Auditory Research publications

Bilateral cochlear implants (BiCIs) improve spatial-hearing outcomes relative to a single cochlear implant (CI), but the extent varies across patients. One limiting factor may be interaurally asymmetric spectro-temporal representations of sounds. The present study simulated interaural spectro-temporal asymmetries to explore how they affect binaural processing in listeners with normal hearing. We simulated CI stimulation using high-rate (500 pps) band limited acoustic pulse trains with a 3 mm bandwidth and 4 or 6.5 kHz center frequency. Second-order amplitude modulation (AM) was applied at a 100 Hz modulation rate, 20% or 50% modulation depth, and sinusoidal or sawtooth shape. Intracranial lateralization was used to assess utility of whole-waveform interaural time differences (ITDs). Results demonstrated that lateralization of envelope ITDs was limited by the ear with smaller AM depth. This effect depended upon the sharpness of temporal onsets and the extent to which frequencies overlapped in each ear. These results suggest that interaural asymmetry in spectro-temporal representations may limit binaural outcomes of patients with BiCIs. Two well-established models of binaural processing that assume interaural symmetry and rely on coincidence-detection were used to predict performance. Models were mostly predictive of performance, but made consistent errors, suggesting that models of BiCI stimulation using coincidence-detection should be improved to account for asymmetries.

Background: Millions of older adults have age-related hearing loss (ARHL), a disorder where potassium-secreting cells in the cochlea's lateral wall often degenerate. The degeneration reduces the force that drives ions into the sensory cells during sound stimulation, which is traditionally thought to explain the loss of hearing. Here we describe previously unknown mechanisms underlying this metabolic form of ARHL. Methods: Fluorescence spectroscopy and live-cell imaging was used in Dunkin-Hartley guinea pigs of either sex to investigate the effects of lateral wall dysfunction on the hearing organ and its accessory structures. Critical findings were confirmed by studying samples of human temporal bones. Findings: Lateral wall dysfunction caused calcium levels in the inner ear to decline, a change that was most pronounced in the tectorial membrane, an accessory structure crucial for transmitting acoustic stimuli to sensory cell stereocilia. This calcium depletion deprived the sensory cells of an essential ion. Additionally, the tectorial membrane detached from stereocilia, significantly impairing their ability to respond to sound. Sound-evoked responses were further decreased by sustained contraction of the entire hearing organ. Interpretation: These findings establish the tectorial membrane as a key factor in metabolic ARHL, which needs to be considered when developing better diagnostic tools or treatments. Funding: Swedish Research Council grants 2017-06092 and 2022-00548, Swedish Brain foundation grant FO2023-0171 and US National Institutes of Health grant R01DC000141-44.

Speech perception relies on two fundamental acoustic components: spectral and temporal. While spectral information is known to be represented in the auditory cortex through tonotopy, how temporal features are organized has remained unclear. Here, by varying onset rise-ramp steepness and frequencies, we reveal that temporal envelope steepness-a critical cue for phoneme discrimination and sound source perception-is systematically mapped in the mouse auditory cortex. Using widefield calcium imaging, we discovered that the envelope steepness is represented orthogonally to the tonotopic axis, forming a two-dimensional cortical map that mirrors the dual structure of sounds. This organization was observed in primary-like areas but not in higher-order-like areas, indicating distinct auditory processing streams. These findings uncover a principle of cortical organization, suggesting that the auditory cortex encodes sound along two independent axes and thereby provides a neural basis for the parallel processing of complex sounds such as speech and natural acoustic environments.

We recorded responses of single neurons in core and belt auditory cortical fields in alert macaque monkeys to frequency-modulated sounds, key feature of many natural sounds, including speech and vocalizations. We found that the timing of neural activity, rather than its magnitude, explained decoding accuracy in all cortical areas, and we did not observe compelling evidence of improved discriminability in core or belt fields beyond that seen in the primary auditory cortex.

