Auditory Research publications

In vertebrates, any transmission of vocal signals faces the challenge of acoustic interferences such as heavy rain, wind, animal, or urban sounds. Consequently, several mechanisms and strategies have evolved to optimize the signal-to-noise ratio. Examples to increase detectability are the Lombard effect, an involuntary rise in call amplitude in response to masking ambient noise, which is often associated with several other vocal changes such as call frequency and duration, as well as the animals’ capability of limiting calling to periods where noise perturbation is absent. Previous studies revealed rapid vocal flexibility and various audio-vocal integration mechanisms in marmoset monkeys. Using acoustic perturbation triggered by vocal behavior, we investigated whether marmoset monkeys are capable of exhibiting changes in call structure when perturbing noise starts after call onset or whether such effects only occur if noise perturbation starts prior to call onset. We show that marmoset monkeys are capable of rapidly modulating call amplitude and frequency in response to such perturbing noise bursts. Vocalizations swiftly increased call frequency after noise onset indicating a rapid effect of perturbing noise on vocal motor pattern production. Call amplitudes were also affected. Interestingly, however, the marmosets did not exhibit the Lombard effect as previously reported but decreased their call intensity in response to perturbing noise. Our findings indicate that marmosets possess a general avoidance strategy to call in the presences of ambient noise and suggest that these animals are capable of counteracting a previously thought involuntary audio-vocal mechanism, the Lombard effect, presumably via cognitive control processes.

In the rodent auditory system, the primary cortex is subdivided into two regions, both receiving direct inputs from the auditory thalamus: the primary auditory cortex (A1) and the anterior auditory field (AAF). Although neurons in the two regions display different response properties, like response latency, firing threshold or tuning bandwidth, it is still not clear whether they process sound in a distinct way. Using in vivo electrophysiological recordings in the mouse auditory cortex, we found that AAF neurons have significantly stronger responses to tone offset than A1 neurons. AAF neurons also display faster and more transient responses than A1 neurons. Additionally, offset responses in AAF – unlike in A1, increase with sound duration. Local field potential (LFP) and laminar analyses suggest that the differences in sound responses between these two primary cortices are both of subcortical and intracortical origin. These results emphasize the potentially critical role of AAF for temporal processing. Our study reveals a distinct role of two primary auditory cortices in tone processing and highlights the complexity of sound encoding at the cortical level.

Detecting rapid, coincident changes across sensory modalities is essential for recognition of sudden threats or events. Using two-photon calcium imaging in identified cell types in awake, head-fixed mice, we show that, among the basic features of a sound envelope, loud sound onsets are a dominant feature coded by the auditory cortex neurons projecting to primary visual cortex (V1). In V1, a small number of layer 1 interneurons gates this cross-modal information flow in a context-dependent manner. In dark conditions, auditory cortex inputs lead to suppression of the V1 population. However, when sound input coincides with a visual stimulus, visual responses are boosted in V1, most strongly after loud sound onsets. Thus, a dynamic, asymmetric circuit connecting AC and V1 contributes to the encoding of visual events that are coincident with sounds.

Partial hearing loss can cause neurons in the auditory and audiovisual cortices to increase their responsiveness to visual stimuli; however, behavioral studies in hearing-impaired humans and rats have found that the perceptual ability to accurately judge the relative timing of auditory and visual stimuli is largely unaffected. To investigate the neurophysiological basis of how audiovisual temporal acuity may be preserved in the presence of hearing loss-induced crossmodal plasticity, we exposed adult rats to loud noise and two weeks later performed in vivo electrophysiological recordings in two neighboring regions within the lateral extrastriate visual (V2L) cortex—a multisensory zone known to be responsive to audiovisual stimuli (V2L-Mz) and a predominantly auditory zone (V2L-Az). To examine the cortical layer-specific effects at the level of postsynaptic potentials, a current source density (CSD) analysis was applied to the local field potential (LFP) data recorded in response to auditory and visual stimuli presented at various stimulus onset asynchronies (SOAs). As predicted, differential effects were observed in the neighboring cortical regions’ postnoise exposure. Most notably, an analysis of the strength of multisensory response interactions revealed that V2L-Mz lost its sensitivity to the relative timing of the auditory and visual stimuli, due to an increased responsiveness to visual stimulation that produced a prominent audiovisual response irrespective of the SOA. In contrast, not only did the V2L-Az in noise-exposed rats become more responsive to visual stimuli but neurons in this region also inherited the capacity to process audiovisual stimuli with the temporal precision and specificity that was previously restricted to the V2L-Mz. Thus, the present study provides the first demonstration that audiovisual temporal processing can be preserved following moderate hearing loss via compensatory plasticity in the higher-order sensory cortices that is ultimately characterized by a functional transition in the cortical region capable of temporal sensitivity.

