditory nerve fibers. Here we review a comprehensive series of experiments aimed at determining how loss of the IHC/type I system affects hearing by selectively destroying these cells in chinchillas using the ototoxic anti-cancer agent carboplatin. Eliminating IHC/type I neurons has no effect on distortion product otoacoustic emission or the cochlear microphonic potential generated by OHC; however, it greatly reduces the summating potential produced by IHC and the compound action potential (CAP) generated by type I neurons.

Audiograms, gap detection thresholds, and frequency difference limens in cannabinoid receptor 1 knockout mice.

The cannabinoid receptor 1 (CB1R) is found at several stages in the auditory pathway, but its role in hearing is unknown. Hearing abilities were measured in CB1R knockout mice and compared to those of wild-type mice. Operant conditioning and the psychophysical Method of Constant Stimuli were used to measure audiograms, gap detection thresholds, and frequency difference limens in trained mice using the same methods and stimuli as in previous experiments.

Tinnitus and hyperacusis involve hyperactivity and enhanced connectivity in auditory-limbic-arousal-cerebellar network.

Hearing loss often triggers an inescapable buzz (tinnitus) and causes everyday sounds to become intolerably loud (hyperacusis), but exactly where and how this occurs in the brain is unknown. To identify the neural substrate for these debilitating disorders, we induced both tinnitus and hyperacusis with an ototoxic drug (salicylate) and used behavioral, electrophysiological, and functional magnetic resonance imaging (fMRI) techniques to identify the tinnitus-hyperacusis network. Salicylate depressed the neural output of the cochlea, but vigorously amplified sound-evoked neural responses in the amygdala, medial geniculate, and auditory cortex.

Salicylate-induced hearing loss and gap detection deficits in rats.

To test the "tinnitus gap-filling" hypothesis in an animal psychoacoustic paradigm, rats were tested using a go/no-go operant gap detection task in which silent intervals of various durations were embedded within a continuous noise. Gap detection thresholds were measured before and after treatment with a dose of sodium salicylate (200 mg/kg) that reliably induces tinnitus in rats. Noise-burst detection thresholds were also measured to document the amount of hearing loss and aid in interpreting the gap detection results.

Behavioral models of tinnitus and hyperacusis in animals.

The phantom perception of tinnitus and reduced sound-level tolerance associated with hyperacusis have a high comorbidity and can be debilitating conditions for which there are no widely accepted treatments. One factor limiting the development of treatments for tinnitus and hyperacusis is the lack of reliable animal behavioral models of these disorders. Therefore, the purpose of this review is to highlight the current animal models of tinnitus and hyperacusis, and to detail the advantages and disadvantages of each paradigm.

Salicylate-induced auditory perceptual disorders and plastic changes in nonclassical auditory centers in rats.

Previous studies have shown that sodium salicylate (SS) activates not only central auditory structures, but also nonauditory regions associated with emotion and memory. To identify electrophysiological changes in the nonauditory regions, we recorded sound-evoked local field potentials and multiunit discharges from the striatum, amygdala, hippocampus, and cingulate cortex after SS-treatment. The SS-treatment produced behavioral evidence of tinnitus and hyperacusis.

Frequency difference limens and auditory cue trading in CBA/CaJ mice (Mus musculus).

Mice are emerging as an important behavioral model for studies of auditory perception and acoustic communication. These mammals frequently produce ultrasonic vocalizations, although the details of how these vocalizations are used for communication are not entirely understood. An important step in determining how they might be differentiating their calls is to measure discrimination and identification of the dimensions of various acoustic stimuli.

Discrimination of ultrasonic vocalizations by CBA/CaJ mice (Mus musculus) is related to spectrotemporal dissimilarity of vocalizations.

The function of ultrasonic vocalizations (USVs) produced by mice (Mus musculus) is a topic of broad interest to many researchers. These USVs differ widely in spectrotemporal characteristics, suggesting different categories of vocalizations, although this has never been behaviorally demonstrated. Although electrophysiological studies indicate that neurons can discriminate among vocalizations at the level of the auditory midbrain, perceptual acuity for vocalizations has yet to be determined.

A novel behavioral assay for the assessment of acute tinnitus in rats optimized for simultaneous recording of oscillatory neural activity.

Background: Human magneto/electrophysiology studies suggest that the phantom sound of tinnitus arises from spontaneous oscillatory neural activity in auditory cortex; however, in animal models, behavioral techniques suitable for testing this hypothesis in combination with electrophysiology recordings have yet to be evaluated. While electrophysiological studies of tinnitus have been reported in passive, awake animals, these studies fail to control for attentional mechanisms likely to play a role in the perception of tinnitus.

New Method: A novel appetitive operant conditioning, two-alternative identification task was developed for detecting acute tinnitus in rats.

Identification of auditory distance cues by zebra finches (Taeniopygia guttata) and budgerigars (Melopsittacus undulatus).

The present study examined auditory distance perception cues in a non-territorial songbird, the zebra finch (Taeniopygia guttata), and in a non-songbird, the budgerigar (Melopsittacus undulatus). Using operant conditioning procedures, three zebra finches and three budgerigars were trained to identify 1- (Near) and 75-m (Far) recordings of three budgerigar contact calls, one male zebra finch song, and one female zebra finch call. Once the birds were trained on these endpoint stimuli, other stimuli were introduced into the operant task.

Behaviorally measured audiograms and gap detection thresholds in CBA/CaJ mice.

Tone detection and temporal gap detection thresholds were determined in CBA/CaJ mice using a Go/No-go procedure and the psychophysical method of constant stimuli. In the first experiment, audiograms were constructed for five CBA/CaJ mice. Thresholds were obtained for eight pure tones ranging in frequency from 1 to 42 kHz.