Objective: Screen for differential proteins in the cochlea of mice associated with Age-Related Hearing Loss (ARHL), analyze and validate the expression of specific differential proteins and genes in the cochlea and auditory cortex of ARHL mice, and preliminarily explore their potential mechanisms of action. Methods: ABR (Auditory Brainstem Response) hearing tests were conducted to select 15-month-old C57BL/6 mice with significantly decreased hearing as the experimental group and 2-month-old mice with normal hearing as the control group. Cochleae were dissected, and unlabeled quantitative proteomics was employed to identify and analyze differentially expressed proteins in the inner ear of the two groups of mice. Key node proteins were selected via the STRING database and Cytoscape analysis. The expression of two selected proteins, ApoE and Spp1, in the cochlea was detected using qRT-PCR, Western blot, and immunofluorescence techniques, and their expression in the auditory cortex of the brain was further explored. Results: Label-free quantitative proteomics identified 115 differentially expressed proteins in the cochlea of 15-month-old ARHL mice compared to 2-month-old hearing-normal mice, including 42 upregulated and 73 downregulated proteins. GO and KEGG enrichment analyses revealed significant enrichment of differentially expressed proteins in functions and signaling pathways associated with neurodegenerative diseases and neurotransmission. Protein-Protein Interaction (PPI) analysis using the STRING database and Cytoscape selection identified ApoE and Spp1 as key hub proteins. Validation via qRT-PCR, Western blot, and immunofluorescence demonstrated that both ApoE and Spp1 were highly expressed in the cochlea and auditory cortex of the ARHL mice compare to 2-month-old hearing-normal mice. Conclusion: ApoE and Spp1 are upregulated in the cochlea of ARHL mice, particularly in spiral ganglion neurons, and in the auditory cortex, suggesting their potential involvement in the pathogenesis and progression of ARHL through the modulation of auditory neural conduction systems. Level of evidence: Level 2.

Williams syndrome is a developmental disorder caused by a microdeletion entailing the loss of a single copy of 25–27 genes on chromosome 7q11.23. Patients suffer from cardiovascular and neuropsychological symptoms. Structural abnormalities of the cardiovascular system in Williams syndrome have been attributed to the hemizygous loss of the elastin (ELN) gene. In contrast, the neuropsychological consequences of Williams syndrome, including sensorimotor deficits, hypersociability, and cognitive impairments, have been mainly attributed to altered expression of transcription factors, like LIMK1, GTF2I, and GTF2IRD1, while the potential impact of altered cerebrovascular function has been largely overlooked. To study the relationship between Williams syndrome mutations and vascularization of both the heart and brain, we generated a mouse model carrying a relatively long microdeletion Del(5Ncf1-Fkbp6). Heterozygous Del(5Ncf1-Fkbp6) mice had elongated and tortuous aortas but, unlike Eln haploinsufficient mice, showed no signs of structural cardiac hypertrophy. Remarkably, we also observed structural abnormalities in coronary and brain vessels, including disorganized extracellular matrices. Importantly, the mutant mice faithfully replicated both cardiovascular and neuropsychological symptoms observed in patients. The phenotype was even more comprehensive than in former models, with structure–function correlations evident in aberrant auditory and motor behaviors resembling those in patients with Williams syndrome. Together, our findings suggest that not only cardiovascular but also neuropsychological symptoms in Williams syndrome may be driven in part by vascular abnormalities affecting both heart and brain.

Sensorineural hearing loss (SNHL) is caused mainly by irreversible damage to sensory hair cells after noise exposure, ototoxic medication, and ageing, with men being more prone to developing SNHL than women are. For animal models, sex-related susceptibility to develop SNHL needs to be taken into account. Ototoxic trauma can be modeled in mice via the systemic administration of furosemide and kanamycin. Several other deafening models have shown differences in response to ototoxic medication between female and male mice. Differences in response to kanamycin-induced ototoxicity in male and female mice have not been studied. Here, we examined sex differences in susceptibility to kanamycin plus furosemide-induced ototoxicity in adult C57BL/6 J mice. Adult (postnatal day 40) female and male C57BL/6 J and Lgr5GFP (C57BL/6 J background) mice were used. The animals were deafened with a single dose of furosemide (100 mg/kg, i.v.) in combination with kanamycin (700 or 900 mg/kg, s.c.). Before deafening, seven and twenty-eight days after deafening, auditory brainstem responses (ABRs) to click stimuli were recorded to evaluate hearing performance. The cochleae were harvested seven or twenty-eight days after the induction of ototoxicity and processed for histology to evaluate hair cell loss. Male mice presented large ABR threshold shifts after ototoxic treatment with 700 mg/kg kanamycin (50 dB median hearing loss). In males, 9/12 mice had threshold shifts greater than 40 dB. However, female mice presented significantly less hearing loss in response to 700 mg/kg kanamycin, as observed via ABRs after ototoxic treatment (32 dB median hearing loss), and only 8/22 female mice presented threshold shifts greater than 40 dB. When treated with 900 mg/kg kanamycin, female mice presented large ABR threshold shifts after ototoxic treatment (50 dB median), and 11/16 mice presented threshold shifts greater than 40 dB. Female C57BL/6 J mice are less susceptible to kanamycin-induced hearing loss than males are and hence need higher doses of kanamycin to reach the same level of hearing loss. This finding is in line with the prevalence of disabling hearing loss in humans, which is 7.3% in males and 4.8% in females, where estrogens have been linked to increased hearing performance and protection against hearing loss.