In this study, we investigated the role of MAP kinase phosphatase-1 (MKP-1) and rosiglitazone (RSG) in glucocorticoid resistance and glucocorticoid sensitivity, respectively, using a guinea pig model of lipopolysaccharide- (LPS-) induced sudden sensorineural hearing loss (SSHL). The pigs were divided into control, LPS, LPS+dexamethasone (DEX), LPS+RSG, and LPS+DEX+RSG groups. Their hearing was screened by auditory brainstem response measurement. Immunofluorescence staining was used to identify the location of MKP-1 in the inner ear. The expression levels of MKP-1 and the related proteins in the inner ear were detected using western blotting. The morphological changes in the cochlea were observed via hematoxylin-eosin staining. Severe hearing loss was observed in the LPS group, as opposed to the protection from hearing loss observed in the LPS+DEX+RSG group. A positive correlation was observed between MKP-1 expression levels and protection from hearing loss. RSG and DEX synergistically influenced inner ear inflammation. In conclusion, resistance of LPS-induced SSHL guinea pig models to glucocorticoids may result from impaired MKP-1 function in inner ear tissues, induced by glucocorticoids, impairing the inhibition of inflammation. Our findings present novel targets to develop potential therapeutics to treat inflammatory diseases of the inner ear.

Accurate sound localization requires normal binaural input and precise auditory neuronal representation of sound spatial locations. Previous studies showed that unilateral hearing loss profoundly impaired the sound localization abilities. However, the underlying neural mechanism is not fully understood. Here, we investigated how chronic unilateral conductive hearing loss (UCHL) affected the neural tuning to sound source azimuth in the primary auditory cortex (AI). The UCHL was manipulated by the removal of tympanic membrane and malleus in the right ear of young (P14) rats and adult (P57) rats. We recorded the azimuth tuning of neurons in the left AI contralateral to the operated ear in the two groups of rats that experienced 2 months of UCHL, and in the left AI of age-matched control rats. We found that AI neurons in control rats showed predominant preference to sound from contralateral azimuths. However, UCHL weakened the cortical neuronal representation of contralateral azimuths on the operated ear side and strengthened the cortical neuronal representation of ipsilateral azimuths on the intact ear side. This effect was stronger in rats with UCHL at young age than in rats with UCHL in adulthood. Moreover, UCHL degraded the azimuth selectivity and azimuth sensitivity of AI neurons, and this effect was stronger in rats with UCHL in adulthood than in rats with UCHL at young age. These findings highlight a remarkable age-related experience-dependent plasticity of neural tuning to sound source azimuth in AI, and imply a neural mechanism for the impacts of chronic UCHL on sound localization abilities.

