Publications using the System 3

This study was designed to address individual differences in aided speech understanding among a relatively large group of older adults. The group of older adults consisted of 98 adults (50 female and 48 male) ranging in age from 60 to 86 (mean = 69.2). Hearing loss was typical for this age group and about 90% had not worn hearing aids. All subjects completed a battery of tests, including cognitive (6 measures), psychophysical (17 measures), and speech-understanding (9 measures), as well as the Speech, Spatial, and Qualities of Hearing (SSQ) self-report scale. Most of the speech-understanding measures made use of competing speech and the non-speech psychophysical measures were designed to tap phenomena thought to be relevant for the perception of speech in competing speech (e.g., stream segregation, modulation-detection interference). All measures of speech understanding were administered with spectral shaping applied to the speech stimuli to fully restore audibility through at least 4000 Hz. The measures used were demonstrated to be reliable in older adults and, when compared to a reference group of 28 young normal-hearing adults, age-group differences were observed on many of the measures. Principal-components factor analysis was applied successfully to reduce the number of independent and dependent (speech understanding) measures for a multiple-regression analysis. Doing so yielded one global cognitive-processing factor and five non-speech psychoacoustic factors (hearing loss, dichotic signal detection, multi-burst masking, stream segregation, and modulation detection) as potential predictors. To this set of six potential predictor variables were added subject age, Environmental Sound Identification (ESI), and performance on the text-recognition-threshold (TRT) task (a visual analog of interrupted speech recognition). These variables were used to successfully predict one global aided speech-understanding factor, accounting for about 60% of the variance.

Age-related impairments in the primary auditory cortex (A1) include poor tuning selectivity, neural desynchronization, and degraded responses to low-probability sounds. These changes have been largely attributed to reduced inhibition in the aged brain, and are thought to contribute to substantial hearing impairment in both humans and animals. Since many of these changes can be partially reversed with auditory training, it has been speculated that they might not be purely degenerative, but might rather represent negative plastic adjustments to noisy or distorted auditory signals reaching the brain. To test this hypothesis, we examined the impact of exposing young adult rats to 8 weeks of low-grade broadband noise on several aspects of A1 function and structure. We then characterized the same A1 elements in aging rats for comparison. We found that the impact of noise exposure on A1 tuning selectivity, temporal processing of auditory signal and responses to oddball tones was almost indistinguishable from the effect of natural aging. Moreover, noise exposure resulted in a reduction in the population of parvalbumin inhibitory interneurons and cortical myelin as previously documented in the aged group. Most of these changes reversed after returning the rats to a quiet environment. These results support the hypothesis that age-related changes in A1 have a strong activity-dependent component and indicate that the presence or absence of clear auditory input patterns might be a key factor in sustaining adult A1 function.

Numerous recent reports have suggested that individuals deprived of vision are able to develop heightened auditory spatial abilities. However, most such studies have compared the blind to blindfolded sighted individuals, a procedure that might introduce a strong performance bias. Indeed, while blind individuals have had their whole lives to adapt to this condition, sighted individuals might be put at a severe disadvantage when having to localize sounds without visual input. To address this unknown, we compared the sound localization ability of eight sighted individuals with and without a blindfold in a hemi-anechoic chamber. Sound stimuli were broadband noise delivered via two speaker arrays: a horizontal array with 25 loudspeakers (ranging from -90° to +90°; 7.5°) and a vertical array with 16 loudspeakers (ranging from -45° to +67.5°). A factorial design was used, where we compared two vision conditions (blindfold vs. non-blindfold), two sound planes (horizontal vs. vertical) and two pointing methods (hand vs. head). Results show that all three factors significantly interact with one another with regards to the average absolute deviation error. Although blindfolding significantly affected all conditions, it did more so for head-pointing in the horizontal plane. Moreover, blindfolding was found to increase the tendency to undershoot more eccentric spatial positions for head-pointing, but not hand-pointing. Overall, these findings suggest that while proprioceptive cues appear to be sufficient for accurate hand pointing in the absence of visual feedback, head pointing relies more heavily on visual cues in order to provide a precise response. It also strongly argues against the use of head pointing methodologies with blindfolded sighted individuals, particularly in the horizontal plane, as it likely introduces a bias when comparing them to blind individuals.