Introduction Bilateral cochlear implants (BiCIs) do not restore sound localization abilities to the full extent exhibited by typical hearing (TH) listeners, partly due to poor encoding of interaural time differences (ITDs). ITD cues have been provided and investigated using synchronized research processors that ensure the precise delivery of ITD cues. These studies have been conducted in a direct stimulation setting, which bypasses the processor microphones and, in most cases, removes interaural level difference cues (ILDs). To our knowledge, this is the first study that evaluated the efficacy of synchronized stimulation in restoring sensitivity to ITDs in a free field localization experiment. This was made possible by the CCi-MOBILE, a portable and real-time processing research platform that allows for synchronizing microphone inputs. Methods Fourteen BiCI listeners were tested with experimental real-time coding strategies in comparison to unsynchronized clinical processors. We calculated the binaural cues from the acoustic stimuli at the level of microphone input. Results The recordings show that the experimental coding strategies in this study deliver ITDs with greater precision than the clinical strategy. However, psychophysical testing did not show the benefit of an ITD-encoding strategy in improving localization in a free field. The ITD encoding strategies preserved ITDs, which better differentiated unique loudspeaker locations than interaural level differences (ILDs), suggesting that listeners could achieve improved performance if they accessed these cues. As expected, ILDs were similar across all strategies, including the ITD encoding strategies. The lack of improvement in localization performance is likely because ILDs remained to be the dominant cue in acute localization testing, even when ITD cues were available. Discussion Providing BiCI listeners with adequate experiences with ITD cues may be necessary to shift their reliance from ILD dominance to a combined reliance on ILD and ITD cues in free-field conditions. The CCi-MOBILE could enable take-home practice with novel stimulation strategies for extended experiences and long-term evaluation in real-world listening environments.

Previous studies based on layer specificity suggest that ascending signals from the thalamus to the sensory neocortex preserve spatially organized information, but it remains unknown whether sensory information descending from sensory neocortex to the thalamus also maintains such spatial organization pattern. By focusing on projection specificity, we mapped the tone response properties of two groups of cortical neurons in the primary auditory cortex (A1), based on the relationship between their specific connections to other regions and their function in ascending (thalamocortical recipient [TR] neurons) or descending (corticothalamic [CT] neurons) auditory information. A clear tonotopic gradient was observed among TR neurons, but not CT neurons. Additionally, CT neurons exhibited markedly higher heterogeneity in their frequency tuning and had broader bandwidth than TR neurons. These results reveal that the information flow descending from A1 to the thalamus via CT neurons is not arranged tonotopically, suggesting that the descending information flow possibly contributes to higher-order feedback processing of diverse auditory inputs.

Early studies on orientation selectivity in the visual cortex have suggested that sensory systems generate new feature representations at specific processing stages. Many observations challenge this view, but in the absence of systematic, multistage measurements, the logic of how feature tuning emerges remains elusive. Here, using a generic approach based on representational similarity analysis with a noise-corrected population metric, we demonstrate in the mouse auditory system that feature representations evolve gradually with, in some cases, major, feature-specific improvements at particular stages. We observe that single frequency tuning is already fully developed in the cochlear nucleus, the first stage of processing, while tuning to higher-order features improves up to the auditory cortex, with major steps in the inferior colliculus for amplitude modulation frequency or noise bandwidth tuning and in the cortex for frequency modulation direction and for complex sound identity or direction. Moreover, we observe that intensity tuning is established in a feature-dependent manner, earlier for pure frequencies than for more complex sounds. This indicates that auditory feature computations are a mix of stepwise and gradual processes which together contribute to decorrelate sound representations.