Rat auditory cortex was subjected to 0.1 mA anodal direct current in seven 10-min sessions on alternate days. Based on the well-known auditory cortex control of olivocochlear regulation through corticofugal projections, auditory brainstem responses (ABRs) were recorded as an indirect test of the effectiveness and reversibility of the multisession protocol of epidural stimulation. Increases of 20-30 dB ABR auditory thresholds shown after epidural stimulation reverted back to control levels 10 min after a single session. However, increases in thresholds revert 4 days after multisession stimulation. Less changes in wave amplitudes and threshold shifts were shown in ABR recorded contralaterally to the electrically stimulated side of the brain. To assess tissue effects of epidural electric stimulation on the brain cortex, well characterized functional anatomical markers of glial cells (GFAP/astrocytes and Iba1/microglial cells) and neurons (c-Fos) were analyzed in alternate serial sections by quantitative immunocytochemistry. Restricted astroglial and microglial reactivity was observed within the cytoarchitectural limits of the auditory cortex. However, interstitial GFAP overstaining was also observed in the ventricular surface and around blood vessels, thus supporting a potential global electrolytic stimulation of the brain. These results correlate with extensive changes in the distribution of c-Fos immunoreactive neurons among layers along sensory cortices after multisession stimulation. Quantitative immunocytochemical analysis supported this idea by showing a significant increase in the number of positive neurons in supragranular layers and a decrease in layer 6 with no quantitative changes detected in layer 5. Our data indicate that epidural stimulation of the auditory cortex induces a reversible decrease in hearing sensitivity due to local, restricted epidural stimulation. A global plastic response of the sensory cortices, also reported here, may be related to electrolytic effects of electric currents.

Salience is a broad and widely used concept in neuroscience whose neuronal correlates, however, remain elusive. In behavioral conditioning, salience is used to explain various effects, such as stimulus overshadowing, and refers to how fast and strongly a stimulus can be associated with a conditioned event. Here, we identify sounds of equal intensity and perceptual detectability, which due to their spectro-temporal content recruit different levels of population activity in mouse auditory cortex. When using these sounds as cues in a Go/NoGo discrimination task, the degree of cortical recruitment matches the salience parameter of a reinforcement learning model used to analyze learning speed. We test an essential prediction of this model by training mice to discriminate light-sculpted optogenetic activity patterns in auditory cortex, and verify that cortical recruitment causally determines association or overshadowing of the stimulus components. This demonstrates that cortical recruitment underlies major aspects of stimulus salience during reinforcement learning.

Objectives: Voltage-gated Ca2+ channels (VGCCs) are of central relevance in regulating Ca2+ influx into living cells. The low-voltage activated (LVA) Cav3 T-type Ca2+ channels are widely distributed throughout the brain including the peripheral auditory system and ascending auditory tract. Their exact role in auditory information processing is still not fully understood. Within the LVA subgroup, Cav3.2 T-type Ca2+ channels seem to be of special importance as qPCR revealed a steady increase in Cav3.2 transcript levels over age, e.g. in the cochlea and spiral ganglion neurons (SGN). Furthermore, pharmacological studies suggested an association between Cav3.2 expression and both age-related and noise-induced hearing loss. Given the potential functional relevance of Cav3.2 VGGCs in sensorineural hearing loss, we recorded gender specific auditory evoked brainstem responses (ABRs) upon both click and tone burst presentation. Here we present auditory brainstem response (ABR) data from Cav3.2+/+, Cav3.2+/- and Cav3.2-/- mice from both genders which are of value for researchers who want to evaluate how Cav3.2 loss affects basic auditory parameters, e.g. click and tone burst based hearing thresholds, amplitude growth function and peak latencies. Data description: Information presented here includes ABR data from age-matched female and male Cav3.2+/+, Cav3.2+/- and Cav3.2-/- mice and technical aspects of the auditory recording protocol. Data were recorded using a commercially available ABR setup from Tucker Davis Technologies Inc. (TDT). Raw data files (arf.-file format) were exported as txt.-files with free access for analysis.

