Auditory Neurophysiology publications

Coordinated functioning of the two cortical hemispheres is crucial for perception. The human auditory cortex (ACx) shows functional lateralization with the left hemisphere specialized for processing speech, whereas the right analyzes spectral content. In mice, virgin females demonstrate a left-hemisphere response bias to pup vocalizations that strengthens with motherhood. However, how this lateralized function is established is unclear. We developed a widefield imaging microscope to simultaneously image both hemispheres of mice to bilaterally monitor functional responses. We found that global ACx topography is symmetrical and stereotyped. In both male and virgin female mice, the secondary auditory cortex (A2) in the left hemisphere shows larger responses than right to high-frequency tones and adult vocalizations; however, only virgin female mice show a left-hemisphere bias in A2 in response to adult pain calls. These results indicate hemispheric bias with both sex-independent and -dependent aspects. Analyzing cross-hemispheric functional correlations showed that asymmetries exist in the strength of correlations between DM-AAF and A2-AAF, while other ACx areas showed smaller differences. We found that A2 showed lower cross-hemisphere correlation than other cortical areas, consistent with the lateralized functional activation of A2. Cross-hemispheric activity correlations are lower in deaf, otoferlin knockout (OTOF −/− ) mice, indicating that the development of functional cross-hemispheric connections is experience dependent. Together, our results reveal that ACx is topographically symmetric at the macroscopic scale but that higher-order A2 shows sex-dependent and independent lateralized responses due to asymmetric intercortical functional connections. Moreover, our results suggest that sensory experience is required to establish functional cross-hemispheric connectivity.

Peripheral sensory organ damage leads to compensatory cortical plasticity that is associated with a remarkable recovery of cortical responses to sound. The precise mechanisms that explain how this plasticity is implemented and distributed over a diverse collection of excitatory and inhibitory cortical neurons remain unknown. After noise trauma and persistent peripheral deficits, we found recovered sound-evoked activity in mouse A1 excitatory principal neurons (PNs), parvalbumin- and vasoactive intestinal peptide-expressing neurons (PVs and VIPs), but reduced activity in somatostatin-expressing neurons (SOMs). This cell-type-specific recovery was also associated with cell-type-specific intrinsic plasticity. These findings, along with our computational modelling results, are consistent with the notion that PV plasticity contributes to PN stability, SOM plasticity allows for increased PN and PV activity, and VIP plasticity enables PN and PV recovery by inhibiting SOMs.

The auditory cortex (AC) modulates the activity of upstream pathways in the auditory brainstem via descending (corticofugal) projections. This feedback system plays an important role in the plasticity of the auditory system by shaping response properties of neurons in many subcortical nuclei. The majority of layer (L) 5 corticofugal neurons project to the inferior colliculus (IC). This corticocollicular (CC) pathway is involved in processing of complex sounds, auditory-related learning, and defense behavior. Partly due to their location in deep cortical layers, CC neuron population activity patterns within neuronal AC ensembles remain poorly understood. We employed two-photon imaging to record the activity of hundreds of L5 neurons in anesthetized as well as awake animals. CC neurons are broader tuned than other L5 pyramidal neurons and display weaker topographic order in core AC subfields. Network activity analyses revealed stronger clusters of CC neurons compared to non-CC neurons, which respond more reliable and integrate information over larger distances. However, results obtained from secondary auditory cortex (A2) differed considerably. Here CC neurons displayed similar or higher topography, depending on the subset of neurons analyzed. Furthermore, specifically in A2, CC activity clusters formed in response to complex sounds were spatially more restricted compared to other L5 neurons. Our findings indicate distinct network mechanism of CC neurons in analyzing sound properties with pronounced subfield differences, demonstrating that the topography of sound-evoked responses within AC is neuron-type dependent.

Insufficient sleep is commonplace in modern lifestyle and can lead to grave outcomes, yet the changes in neuronal activity accumulating over hours of extended wakefulness remain poorly understood. Specifically, which aspects of cortical processing are affected by sleep deprivation (SD), and whether they also affect early sensory regions, remain unclear. Here, we recorded spiking activity in the rat auditory cortex along with polysomnography while presenting sounds during SD followed by recovery sleep. We found that frequency tuning, onset responses, and spontaneous firing rates were largely unaffected by SD. By contrast, SD decreased entrainment to rapid (≥20 Hz) click trains, increased population synchrony, and increased the prevalence of sleep-like stimulus-induced silent periods, even when ongoing activity was similar. Recovery NREM sleep was associated with similar effects as SD with even greater magnitude, while auditory processing during REM sleep was similar to vigilant wakefulness. Our results show that processes akin to those in NREM sleep invade the activity of cortical circuits during SD, even in the early sensory cortex.