The role of P2X4, one of the most abundant ionotropic purinergic receptors in the central nervous system, is explored in the context of auditory function. We observed, by using constitutive and conditional P2X4mCherryIN knock-in adult mouse models of either sex, a specific high expression of mCherry-tagged P2X4 in living cochlear outer hair cells (OHCs), from immature postnatal stages to adulthood. This P2X4-mCherry expression, confirmed by confocal immunofluorescence microscopy in wild-type (WT) mice, was mainly concentrated in the intracellular apical region of OHCs, in the area of Hensen's body, a lysosomal-rich region, specifically labeled with the fluorescent dye lysotracker. In addition, the basal cholinergic efferent synaptic region of the OHCs was found to express P2X4 at the cell membrane. Surprisingly, the assessment of the hearing function in constitutive P2X4 knock-out (P2X4KO) mice showed improved auditory brainstem responses (ABRs) with smaller latencies and lower thresholds. These P2X4KO mice, as well as conditional Myo15-Cre:P2X4KO mice, displayed enhanced distortion product otoacoustic emissions (DPOAEs), suggesting an improved electromechanical “amplification” activity by OHCs. These mutant animals showed reduced inhibition of DPOAEs by contralateral noise, consistent with a weaker inhibitory effect of the medial cholinergic olivocochlear (MOC) efferent circuit on OHCs. When P2X4KO mice were exposed to noise (white noise 95 dB SPL, 12 h), ABRs decreased and partially recovered much like WT mice, but DPOAEs showed faster recovery. We concluded that the MOC negative feedback modulation of cochlear micromechanics, in addition to involve Ca 2+ permeable α9/α10 nicotinic receptors, also requires the activation of postsynaptic P2X4 receptors in OHCs.

We describe here a mode of activity of neurons in auditory cortex of freely moving rats consisting of large, slow firing rate modulations, which were not driven by sounds, were larger than the sound evoked responses, and were locked to specific time points during the task, similar to responses of hippocampal time-sensitive neurons. This activity mode had important functional consequences to sound processing during task performance. We show that the slow firing rate modulations caused the ongoing activity just before sound presentations to be higher during task performance than during passive listening. Concurrently, during task performance, the responses to target stimuli were weaker but more informative about the task-relevant sounds. In a model, higher ongoing activity caused more synaptic depression of the cortico-cortical synapses, reducing the tendency of the network to produce population spikes and resulting in weaker but more informative responses to sounds.

Autism is an early‐onset neurodevelopmental disorder characterized by restricted, repetitive behaviors and atypical patterns of social communication and interaction. A considerable proportion of autistic individuals experience divergent auditory perception, which can interfere with their ability to navigate everyday sound environments. Auditory brainstem responses are electrophysiological potentials elicited by auditory stimuli that evaluate neural activity along the auditory nerve and brainstem. Importantly, the auditory brainstem response varies by sex, with females typically showing higher amplitudes and shorter latencies than males. This sex‐specific neurophysiological profile is especially relevant in autism research, where the male‐to‐female diagnosis ratio is approximately 3:1. Thus, exploring the neurobiological mechanisms underlying sex‐specific variations in autistic traits is essential. Furthermore, autism sensory profiles may vary based on the independent and mutual effects of environmental and genetic factors. To deepen this understanding, we examined auditory brainstem responses in two rat models of autism: the GRIN2B rare mutation model and the prenatal valproic acid induction model, alongside control animals. We assessed peak amplitudes and latencies (Waves I through V), inter‐peak intervals (I–III, I–V, and III–V), and amplitude ratios (III:I, V:I, and V:III). Female rats generally exhibited greater amplitudes and longer latencies across waveforms. Regarding rat models, control animals consistently showed larger amplitudes and shorter latencies compared to autism‐like models. Exploratory analyses further suggested pairwise interactions between sex and rat model, indicating modulation of auditory phenotypes linked to autism. Thus, our findings reveal key insights into the effects of sex and rat model, as well as their interactions.