Daily our central nervous system receives inputs via several sensory modalities, processes them and integrates information in order to produce a suitable behavior. The amazing part is that such a multisensory integration brings all information into a unified percept. An approach to start investigating this property is to show that perception is better and faster when multimodal stimuli are used as compared to unimodal stimuli. This forms the first part of the present study conducted in a non-human primate's model (n = 2) engaged in a detection sensory-motor task where visual and auditory stimuli were displayed individually or simultaneously. The measured parameters were the reaction time (RT) between stimulus and onset of arm movement, successes and errors percentages, as well as the evolution as a function of time of these parameters with training. As expected, RTs were shorter when the subjects were exposed to combined stimuli. The gains for both subjects were around 20 and 40 ms, as compared with the auditory and visual stimulus alone, respectively. Moreover the number of correct responses increased in response to bimodal stimuli. We interpreted such multisensory advantage through redundant signal effect which decreases perceptual ambiguity, increases speed of stimulus detection, and improves performance accuracy. The second part of the study presents single-unit recordings derived from the premotor cortex (PM) of the same subjects during the sensory-motor task. Response patterns to sensory/multisensory stimulation are documented and specific type proportions are reported. Characterization of bimodal neurons indicates a mechanism of audio-visual integration possibly through a decrease of inhibition. Nevertheless the neural processing leading to faster motor response from PM as a polysensory association cortical area remains still unclear.

Cyclodextrins are sugar compounds that are increasingly finding medicinal uses due to their ability to complex with hydrophobic molecules. One cyclodextrin in particular, 2-hydroxypropyl-β-cyclodextrin (HPβCD), is used as a carrier to solubilize lipophilic drugs and is itself being considered as a therapeutic agent for treatment of Niemann-Pick Type C disease, due to its ability to mobilize cholesterol. Results from toxicological studies suggest that HPβCD is generally safe, but a recent study has found that it causes hearing loss in cats. Whether the hearing loss occurred via death of cochlear hair cells, rendering it permanent, was unexplored. In the present study, we examined peripheral auditory function and cochlear histology in mice after subcutaneous injection of HPβCD to test for hearing loss and correlate any observed auditory deficits with histological findings. On average, auditory brainstem response thresholds were elevated at 4, 16, and 32 kHz in mice one week after treatment with 8,000 mg/kg. In severely affected mice all outer hair cells were missing in the basal half of the cochlea. In many cases, surviving hair cells in the cochlear apex exhibited abnormal punctate distribution of the motor protein prestin, suggesting long term changes to membrane composition and integrity. Mice given a lower dose of 4,000 mg/kg exhibited hearing loss only after repeated doses, but these threshold shifts were temporary. Therefore, cyclodextrin-induced hearing loss was complex, involving cell death and other more subtle influences on cochlear physiology.

Noise-exposure at levels low enough to avoid a permanent threshold shift has been found to cause a massive, delayed degeneration of spiral ganglion neurons (SGNs) in mouse cochleae. Damage to the afferent innervation was initiated by a loss of synaptic ribbons, which is largely irreversible in mice. A similar delayed loss of SGNs has been found in guinea pig cochleae, but at a reduced level, suggesting a cross-species difference in SGN sensitivity to noise. Ribbon synapse damage occurs "silently" in that it does not affect hearing thresholds as conventionally measured, and the functional consequence of this damage is not clear. In the present study, we further explored the effect of noise on cochlear afferent innervation in guinea pigs by focusing on the dynamic changes in ribbon counts over time, and resultant changes in temporal processing. It was found that (1) contrary to reports in mice, the initial loss of ribbons largely recovered within a month after the noise exposure, although a significant amount of residual damage existed; (2) while the response threshold fully recovered in a month, the temporal processing continued to be deteriorated during this period.

How the brain maintains an accurate and stable representation of visual target locations despite the occurrence of saccadic gaze shifts is a classical problem in oculomotor research. Here we test and dissociate the predictions of different conceptual models for head-unrestrained gaze-localization behavior of macaque monkeys. We adopted the double-step paradigm with rapid eye-head gaze shifts to measure localization accuracy in response to flashed visual stimuli in darkness. We presented the second target flash either before (static), or during (dynamic) the first gaze displacement. In the dynamic case the brief visual flash induced a small retinal streak of up to about 20 deg at an unpredictable moment and retinal location during the eye-head gaze shift, which provides serious challenges for the gaze-control system. However, for both stimulus conditions, monkeys localized the flashed targets with accurate gaze shifts, which rules out several models of visuomotor control. First, these findings exclude the possibility that gaze-shift programming relies on retinal inputs only. Instead, they support the notion that accurate eye-head motor feedback updates the gaze-saccade coordinates. Second, in dynamic trials the visuomotor system cannot rely on the coordinates of the planned first eye-head saccade either, which rules out remapping on the basis of a predictive corollary gaze-displacement signal. Finally, because gaze-related head movements were also goal-directed, requiring continuous access to eye-in-head position, we propose that our results best support a dynamic feedback scheme for spatial updating in which visuomotor control incorporates accurate signals about instantaneous eye- and head positions rather than relative eye- and head displacements.