The P2 component of the auditory evoked potential is commonly thought to reflect acoustic stimulus properties as well as prior exposure to the materials, rather than change-related cortical activity. Here, we challenge this view by showing that the P2 is strongly increased in response to voice pitch changes with a stepwise pattern compared to changes in dynamic pitch contours typical for natural speech, and also reflects the magnitude of these pitch changes. Furthermore, it is demonstrated that neither the P2 nor any other component are affected by the harmonicity of the materials. Despite no prior exposure, artificially created inharmonic versions of the speech materials elicited similar activity throughout auditory cortex. This suggests that so-called harmonic template neurons observed in animal studies are either absent or do not exist in sufficient number in human auditory cortex to detect their activity extracranially. Crucially, both morphology and source reconstructions of the EEG data showed that the P2 appears to consist of two separate subcomponents. Whereas source activity for the “P2a” was strongest in right auditory cortex, the subsequent “P2b” included generators spread across auditory cortex and association areas, bilaterally. The two subcomponents thus likely reflect processing at different stages of the auditory pathway.

Intrinsically generated neural activity propagates through the developing auditory system to promote maturation and refinement of sound processing circuits prior to hearing onset. This early patterned activity is induced by non-sensory supporting cells in the organ of Corti, which are highly interconnected through gap junctions containing connexin 26 ( Gjb2 ). Although loss of function mutations in Gjb2 impair cochlear development and are the most common cause of congenital deafness, it is not known if these variants disrupt spontaneous activity and the developmental trajectory of sound processing circuits in the brain. Here, we show in a new mouse model of Gjb2- mediated congenital deafness that cochlear supporting cells adjacent to inner hair cells (IHCs) unexpectedly retain intercellular coupling and the capacity to generate spontaneous activity, exhibiting only modest deficits prior to hearing onset. Supporting cells lacking Gjb2 elicited coordinated activation of IHCs, leading to coincident bursts of activity in central auditory neurons that will later process similar frequencies of sound. Despite alterations in the structure of the sensory epithelium, hair cells within the cochlea of Gjb2 -deficient mice were intact and central auditory neurons could be activated within appropriate tonotopic domains by loud sounds at hearing onset, indicating that early maturation and refinement of auditory circuits was preserved. Only after cessation of spontaneous activity following hearing onset did progressive hair cell degeneration and enhanced auditory neuron excitability manifest. This preservation of cochlear spontaneous neural activity in the absence of connexin 26 may increase the effectiveness of early therapeutic interventions to restore hearing.

Prediction provides key advantages for survival, and cognitive studies have demonstrated that the brain computes multilevel predictions. Evidence for predictions remains elusive at the neuronal level because of the complexity of separating neural activity into predictions and stimulus responses. We overcome this challenge by recording from single neurons from cortical and subcortical auditory regions in anesthetized and awake preparations, during unexpected stimulus omissions interspersed in a regular sequence of tones. We find a subset of neurons that responds reliably to omitted tones. In awake animals, omission responses are similar to anesthetized animals, but larger and more frequent, indicating that the arousal and attentional state levels affect the degree to which predictions are neuronally represented. Omission-sensitive neurons also responded to frequency deviants, with their omission responses getting emphasized in the awake state. Because omission responses occur in the absence of sensory input, they provide solid and empirical evidence for the implementation of a predictive process.

Humans can easily tune in to one talker in a multitalker environment while still picking up bits of background speech; however, it remains unclear how we perceive speech that is masked and to what degree non-target speech is processed. Some models suggest that perception can be achieved through glimpses, which are spectrotemporal regions where a talker has more energy than the background. Other models, however, require the recovery of the masked regions. To clarify this issue, we directly recorded from primary and non-primary auditory cortex (AC) in neurosurgical patients as they attended to one talker in multitalker speech and trained temporal response function models to predict high-gamma neural activity from glimpsed and masked stimulus features. We found that glimpsed speech is encoded at the level of phonetic features for target and non-target talkers, with enhanced encoding of target speech in non-primary AC. In contrast, encoding of masked phonetic features was found only for the target, with a greater response latency and distinct anatomical organization compared to glimpsed phonetic features. These findings suggest separate mechanisms for encoding glimpsed and masked speech and provide neural evidence for the glimpsing model of speech perception.