Hearing relies upon speedy synaptic transmission of sound information from inner hair cells (IHCs) to spiral ganglion neurons. To accomplish this, IHCs use a sophisticated presynaptic machinery including the multi-C 2 domain protein otoferlin that is affected by human deafness mutations. Otoferlin is essential for IHC exocytosis, but how it binds Ca 2+ and the target membrane to serve synaptic vesicle (SV) tethering, docking, and fusion remained unclear. Here, we obtained cryo–electron microscopy structures of otoferlin and employed molecular dynamics simulations of membrane binding. We show that membrane binding by otoferlin involves C 2 B-C 2 G domains and repositions C 2 F and C 2 G domains. Disruption of Ca 2+ -binding sites of the C 2 D domain in mice altered synaptic sound encoding and eliminated the Ca 2+ cooperativity of IHC exocytosis, indicating that it requires the binding of several Ca 2+ -ions by otoferlin. Together, our findings elucidate molecular mechanisms underlying otoferlin-mediated SV docking and support the role of otoferlin as Ca 2+ sensor of SV fusion in IHCs.

Fragile X Syndrome (FXS) is a leading genetic cause of intellectual disability and autism-like behaviors. Glutamatergic mGluR5 receptors and matrix metalloproteinase-9 (MMP-9) are therapeutic targets to treat FXS, but clinical trials targeting each of these pathways have not been successful. Here, we tested if the electroencephalography (EEG) phenotypes associated with FXS are reversed with a novel combination of treatments affecting the two pathways. Fmr1 knockout (KO) mice were given 10 days of CTEP (mGluR5 antagonist) alone or in combination with minocycline (MMP-9 inhibitor). EEG was recorded during resting (no acoustic stimulation) and during sound presentations (to produce sound-evoked EEG) at 1 day and 10 days after the beginning of treatment administration to test acute effects and potential tachyphylaxis. In pre-treatment WT and KO mice comparisons, we replicated previously published Fmr1 KO mouse EEG phenotypes including elevated power in the resting gamma band, elevated single trial power, and reduced phase-locking to spectrotemporally dynamic auditory stimuli. We found that CTEP treatment alone did not show any benefit compared to vehicle in Fmr1 KO mice after either 1 or 10 days of treatment. CTEP + minocycline reduced resting gamma band power in the Fmr1 KO mice to a greater extent than vehicle at both treatment time points. There were no effects on sound-evoked responses. These data suggest that combined CTEP and minocycline treatment alters resting EEG measures while each treatment administered separately does not yield similar changes. High power in broadband gamma frequency correlates with irritability, stereotyped behaviors, and hyperactivity in FXS patients, suggesting a combination of drugs that reduce mGluR5 and MMP-9 activity may be beneficial in FXS.

Adolescence is a developmental period characterized by heightened plasticity. Yet, how ongoing development affects sensory processing and cognitive function is unclear. We investigated how adolescent (postnatal day 20–42) and adult (postnatal day 60–82) mice differ in performance on a pure tone Go/No-Go auditory discrimination task of varying difficulty. Using dense electrophysiological recordings, we measured spiking activity at single neuron resolution in the auditory cortex while mice were engaged in the task. As compared to adults, adolescent mice showed lower auditory discrimination performance in a difficult task. This difference in performance was due to higher response variability and weaker cognitive control expressed as higher lick bias. Adolescent and adult neuronal responses differed only slightly in representations of pure tones when measured outside the context of learning and the task. However, cortical representations after learning within the context of the task were markedly different. We found differences in stimulus- and choice-related activity at the single neuron level representations, as well as lower population-level decoding of the difficult task in adolescents. Overall, cortical decoding in adolescents was lower and slower, especially for difficult sound discrimination, reflecting immature cortical representations of sounds and choices. Notably, we found age-related differences, which were more pronounced after learning, reflecting the combined impact of age and learning. Our findings highlight distinct neurophysiological and behavioral profiles in adolescence, underscoring the ongoing development of cognitive control mechanisms and cortical plasticity during this sensitive developmental period.

The pre‐hearing mouse cochlea undergoes critical periods of spontaneous Ca 2+ ‐dependent activity that spreads across non‐sensory supporting cells and inner hair cells (IHCs). These signals have been shown to regulate not only the refinement of neural circuits along the auditory pathway towards functional maturity, but also the maturation of the hair cells into sensory receptors. Although the origin and interplay of these Ca 2+ signals during cochlear development have recently been investigated in live mice, the impact of anaesthesia on in vivo functional measurements was not explored. Here, we investigate the effects of different anaesthetic regimes (ketamine and xylazine; 2.5% isoflurane; and 1.0%–1.5% isoflurane with the sedative acepromazine) that provided an effective unconsciousness to perform the surgery and Ca 2+ ‐imaging recordings from the intact cochlea of live mice. The IHCs, supporting cells and spiral ganglion neuron terminals onto the IHCs showed spontaneous Ca 2+ ‐dependent activity under all anaesthetic regimes, with a few significant differences observed between conditions. Calcium waves from supporting cells synchronized the activity of IHCs. Moreover, we found that the endocochlear potential, which is crucial for cochlear function, was unaffected by the different anaesthetics. However, low concentrations of isoflurane produced the most stable recordings of vital physiological signs in mice, including heart rate and breathing rate. Although all anaesthetic regimes tested appeared to be suitable for performing Ca 2+ imaging from the cochlea of pre‐hearing live mice, a low concentration of isoflurane (1.0%–1.5%), combined with the pre‐anaesthetic sedative acepromazine and oxygenation, represents the most suitable approach to maintain a stable and long‐lasting depth of anaesthesia.