There is accumulating evidence that prior knowledge about expectations plays an important role in perception. The Bayesian framework is the standard computational approach to explain how prior knowledge about the distribution of expected stimuli is incorporated with noisy observations in order to improve performance. However, it is unclear what information about the prior distribution is acquired by the perceptual system over short periods of time and how this information is utilized in the process of perceptual decision making. Here we address this question using a simple two-tone discrimination task. We find that the "contraction bias", in which small magnitudes are overestimated and large magnitudes are underestimated, dominates the pattern of responses of human participants. This contraction bias is consistent with the Bayesian hypothesis in which the true prior information is available to the decision-maker. However, a trial-by-trial analysis of the pattern of responses reveals that the contribution of most recent trials to performance is overweighted compared with the predictions of a standard Bayesian model. Moreover, we study participants' performance in a-typical distributions of stimuli and demonstrate substantial deviations from the ideal Bayesian detector, suggesting that the brain utilizes a heuristic approximation of the Bayesian inference. We propose a biologically plausible model, in which decision in the two-tone discrimination task is based on a comparison between the second tone and an exponentially-decaying average of the first tone and past tones. We show that this model accounts for both the contraction bias and the deviations from the ideal Bayesian detector hypothesis. These findings demonstrate the power of Bayesian-like heuristics in the brain, as well as their limitations in their failure to fully adapt to novel environments.

Spatial release from masking refers to a benefit for speech understanding. It occurs when a target talker and a masker talker are spatially separated. In those cases, speech intelligibility for target speech is typically higher than when both talkers are at the same location. In cochlear implant listeners, spatial release from masking is much reduced or absent compared with normal hearing listeners. Perhaps this reduced spatial release occurs because cochlear implant listeners cannot effectively attend to spatial cues. Three experiments examined factors that may interfere with deploying spatial attention to a target talker masked by another talker. To simulate cochlear implant listening, stimuli were vocoded with two unique features. First, we used 50-Hz low-pass filtered speech envelopes and noise carriers, strongly reducing the possibility of temporal pitch cues; second, co-modulation was imposed on target and masker utterances to enhance perceptual fusion between the two sources. Stimuli were presented over headphones. Experiments 1 and 2 presented high-fidelity spatial cues with unprocessed and vocoded speech. Experiment 3 maintained faithful long-term average interaural level differences but presented scrambled interaural time differences with vocoded speech. Results show a robust spatial release from masking in Experiments 1 and 2, and a greatly reduced spatial release in Experiment 3. Faithful long-term average interaural level differences were insufficient for producing spatial release from masking. This suggests that appropriate interaural time differences are necessary for restoring spatial release from masking, at least for a situation where there are few viable alternative segregation cues.