This study aimed to evaluate the therapeutic potential of inhibiting protein arginine methyltransferase 5 (PRMT5) in cisplatin-induced hearing loss. The effects of PRMT5 inhibition on cisplatin-induced auditory injury were determined using immunohistochemistry, apoptosis assays, and auditory brainstem response. The mechanism of PRMT5 inhibition on hair cell survival was assessed using RNA-seq and Cleavage Under Targets and Tagment-quantitative polymerase chain reaction (CUT&Tag-qPCR) analyses in the HEI-OC1 cell line. Pharmacological inhibition of PRMT5 significantly alleviated cisplatin-induced damage to hair cells and spiral ganglion neurons in the cochlea and decreased apoptosis by protecting mitochondrial function and preventing the accumulation of reactive oxygen species. CUT&Tag-qPCR analysis demonstrated that inhibition of PRMT5 in HEI-OC1 cells reduced the accumulation of H4R3me2s/H3R8me2s marks at the promoter region of the Pik3ca gene, thus activating the expression of Pik3ca. These findings suggest that PRMT5 inhibitors have strong potential as agents against cisplatin-induced ototoxicity and can lay the foundation for further research on treatment strategies of hearing loss.

Hearing impairment without threshold elevations can occur when there is damage to high‐threshold auditory nerve fibre synapses with cochlear inner hair cells. Instead, cochlear synaptopathy produces suprathreshold deficits, especially in older patients, which affect conversational speech. Given that listening in noise at suprathreshold levels presents significant challenges to the ageing population, we examined the effects of synaptopathy on tone‐in‐noise coding on the central recipients of auditory nerve fibres, i.e. the cochlear nucleus neurons. To induce synaptopathy, guinea pigs received a unilateral sound overexposure to the left ears. A separate group received sham exposures. At 4 weeks post‐exposure, thresholds had recovered but reduced auditory brainstem response wave 1 amplitudes and auditory nerve synapse loss remained on the left side. Single‐unit responses were recorded from several cell types in the ventral cochlear nucleus to pure‐tone and noise stimuli. Receptive fields and rate–level functions in the presence of continuous broadband noise were examined. The synaptopathy‐inducing noise exposure did not affect mean unit tone‐in‐noise thresholds, nor the tone‐in‐noise thresholds in each animal, demonstrating equivalent tone‐in‐noise detection thresholds to sham animals. However, synaptopathy reduced single‐unit responses to suprathreshold tones in the presence of background noise, particularly in the cochlear nucleus small cells. These data demonstrate that suprathreshold tone‐in‐noise deficits following cochlear synaptopathy are evident in the first neural station of the auditory brain, the cochlear nucleus neurons, and provide a potential target for assessment and treatment of listening‐in‐noise deficits in humans. image Key points Recording from multiple central auditory neurons can determine tone‐in‐noise deficits in animals with quantified cochlear synapse damage. Using this technique, we found that tone‐in‐noise thresholds are not altered by cochlear synaptopathy, whereas coding of suprathreshold tones‐in‐noise is disrupted. Suprathreshold deficits occur in small cells and primary‐like neurons of the cochlear nucleus. These data provide important insights into the mechanisms underlying difficulties associated with hearing in noisy environments.

Background Non-invasive recordings of gross neural activity in humans often show responses to omitted stimuli in steady trains of identical stimuli. This has been taken as evidence for the neural coding of prediction or prediction error. However, evidence for such omission responses from invasive recordings of cellular-scale responses in animal models is scarce. Here, we sought to characterise omission responses using extracellular recordings in the auditory cortex of anaesthetised rats. We profiled omission responses across local field potentials (LFP), analogue multiunit activity (AMUA), and single/multi-unit spiking activity, using stimuli that were fixed-rate trains of acoustic noise bursts where 5% of bursts were randomly omitted. Results Significant omission responses were observed in LFP and AMUA signals, but not in spiking activity. These omission responses had a lower amplitude and longer latency than burst-evoked sensory responses, and omission response amplitude increased as a function of the number of preceding bursts. Conclusions Together, our findings show that omission responses are most robustly observed in LFP and AMUA signals (relative to spiking activity). This has implications for models of cortical processing that require many neurons to encode prediction errors in their spike output.