Inherited hearing loss is associated with gene mutations that result in sensory hair cell (HC) malfunction. HC structure is defined by the cytoskeleton, which is mainly composed of actin filaments and actin-binding partners. LIM motif-containing protein kinases (LIMKs) are the primary regulators of actin dynamics and consist of two members: LIMK1 and LIMK2. Actin arrangement is directly involved in the regulation of cytoskeletal structure and the maturation of synapses in the central nervous system, and LIMKs are involved in structural plasticity by controlling the activation of the actin depolymerization protein cofilin in the olfactory system and in the hippocampus. However, the expression pattern and the role of LIMKs in mouse cochlear development and synapse function also need to be further studied. We show here that the Limk genes are expressed in the mouse cochlea. We examined the morphology and the afferent synapse densities of HCs and measured the auditory function in Limk1 and Limk2 double knockout (DKO) mice. We found that the loss of Limk1 and Limk2 did not appear to affect the overall development of the cochlea, including the number of HCs and the structure of hair bundles. There were no significant differences in auditory thresholds between DKO mice and wild-type littermates. However, the expression of p-cofilin in the DKO mice was significantly decreased. Additionally, no significant differences were found in the number or distribution of ribbon synapses between the DKO and wild-type mice. In summary, our data suggest that the Limk genes play a different role in the development of the cochlea compared to their role in the central nervous system.

Based on anatomical connectivity and basic response characteristics, primate auditory cortex is divided into a central core surrounded by belt and parabelt regions. The encoding of pitch, a prototypical element of sound identity, has been studied in primary auditory cortex (A1) but little is known about how it is encoded and represented beyond A1. The caudal auditory belt and parabelt cortical fields process spatial information but also contain information on non-spatial aspects of sounds. In this study, we examined neuronal responses in these areas to pitch-varied marmoset vocalizations, to derive the consequent representation of pitch in these regions and the potential underlying mechanisms, to compare to the encoding and representation of pitch of the same sounds in A1. With respect to response patterns to the vocalizations, neurons in caudal medial belt (CM) showed similar short-latency and short-duration response patterns to A1, but caudal lateral belt (CL) neurons at the same hierarchical level and caudal parabelt (CPB) neurons at a higher hierarchical level showed delayed or much delayed response onset and prolonged response durations. With respect to encoding of pitch, neurons in all cortical fields showed sensitivity to variations in the vocalization pitch either through modulation of spike-count or of first spike-latency. The utility of the encoding mechanism differed between fields: pitch sensitivity was reliably represented by spike-count variations in A1 and CM, while first spike-latency variation was better for encoding pitch in CL and CPB. In summary, our data show that (a) the traditionally-defined belt area CM is functionally very similar to A1 with respect to the representation and encoding of complex naturalistic sounds, (b) the CL belt area, at the same hierarchical level as CM, and the CPB area, at a higher hierarchical level, have very different response patterns and appear to use different pitch-encoding mechanisms, and (c) caudal auditory fields, proposed to be specialized for encoding spatial location, can also contain robust representations of sound identity.

Introduction: There are several key differences between impulse and continuous noise: the nature of the noise itself, the cochlear and neuronal structures affected, the severity to which they damage the auditory system, and the period of time in which damage occurs. Notably, no work on hidden hearing loss after impulse noise exposure has been done to this point, though it has been extensively studied after continuous noise. Hidden hearing loss manifests physiologically with reductions in suprathreshold amplitudes of the first wave of the auditory brainstem response, while auditory thresholds can remain relatively normal. Objective: This study aimed to assess the extent to which, if at all, hidden hearing loss is present after exposure to impulse noise in C57BL6/J mice. Methods: Thirty-one C57BL6/J mice were used in the experiment, in accordance with IACUC protocols. Auditory brainstem responses were recorded before and after noise exposures. The noise exposures consisted of 500 impulses at 137 dB peSPL. Results: Suprathreshold amplitude reductions in the P1 wave of the mouse auditory brainstem response were seen, but only at frequencies with significant threshold shift. Conclusion: These amplitude changes were consistent with hidden hearing loss, and we conclude that impulse noise can cause hidden hearing loss, but future studies are required to determine the specific mechanisms involved and if they parallel those of hidden hearing loss after continuous noise.