Key points The cerebral cortex plays a critical role in perception and in learning‐induced plasticity. We show that reversibly silencing any of the main regions of auditory cortex impairs the ability of adult ferrets to localize sound, with the largest deficit seen after deactivating the primary fields. Although these animals had no trouble localizing longer sound bursts, their performance dropped considerably when auditory spatial cues were altered by occluding one ear with an earplug. In contrast to control ferrets, which recovered their localization abilities with intensive training, adaptation to an earplug was impaired following cortical inactivation, with the greatest disruption in plasticity observed after silencing higher‐level cortical areas. These findings imply regional differences in the processing of spatial information across the auditory cortex. Abstract The contribution of auditory cortex to spatial information processing was explored behaviourally in adult ferrets by reversibly deactivating different cortical areas by subdural placement of a polymer that released the GABA A agonist muscimol over a period of weeks. The spatial extent and time course of cortical inactivation were determined electrophysiologically. Muscimol‐Elvax was placed bilaterally over the anterior (AEG), middle (MEG) or posterior ectosylvian gyrus (PEG), so that different regions of the auditory cortex could be deactivated in different cases. Sound localization accuracy in the horizontal plane was assessed by measuring both the initial head orienting and approach‐to‐target responses made by the animals. Head orienting behaviour was unaffected by silencing any region of the auditory cortex, whereas the accuracy of approach‐to‐target responses to brief sounds (40 ms noise bursts) was reduced by muscimol‐Elvax but not by drug‐free implants. Modest but significant localization impairments were observed after deactivating the MEG, AEG or PEG, although the largest deficits were produced in animals in which the MEG, where the primary auditory fields are located, was silenced. We also examined experience‐induced spatial plasticity by reversibly plugging one ear. In control animals, localization accuracy for both approach‐to‐target and head orienting responses was initially impaired by monaural occlusion, but recovered with training over the next few days. Deactivating any part of the auditory cortex resulted in less complete recovery than in controls, with the largest deficits observed after silencing the higher‐level cortical areas in the AEG and PEG. Although suggesting that each region of auditory cortex contributes to spatial learning, differences in the localization deficits and degree of adaptation between groups imply a regional specialization in the processing of spatial information across the auditory cortex.

Tinnitus is an auditory phenomenon characterised by the perception of a sound in the absence of an external auditory stimulus. Chronic subjective tinnitus is almost certainly maintained via central mechanisms, and this is consistent with observed measures of altered spontaneous brain activity. A number of putative central auditory mechanisms for tinnitus have been proposed. The influential thalamocortical dysrhythmia model suggests that tinnitus can be attributed to the disruption of coherent oscillatory activity between thalamus and cortex following hearing loss. However, the extent to which this disruption specifically contributes to tinnitus or is simply a consequence of the hearing loss is unclear because the necessary matched controls have not been tested. Here, we rigorously test several predictions made by this model in four groups of participants (tinnitus with hearing loss, tinnitus with clinically normal hearing, no tinnitus with hearing loss and no tinnitus with clinically normal hearing). Magnetoencephalography was used to measure oscillatory brain activity within different frequency bands in a 'resting' state and during presentation of a masking noise. Results revealed that low-frequency activity in the delta band (1-4 Hz) was significantly higher in the 'tinnitus with hearing loss' group compared to the 'no tinnitus with normal hearing' group. A planned comparison indicated that this effect was unlikely to be driven by the hearing loss alone, but could possibly be a consequence of tinnitus and hearing loss. A further interpretative linkage to tinnitus was given by the result that the delta activity tended to reduce when tinnitus was masked. High-frequency activity in the gamma band (25-80 Hz) was not correlated with tinnitus (or hearing loss). The findings partly support the thalamocortical dysrhythmia model and suggest that slow-wave (delta band) activity may be a more reliable correlate of tinnitus than high-frequency activity.

The saliency of visual objects is based on the center to background contrast. Particularly objects differing in one feature from the background may be perceived as more salient. It is not clear to what extent this so called "pop-out" effect observed in humans and primates governs saliency perception in non-primates as well. In this study we searched for neural-correlates of pop-out perception in neurons located in the optic tectum of the barn owl. We measured the responses of tectal neurons to stimuli appearing within the visual receptive field, embedded in a large array of additional stimuli (the background). Responses were compared between contrasting and uniform conditions. In a contrasting condition the center was different from the background while in the uniform condition it was identical to the background. Most tectal neurons responded better to stimuli in the contrsating condition compared to the uniform condition when the contrast between center and background was the direction of motion but not when it was the orientation of a bar. Tectal neurons also preferred contrasting over uniform stimuli when the center was looming and the background receding but not when the center was receding and the background looming. Therefore, our results do not support the hypothesis that tectal neurons are sensitive to pop-out per-se. The specific sensitivity to the motion contrasting stimulus is consistent with the idea that object motion and not large field motion (e.g., self-induced motion) is coded in the neural responses of tectal neurons.