Despite the absence of tympanic middle ears, snakes can hear. They are thought to primarily detect substrate vibration via connections between the lower jaw and the inner ear. We used the western rat snake ( Pantherophis obsoletus ) to determine how vibration is processed in the brain. We measured vibration‐evoked potential recordings to reveal sensitivity to low‐frequency vibrations. We then used tract tracing combined with immunohistochemistry and Nissl staining to describe the central projections of the papillar branch of the VIIIth nerve. Applications of biotinylated dextran amine to the basilar papilla (homologous to the organ of Corti of mammals) labeled bouton‐like terminals in two first‐order cochlear nuclei, a rostrolateral nucleus angularis (NA) and a caudomedial nucleus magnocellularis (NM). NA formed a distinct dorsal eminence, consisted of heterogenous cell types, and was parvalbumin positive. NM was smaller and poorly separated from the surrounding vestibular nuclei. NM was distinguished by positive calbindin label and included fusiform and round cells. Thus, the atympanate western rat snake shares similar first‐order projections to tympanate reptiles. Auditory pathways may be used for detecting vibration, not only in snakes but also potentially in atympanate early tetrapods.

The perception of pitch is a fundamental percept, which is mediated by the auditory system, requiring the abstraction of stimulus properties related to the spectro-temporal structure of sound. Despite its importance, there is still debate as to the precise areas responsible for its encoding, which may be due to species differences or differences in the recording measures and choices of stimuli used in previous studies. Moreover, it was unknown whether the human brain contains pitch neurons and how distributed such neurons might be. Here, we present the first study to measure multiunit neural activity in response to pitch stimuli in the auditory cortex of intracranially implanted humans. The stimulus sets were regular-interval noise with a pitch strength that is related to the temporal regularity and a pitch value determined by the repetition rate and harmonic complexes. Specifically, we demonstrate reliable responses to these different pitch-inducing paradigms that are distributed throughout Heschl’s gyrus, rather than being localized to a particular region, and this finding was evident regardless of the stimulus presented. These data provide a bridge across animal and human studies and aid our understanding of the processing of a critical percept associated with acoustic stimuli.

Alterations in neuronal plasticity and critical periods are common across neurodevelopmental diseases, including Fragile X syndrome (FXS), the leading single-gene cause of autism. Characterized with sensory dysfunction, FXS is the result of gene silencing of Fragile X messenger ribonucleoprotein 1 (FMR1) and loss of its product, Fragile X messenger ribonucleoprotein (FMRP). The mechanisms underlying altered critical period and sensory dysfunction in FXS are obscure. Here, we performed genetic and surgical deprivation of peripheral auditory inputs in wildtype and Fmr1 knockout (KO) mice across ages and investigated the effects of global FMRP loss on deafferentation-induced neuronal changes in the ventral cochlear nucleus (VCN) and auditory brainstem responses. The degree of neuronal cell loss during the critical period was unchanged in Fmr1 KO mice. However, the closure of the critical period was delayed. Importantly, this delay was temporally coincidental with reduced hearing sensitivity, implying an association with sensory inputs. Functional analyses further identified early-onset and long-lasting alterations in signal transmission from the spiral ganglion to the VCN, suggesting a peripheral site of FMRP action. Finally, we generated conditional Fmr1 KO (cKO) mice with selective deletion of FMRP in spiral ganglion but not VCN neurons. cKO mice recapitulated the delay in the VCN critical period closure in Fmr1 KO mice, confirming an involvement of cochlear FMRP in shaping the temporal features of neuronal critical periods in the brain. Together, these results identify a novel peripheral mechanism of neurodevelopmental pathogenesis.