Introduction: To detect congenital hearing loss in mice, an objective measure is needed other than mouse behavioral observation. This study aimed to refine the methodology of auditory brainstem response measurement and identify potential congenital hearing loss models in laboratory mouse strains. Methods: Mice were anesthetized and fitted with head electrodes. Each mouse underwent four ABR measurements according to four testing conditions: A - no chamber; conventional tone; B - chamber; conventional tone; C - no chamber; short tone; D - chamber; short tone. Potential congenital hearing loss models were identified using 10 mice from each strain (C57BL, BALB/c, CH3, ICR, and ddY) through sound-attenuated ABR measurements with short-tone bursts. Potential congenital hearing loss models exhibited hearing thresholds ≥30 dB in both ears. Data were analyzed for normal distribution and variance homogeneity using the D'Agostino-Pearson/Kolmogorov-Smirnov and F value tests, respectively. One-way analysis of variance (ANOVA), with the Tukey-Kramer test, was used to conduct parametric analysis, and the Kruskal-Wallis/Friedman test, with a Dunn's test for post hoc analysis, was used to perform non-parametric analysis. Results: The simultaneous use of a sound-attenuating chamber and short-tone bursts provided clearly defined wave patterns, even at lower sound intensities. Inbred strains, especially C57BL/6 sub-strains, constitute suitable congenital hearing loss models. Conclusions: Our study shows that environmental factors should be addressed in animal studies of hearing function. Potential congenital hearing loss models may be found amongst commercially available inbred strains.

Cyclin-dependent kinase 5 (CDK5) is abundantly expressed in post-mitotic cells including neurons. It is involved in multiple cellular events, such as cytoskeletal dynamics, signaling cascades, gene expression, and cell survival, et al. Dysfunction of CDK5 has been associated with a number of neurological disorders. Here we show that CDK5 is expressed in mouse cochlear hair cells, and CDK5 inactivation in hair cells causes hearing loss in mice. CDK5 inactivation has no effect on stereocilia development in the cochlear hair cells. However, it affects stereocilia maintenance, resulting in stereocilia disorganization and eventually stereocilia loss. Consistently, hair cell loss was significantly elevated by CDK5 inactivation. Despite that CDK5 has been shown to play important roles in synapse development and/or function, CDK5 inactivation does not affect the formation of ribbon synapses of cochlear hair cells. Further investigation showed that CDK5 inactivation causes reduced phosphorylation of ERM (ezrin, radixin, and moesin) proteins, which might contribute to the stereocilia deficits. Taken together, our data suggest that CDK5 plays pivotal roles in auditory hair cells, and CDK5 inactivation causes hearing loss in mice.

The primary data are the impulse responses that were recorded in an echoic environment, using a set of twelve loudspeakers and a microphone. They were used as a part of an acoustic calibration process of large environments, as presented by Kazakov and Nelken (DOI: 10.1016/j.jneumeth.2018.08.025; Kazakov and Nelken, 2018). The impulse responses can be also used to localize the microphone in 3D (multi-lateration). The required audio files and the MATLAB code allows a complete reproduction of the experiment.

This data article provides raw auditory evoked brainstem responses (ABRs) from controls and Cav2.3 transgenics, i.e. heterozygous Cav2.3+/- and Cav2.3-/- null mutants. Gender specific ABR recordings were performed in age-matched animals under ketamine/xylazine narcosis. Data presented here include ABRs upon both click and tone burst presentation in the increasing SPL mode using a commercially available ABR setup from Tucker Davis Technologies Inc. (TDT, USA). Detailed information is provided for the sound attenuating cubicle, electrical shielding, electrode parameters, stimulus characteristics and architecture, sampling rate, filtering processes and ABR protocol application during the course of data acquisition and recording. The later are important for subsequent analysis of click and tone burst related hearing thresholds, amplitude growth function and peak latencies. Raw data are available at MENDELEY DATA, DIO: 〈DOI:10.17632/g6ygz2spzx.1〉, URL: 〈https://data.mendeley.com/datasets/g6ygz2spzx/1〉).