Background In a natural environment, contextual noise frequently occurs with a signal sound for detection or discrimination in a temporal relation. However, the representation of sound frequency by auditory cortical neurons in a noisy environment is not fully understood. Therefore, the purpose of this study was to explore the impact of contextual noise on the cortical tuning to signal sound frequency in order to better understand the mechanism of cortical frequency coding in a complex acoustical environment. Results We compared the excitatory frequency-level receptive fields (FLRFs) of neurons in the rat primary auditory cortex determined under both quiet and preceding noise conditions. Based on the changes of minimum threshold and the extent of FLRF of auditory cortical neurons, we found that the FLRFs of a cortical neuron were modulated dynamically by a varying preceding noise. When the interstimulus interval between noise and the probe tone was constant, the modulation of the FLRF increased as the level of noise was increased. If the preceding noise level was constant, the modulation decreased when the interstimulus interval was increased. Preceding noise sharpened the bandwidth of the FLRFs of 47.6% tested neurons. Moreover, preceding noise shifted the CFs of 47.6% neurons by more than 0.25 octaves, while the CFs of the rest of the neurons remained relatively unchanged. Conclusions The results indicate that the cortical representation of sound frequency is dynamically modulated by contextual acoustical environment, and that there are cortical neurons whose characteristic frequencies were resistant to the interference of contextual noise.

To date, the functional and physiological impact on the mature brain of moderate-level environmental noises that do not cause noticeable peripheral deficits remains largely unstudied. Here we show that exposing adult rats to structured noise at a sound pressure level of 65 dB, which is markedly below the broadly accepted safety level standard, results in behavioural impairments and substantially impairs the function of the auditory cortex. The strong deterioration in cortical processing of acoustic inputs is independent of the modulation rates of structured noises. Almost equally strong effects result from 10-h daily versus 24-h daily exposure regimens. These results indicate that there can be substantial negative consequences for the auditory system documented at the cortical level, attributable to environmental exposure to structured noises delivered under conditions that do not directly impact hearing sensitivity. These noises are deemed to be 'safe' and are often present in modern human environments.

A large proportion of age-related hearing loss is caused by loss or damage to outer hair cells in the organ of Corti. The organ of Corti is the mechanosensory transducing apparatus in the inner ear and is composed of inner hair cells, outer hair cells, and highly specialized supporting cells. The mechanisms that regulate differentiation of inner and outer hair cells are not known. Here we report that fibroblast growth factor 20 (FGF20) is required for differentiation of cells in the lateral cochlear compartment (outer hair and supporting cells) within the organ of Corti during a specific developmental time. In the absence of FGF20, mice are deaf and lateral compartment cells remain undifferentiated, postmitotic, and unresponsive to Notch-dependent lateral inhibition. These studies identify developmentally distinct medial (inner hair and supporting cells) and lateral compartments in the developing organ of Corti. The viability and hearing loss in Fgf20 knockout mice suggest that FGF20 may also be a deafness-associated gene in humans.

Aminoglycosides, such as gentamycin, are well known ototoxic agents. Toxicity occurs via an activation process involving the formation of an iron-gentamycin complex with free radical production. Antioxidants like Q-ter (a soluble formulation of coenzyme Q(10), CoQ(10)), can limit or prevent cellular ototoxic damage. The present study was designed to investigate the possible protective effects of Q-ter on gentamycin ototoxicity in albino guinea pigs (250-300 g). Animals were divided into five experimental groups: I, a sham control group given an intra-peritoneal (I.P.) injection of 0.5 ml saline (SHAM); II, gentamycin group (GM), treated with an injection of gentamycin (100 mg/ kg); III, gentamycin + Q-ter group (GM+Q-ter), treated with gentamycin (same dose as group II) and an I.P. injection of coenzyme Q(10) terclatrate (Q-ter) at 100 mg/kg body weight; IV, injected with gentamycin (100 mg/kg) plus saline; V, treated with Q-ter alone (100 mg/ kg). All animals were treated for 14 consecutive days. Auditory function was evaluated by recording auditory brainstem responses (ABR) at 15 and 30 days from the beginning of treatment. Morphological changes were analyzed by rhodamine-phalloidine staining. Gentamycin-induced progressive high-frequency hearing loss of 45-55 dB SPL. Q-ter therapy slowed and attenuated the progression of hearing loss, yielding a threshold shift of 20 dB. The significant loss of outer hair cells (OHCs) in the cochlear medio-basal turn in gentamycin-treated animals was not observed in the cochleae of animals protected with Q-ter. This study supports the hypothesis that Q-ter interferes with gentamycin-induced free radical formation, and suggests that it may be useful in protecting OHC function from aminoglycoside ototoxicity, thus reducing hearing loss.