Previous work has demonstrated that performance in an auditory selective attention task can be enhanced or impaired, depending on whether a task-irrelevant visual stimulus is temporally coherent with a target auditory stream or with a competing distractor. However, it remains unclear how audiovisual (AV) temporal coherence and auditory selective attention interact at the neurophysiological level. Here, we measured neural activity using EEG while human participants (men and women) performed an auditory selective attention task, detecting deviants in a target audio stream. The amplitude envelope of the two competing auditory streams changed independently, while the radius of a visual disk was manipulated to control the AV coherence. Analysis of the neural responses to the sound envelope demonstrated that auditory responses were enhanced largely independently of the attentional condition: both target and masker stream responses were enhanced when temporally coherent with the visual stimulus. In contrast, attention enhanced the event-related response evoked by the transient deviants, largely independently of AV coherence. These results provide evidence for dissociable neural signatures of bottom-up (coherence) and top-down (attention) effects in AV object formation. SIGNIFICANCE STATEMENT Temporal coherence between auditory stimuli and task-irrelevant visual stimuli can enhance behavioral performance in auditory selective attention tasks. However, how audiovisual temporal coherence and attention interact at the neural level has not been established. Here, we measured EEG during a behavioral task designed to independently manipulate audiovisual coherence and auditory selective attention. While some auditory features (sound envelope) could be coherent with visual stimuli, other features (timbre) were independent of visual stimuli. We find that audiovisual integration can be observed independently of attention for sound envelopes temporally coherent with visual stimuli, while the neural responses to unexpected timbre changes are most strongly modulated by attention. Our results provide evidence for dissociable neural mechanisms of bottom-up (coherence) and top-down (attention) effects on audiovisual object formation.

Sensory systems preferentially strengthen responses to stimuli based on their reliability at conveying accurate information. While previous reports demonstrate that the brain reweighs cues based on dynamic changes in reliability, how the brain may learn and maintain neural responses to sensory statistics expected to be stable over time is unknown. The barn owl’s midbrain features a map of auditory space where neurons compute horizontal sound location from the interaural time difference (ITD). Frequency tuning of midbrain map neurons correlates with the most reliable frequencies for the neurons’ preferred ITD (Cazettes et al., 2014). Removal of the facial ruff led to a specific decrease in the reliability of high frequencies from frontal space. To directly test whether permanent changes in ITD reliability drive frequency tuning, midbrain map neurons were recorded from adult owls, with the facial ruff removed during development, and juvenile owls, before facial ruff development. In both groups, frontally tuned neurons were tuned to frequencies lower than in normal adult owls, consistent with the change in ITD reliability. In addition, juvenile owls exhibited more heterogeneous frequency tuning, suggesting normal developmental processes refine tuning to match ITD reliability. These results indicate causality of long-term statistics of spatial cues in the development of midbrain frequency tuning properties, implementing probabilistic coding for sound localization.

Animals sense sounds through hierarchical neural pathways that ultimately reach higher-order cortices to extract complex acoustic features, such as vocalizations. Elucidating how spectrotemporal integration varies along the hierarchy from primary to higher-order auditory cortices is a crucial step in understanding this elaborate sensory computation. Here we used two-photon calcium imaging and two-tone stimuli with various frequency-timing combinations to compare spectrotemporal integration between primary (A1) and secondary (A2) auditory cortices in mice. Individual neurons showed mixed supralinear and sublinear integration in a frequency-timing combination-specific manner, and we found unique integration patterns in these two areas. Temporally asymmetric spectrotemporal integration in A1 neurons suggested their roles in discriminating frequency-modulated sweep directions. In contrast, temporally symmetric and coincidence-preferring integration in A2 neurons made them ideal spectral integrators of concurrent multifrequency sounds. Moreover, the ensemble neural activity in A2 was sensitive to two-tone timings, and coincident two-tones evoked distinct ensemble activity patterns from the linear sum of component tones. Together, these results demonstrate distinct roles of A1 and A2 in encoding complex acoustic features, potentially suggesting parallel rather than sequential information extraction between these regions.

During development, early-life stress (ELS) impairs cognition, learning, and emotional regulation, in part by disrupting neural circuitry in regions underlying these higher-order functions. In addition, our recent work indicates that ELS also alters simple sensory perception: ELS impaired auditory perception and neural encoding of short gaps in sounds, which are essential for vocal communication. The combination of higher-order and basic sensory disruption suggests that ELS is likely to affect both the perception and interpretation of communication signals. We tested this hypothesis by measuring behavioral responses to conspecific vocalizations (those emitted by other gerbils) in ELS and untreated Mongolian gerbils. Because stress effects often differ by sex, we separately examined females and males. To induce ELS, pups were intermittently maternally separated and restrained from post-natal days (P) 9–24, a time window when the auditory cortex is most sensitive to external disruption. We measured the approach responses of juvenile (P31–32) gerbils to two types of conspecific vocalizations: an alarm call, which is emitted to alert other gerbils of a potential threat, and the prosocial contact call, which is emitted near familiar gerbils, especially after separation. Control males, Control females, and ELS females approached a speaker emitting pre-recorded alarm calls, while ELS males avoided this source, suggesting that ELS affects the response to alarm calls in male gerbils. During playback of the pre-recorded contact call, Control females and ELS males avoided the sound source, while Control males neither approached nor avoided, and ELS females approached the sound. These differences cannot be accounted for by changes in locomotion or baseline arousal. However, ELS gerbils slept more during playback, suggesting that ELS may reduce arousal during vocalization playback. Further, male gerbils made more errors than females on a measure of working memory, but the sex difference of cognition in this context may stem from novelty aversion rather than impaired memory. These data indicate that ELS influences behavioral responses to ethologically relevant communication sounds in a sex-specific manner, and are among the first to demonstrate an altered response to auditory stimuli following ELS. Such changes may arise from differences in auditory perception, cognition, or a combination of factors, and suggest that ELS may affect auditory communication in human adolescents.