The sensory cells that are responsible for hearing include the cochlear inner hair cells (IHCs) and outer hair cells (OHCs), with the OHCs being necessary for sound sensitivity and tuning1. Both cell types are thought to arise from common progenitors; however, our understanding of the factors that control the fate of IHCs and OHCs remains limited. Here we identify Ikzf2 (which encodes Helios) as an essential transcription factor in mice that is required for OHC functional maturation and hearing. Helios is expressed in postnatal mouse OHCs, and in the cello mouse model a point mutation in Ikzf2 causes early-onset sensorineural hearing loss. Ikzf2cello/cello OHCs have greatly reduced prestin-dependent electromotile activity, a hallmark of OHC functional maturation, and show reduced levels of crucial OHC-expressed genes such as Slc26a5 (which encodes prestin) and Ocm. Moreover, we show that ectopic expression of Ikzf2 in IHCs: induces the expression of OHC-specific genes; reduces the expression of canonical IHC genes; and confers electromotility to IHCs, demonstrating that Ikzf2 can partially shift the IHC transcriptome towards an OHC-like identity.

The ability to accurately integrate or bind stimuli from more than one sensory modality is highly dependent on the features of the stimuli, such as their intensity and relative timing. Previous studies have demonstrated that the ability to perceptually bind stimuli is impaired in various clinical conditions such as autism, dyslexia, schizophrenia, as well as aging. However, it remains unknown if adult-onset hearing loss, separate from aging, influences audiovisual temporal acuity. In the present study, rats were trained using appetitive operant conditioning to perform an audiovisual temporal order judgment (TOJ) task or synchrony judgment (SJ) task in order to investigate the nature and extent that audiovisual temporal acuity is affected by adult-onset hearing loss, with a specific focus on the time-course of perceptual changes following loud noise exposure. In our first series of experiments, we found that audiovisual temporal acuity in normal-hearing rats was influenced by sound intensity, such that when a quieter sound was presented, the rats were biased to perceive the audiovisual stimuli as asynchronous (SJ task), or as though the visual stimulus was presented first (TOJ task). Psychophysical testing demonstrated that noise-induced hearing loss did not alter the rats' temporal sensitivity 2-3 weeks post-noise exposure, despite rats showing an initial difficulty in differentiating the temporal order of audiovisual stimuli. Furthermore, consistent with normal-hearing rats, the timing at which the stimuli were perceived as simultaneous (i.e., the point of subjective simultaneity, PSS) remained sensitive to sound intensity following hearing loss. Contrary to the TOJ task, hearing loss resulted in persistent impairments in asynchrony detection during the SJ task, such that a greater proportion of trials were now perceived as synchronous. Moreover, psychophysical testing found that noise-exposed rats had altered audiovisual synchrony perception, consistent with impaired audiovisual perceptual binding (e.g., an increase in the temporal window of integration on the right side of simultaneity; right temporal binding window (TBW)). Ultimately, our collective results show for the first time that adult-onset hearing loss leads to behavioral plasticity of audiovisual perception, characterized by a rapid recalibration of temporal sensitivity but a persistent impairment in the perceptual binding of audiovisual stimuli.

In the adult auditory organ, mechanoelectrical transducer (MET) channels are essential for transducing acoustic stimuli into electrical signals. In the absence of incoming sound, a fraction of the MET channels on top of the sensory hair cells are open, resulting in a sustained depolarizing current. By genetically manipulating the in vivo expression of molecular components of the MET apparatus, we show that during pre-hearing stages the MET current is essential for establishing the electrophysiological properties of mature inner hair cells (IHCs). If the MET current is abolished in adult IHCs, they revert into cells showing electrical and morphological features characteristic of pre-hearing IHCs, including the re-establishment of cholinergic efferent innervation. The MET current is thus critical for the maintenance of the functional properties of adult IHCs, implying a degree of plasticity in the mature auditory system in response to the absence of normal transduction of acoustic signals.