Discrimination of sensory stimuli is fundamentally constrained by the information encoded in neuronal responses. In the barn owl, interaural time difference (ITD) serves as a primary cue for azimuthal sound localization and is represented topographically in the midbrain auditory space map in the external nucleus of the inferior colliculus (ICx). While prior studies have demonstrated a correspondence between spatial tuning and behavioral acuity, it remains unclear how changes in sensory reliability influence this relationship. Here, we examined how behavioral and neuronal ITD discrimination thresholds vary with binaural correlation (BC), which manipulates ITD cue reliability. Using the pupil dilation response as a behavioral metric in head-fixed owls of either sex, we found that ITD just-noticeable differences increased exponentially as BC decreased. In contrast, the widths of ICx ITD tuning curves increased more modestly, indicating that tuning resolution alone does not account for behavioral discrimination performance. By computing the Fisher information from ICx neuronal responses, we showed that the average neuronal discriminability predicts behavioral thresholds across BC values. A habituation-based model incorporating BC-dependent changes in tuning width, firing rate, and response variability successfully accounted for both direction and ITD discrimination. These findings support a model in which perceptual acuity is governed by the combined influence of neuronal tuning and variability and provide a unified framework for understanding how midbrain auditory representations underlie adaptive spatial hearing.

The ability to pick out and attend to one sound in a noisy mixture underpins successful communication in many natural scenarios. Selective attention has been shown to drastically alter sound encoding in the cortex and has been hypothesized to modulate subcortical processing via an extensive efferent network. The body of work investigating this possibility in humans has not resulted in a clear consensus, possibly owing to limitations in the available methodologies. Here, we used new experimental tools that allowed distinct neural responses from across the auditory pathway to be simultaneously acquired from human listeners attending to the sound of one person talking while ignoring a second. Our series of experiments provide convergent evidence that selective attention does not influence sound encoding in the auditory periphery or brainstem, with an effect first appearing in the cortex. Humans’ ability to focus their attention on a single sound even in the presence of many others is as remarkable as it is essential. These findings add needed clarity regarding the mechanisms that make this feat possible.

Exposure to loud and/or prolonged noise damages the cochlea and triggers downstream brain changes, resulting in hearing loss and altered speech comprehension. It remains unclear however whether noise exposure also compromises the cochlear efferent system; a feedback pathway originates in the brain that fine-tunes hearing sensitivity in the cochlea. Recent evidence suggests that lateral olivocochlear (LOC) efferent system supports hearing recovery by sustaining auditory nerve activity for several weeks after acoustic trauma (Sitko et al., 2025); however, the underlying neural mechanisms have not been fully elucidated. To address this gap, we examined the long-term effects of noise-induced hearing loss (NIHL) on the spontaneous action potential (AP) firing pattern in mouse LOC neurons of either sex. Under normal conditions, these neurons display a characteristic burst firing pattern driven by Ca 2+ channel-mediated membrane voltage oscillations. One week following noise exposure, hearing thresholds were significantly elevated, and the duration of AP bursts was increased, as a result of an enhanced Ca 2+ current. Moreover, LOC neurons exhibit Ca 2+ -dependent inactivation (CDI) of Ca 2+ currents—a key process that shapes the duration of voltage oscillations—whose properties were also modified following noise exposure. Interestingly, our data suggest that the interplay between Ca 2+ channel activation, CDI, and outward leak currents is sufficient to sustain the oscillating behavior of LOC neurons. We propose that NIHL increases efferent activity, thereby enhancing the release of neurotransmitters and neuropeptides, which may support long-lasting restoration of sensory coding in the damaged cochlea.