Sensory cortical areas are robustly modulated by higher-order cortices. Our previous study shows that the anterior cingulate cortex (ACC) can immediately and transiently enhance responses in the mouse auditory cortex (ACx). Here, we further examined whether strong activation of ACC neurons can induce long-term effects in mice of both sexes. To our surprise, only stimulation of cell bodies in the ACC, but not ACC-to-ACx terminal activation, induced long-term enhancement of auditory responses in the ACx. Anatomical examination showed that the ACC indirectly projects to the ACx via the rhinal cortex (RCx). High-frequency stimulation of ACC-projecting terminals to the RCx or RCx-projecting terminals to the ACx induced a similar effect as the cell body activation of ACC neurons, whereas silencing the RCx blocked this long-term enhancement. High-frequency stimulation of ACC projections to the RCx also induced long-term augmentation of sound-evoked flight behavior in male mice. These results show that the ACC promotes the long-term enhancement of auditory responses in the ACx through an indirect pathway via the RCx. SIGNIFICANCE STATEMENT In this study, we demonstrate that the anterior part of the anterior cingulate cortex (ACC) evokes long-term enhancement of auditory responses in the auditory cortex (ACx) when it is strongly activated. Importantly, instead of a direct projection, we show that the ACC implements this effect via an indirect pathway through the lateral rhinal cortex using a series of physiological, optogenetic, anatomic, and behavioral experiments. Along with a short-term effect, this long-term enhancement induced by an indirect ACC-to-ACx projection could increase the odds of survival when animals are faced with threats after a significant event.

Exposure to combinations of environmental toxins is growing in prevalence; and therefore, understanding their interactions is of increasing societal importance. Here, we examined the mechanisms by which two environmental toxins, polychlorinated biphenyls (PCBs) and high-amplitude acoustic noise, interact to produce dysfunction in central auditory processing. PCBs are well established to impose negative developmental impacts on hearing. However, it is not known whether developmental exposure to this ototoxin alters the sensitivity to other ototoxic exposures later in life. Here, male mice were exposed to PCBs in utero, and later as adults were exposed to 45 min of high-intensity noise. We then examined the impacts of the two exposures on hearing and the organization of the auditory midbrain using two-photon imaging and analysis of the expression of mediators of oxidative stress. We observed that developmental exposure to PCBs blocked hearing recovery from acoustic trauma. In vivo two-photon imaging of the inferior colliculus (IC) revealed that this lack of recovery was associated with disruption of the tonotopic organization and reduction of inhibition in the auditory midbrain. In addition, expression analysis in the inferior colliculus revealed that reduced GABAergic inhibition was more prominent in animals with a lower capacity to mitigate oxidative stress. These data suggest that combined PCBs and noise exposure act nonlinearly to damage hearing and that this damage is associated with synaptic reorganization, and reduced capacity to limit oxidative stress. In addition, this work provides a new paradigm by which to understand nonlinear interactions between combinations of environmental toxins. SIGNIFICANCE STATEMENT Exposure to common environmental toxins is a large and growing problem in the population. This work provides a new mechanistic understanding of how the prenatal and postnatal developmental changes induced by polychlorinated biphenyls (PCBs) could negatively impact the resilience of the brain to noise-induced hearing loss (NIHL) later in adulthood. The use of state-of-the-art tools, including in vivo multiphoton microscopy of the midbrain helped in identifying the long-term central changes in the auditory system after the peripheral hearing damage induced by such environmental toxins. In addition, the novel combination of methods employed in this study will lead to additional advances in our understanding of mechanisms of central hearing loss in other contexts.