Studies on the maturation of auditory motion processing in children have yielded inconsistent reports. The present study combines subjective and objective measurements to investigate how the auditory perceptual abilities of children change during development and whether these changes are paralleled by changes in the event-related brain potential (ERP). We employed the mismatch negativity (MMN) to determine maturational changes in the discrimination of interaural time differences (ITDs) that generate lateralized moving auditory percepts. MMNs were elicited in children, teenagers, and adults, using a small and a large ITD at stimulus offset with respect to each subject's discrimination threshold. In adults and teenagers large deviants elicited prominent MMNs, whereas small deviants at the behavioral threshold elicited only a marginal or no MMN. In contrast, pronounced MMNs for both deviant sizes were found in children. Behaviorally, however, most of the children showed higher discrimination thresholds than teens and adults. Although automatic ITD detection is functional, active discrimination is still limited in children. The lack of MMN deviance dependency in children suggests that unlike in teenagers and adults, neural signatures of automatic auditory motion processing do not mirror discrimination abilities. The study critically accounts for advanced understanding of children's central auditory development.

Damage to the auditory system following high-level sound exposure reduces afferent input. Homeostatic mechanisms appear to compensate for the loss. Overcompensation may produce the sensation of sound without an objective physical correlate, i.e., tinnitus. Several potential compensatory neural processes have been identified, such as increased spontaneous activity. The cellular mechanisms enabling such compensatory processes may involve down-regulation of inhibitory neurotransmission mediated by γ-amino butyric acid (GABA), and/or up-regulation of excitatory neurotransmission, mediated by glutamic acid (Glu). Because central processing systems are integrated and well-regulated, compensatory changes in one system may produce reactive changes in others. Some or all may be relevant to tinnitus. To examine the roles of GABA and Glu in tinnitus, high resolution point-resolved proton magnetic resonance spectroscopy ((1)H-MRS) was used to quantify their levels in the dorsal cochlear nucleus (DCN), inferior colliculus (IC), medial geniculate body (MGB), and primary auditory cortex (A1) of rats. Chronic tinnitus was produced by a single high-level unilateral exposure to noise, and was measured using a psychophysical procedure sensitive to tinnitus. Decreased GABA levels were evident only in the MGB, with the greatest decrease, relative to unexposed controls, obtained in the contralateral MGB. Small GABA increases may have been present bilaterally in A1 and in the contralateral DCN. Although Glu levels showed considerable variation, Glu was moderately and bilaterally elevated both in the DCN and in A1. In the MGB Glu was increased ipsilaterally but decreased contralaterally. These bidirectional and region-specific alterations in GABA and Glu may reflect large-scale changes in inhibitory and excitatory equilibrium accompanying chronic tinnitus. The present results also suggest that targeting both neurotransmitter systems may be optimal in developing more effective therapeutics.

Hypothyroidism is a cause of genetic and environmentally induced deafness. The sensitivity of cochlear development and function to thyroid hormone (TH) mandates understanding TH action in this sensory organ. Prop1(df) and Pou1f1(dw) mutant mice carry mutations in different pituitary transcription factors, each resulting in pituitary thyrotropin deficiency. Despite the same lack of detectable serum TH, these mutants have very different hearing abilities: Prop1(df) mutants are mildly affected, while Pou1f1(dw) mutants are completely deaf. Genetic studies show that this difference is attributable to the genetic backgrounds. Using embryo transfer, we discovered that factors intrinsic to the fetus are the major contributor to this difference, not maternal effects. We analyzed Prop1(df) mutants to identify processes in cochlear development that are disrupted in other hypothyroid animal models but protected in Prop1(df) mutants by the genetic background. The development of outer hair cell (OHC) function is delayed, but Prestin and KCNQ4 immunostaining appear normal in mature Prop1(df) mutants. The endocochlear potential and KCNJ10 immunostaining in the stria vascularis are indistinguishable from wild type, and no differences in neurofilament or synaptophysin staining are evident in Prop1(df) mutants. The synaptic vesicle protein otoferlin normally shifts expression from OHC to IHC as temporary afferent fibers beneath the OHC regress postnatally. Prop1(df) mutants exhibit persistent, abnormal expression of otoferlin in apical OHC, suggesting delayed maturation of synaptic function. Thus, the genetic background of Prop1(df) mutants is remarkably protective for most functions affected in other hypothyroid mice. The Prop1(df) mutant is an attractive model for identifying the genes that protect against deafness.