Auditory Research publications

Background: Sensory impairments commonly occur in patients with autism or intellectual disability. Fragile X syndrome (FXS) is one form of intellectual disability that is often comorbid with autism. In electroencephalographic (EEG) recordings obtained from humans with FXS, the ability of cortical regions to consistently synchronize, or "phase-lock", to modulated auditory stimuli is reduced compared to that of typically developing individuals. At the same time, less time-locked, "non-phase-locked" power induced by sounds is higher. The same changes occur in the Fmr1 knockout (KO) mouse - an animal model of FXS. We determined if Fmr1 deletion in a subset of brainstem auditory neurons plays any role in these EEG changes in the mouse. Methods: We reinstated FMRP expression in a subpopulation of brainstem auditory neurons in an otherwise Fmr1 KO control (conditional on; cON Fmr1) mouse and used EEG recordings to determine if reinstatement normalized, or "rescued", the phase-locking phenotype observed in the cON Fmr1 mouse. In determining rescue, this also meant that Fmr1 deletion in the same neuron population was necessary for the phenotype to occur. Results: We find that Fmr1 reinstatement in a subset of brainstem neurons rescues certain aspects of the phase-locking phenotype but does not rescue the increase in non-phase-locked power. Unexpectedly, not all electrophysiological phenotypes observed in the Fmr1 KO were observed in the cON Fmr1 mouse used for the reinstatement experiments, and this was likely due to residual expression of FMRP in these Fmr1 KO controls. Conclusions: Fmr1 deletion in brainstem neurons is necessary for certain aspects of the decreased phase-locking phenotype in the Fmr1 KO, but not necessary for the increase in non-phase-locked power induced by a sound. The most likely brainstem structure underlying these results is the inferior colliculus. We also demonstrate that low levels of FMRP can rescue some EEG phenotypes but not others. This latter finding provides a foundation for how symptoms in FXS individuals may vary due to FMRP levels and that reinstatement of low FMRP levels may be sufficient to alleviate particular symptoms.

Hearing depends on precise synaptic transmission between cochlear inner hair cells and spiral ganglion neurons through afferent ribbon synapses. Neuroligins (Nlgns) facilitate synapse maturation in the brain, but they have gone unstudied in the cochlea. We report Nlgn3 and Nlgn1 knockout (KO) cochleae have fewer ribbon synapses and have impaired hearing. Nlgn3 KO is more vulnerable to noise trauma with limited activity at high frequencies one day after noise. Furthermore, Nlgn3 KO cochleae have a 5-fold reduction in synapse number compared to wild type after two weeks of recovery. Double KO cochlear phenotypes are more prominent than the KOs, for example, 5-fold smaller synapses, 25% reduction in synapse density, and 30% less synaptic output. These observations indicate Nlgn3 and Nlgn1 are essential to cochlear ribbon synapse maturation and function.

Background: Cryopyrin-associated periodic syndrome (CAPS) is an inherited autoinflammatory disease caused by a gain-of-function mutation in NLRP3. Although CAPS patients frequently suffer from sensorineural hearing loss, it remains unclear whether CAPS-associated mutation in NLRP3 is associated with the progression of hearing loss. Methods: We generated a mice with conditional expression of CAPS-associated NLRP3 mutant (D301N) in cochlea-resident CX3CR1 macrophages and examined the susceptibility of CAPS mice to inflammation-mediated hearing loss in a local and systemic inflammation context. Findings: Upon lipopolysaccharide (LPS) injection into middle ear cavity, NLRP3 mutant mice exhibited severe cochlear inflammation, inflammasome activation and hearing loss. However, this middle ear injection model induced a considerable hearing loss in control mice and inevitably caused an inflammation-independent hearing loss possibly due to ear tissue damages by injection procedure. Subsequently, we optimized a systemic LPS injection model, which induced a significant hearing loss in NLRP3 mutant mice but not in control mice. Peripheral inflammation induced by a repetitive low dose of LPS injection caused a blood-labyrinth barrier disruption, macrophage infiltration into cochlea and cochlear inflammasome activation in an NLRP3-dependent manner. Interestingly, both cochlea-infiltrating and -resident macrophages contribute to peripheral inflammation-mediated hearing loss of CAPS mice. Furthermore, NLRP3-specific inhibitor, MCC950, as well as an interleukin-1 receptor antagonist significantly alleviated systemic LPS-induced hearing loss and inflammatory phenotypes in NLRP3 mutant mice. Interpretation: Our findings reveal that CAPS-associated NLRP3 mutation is critical for peripheral inflammation-induced hearing loss in our CAPS mice model, and an NLRP3-specific inhibitor can be used to treat inflammation-mediated sensorineural hearing loss. Funding: National Research Foundation of Korea Grant funded by the Korean Government and the Team Science Award of Yonsei University College of Medicine.

Actb c–g Actg1 –/– mice expressing only γ-actin from an edited Actb c–g allele have growth and survival defects despite expressing normal levels of γ-actin. Cell and auditory phenotypes associated with Actg1 KO were rescued by γ-actin expression from Actb c–g . We conclude that Actb and Actg support unique nucleotide- and protein-dependent functions.

Maternal infections during pregnancy are linked with an increased risk for disorders like Autism Spectrum Disorder and schizophrenia in the offspring. Although precise mechanisms are still unclear, clinical and preclinical evidence suggest a strong role for maternal immune activation (MIA) in the neurodevelopmental disruptions caused by maternal infection. Previously, studies using the Polyinosinic:Polycytidylic (Poly I:C) MIA preclinical model showed that cytokines like Interleukin 6 (Il6) are important mediators of MIA's effects. In this study, we hypothesized that Il15 may similarly act as a mediator of Poly I:C MIA, given its role in the antiviral immune response. To test this hypothesis, we induced Poly I:C MIA at gestational day 9.5 in wildtype (WT) and Il15 -/- rat dams and tested their offspring in adolescence and adulthood. Poly I:C MIA and Il15 knockout produced both independent and synergistic effects on offspring behaviour. Poly I:C MIA decreased startle reactivity in adult WT offspring but resulted in increased adolescent anxiety and decreased adult locomotor activity in Il15 -/- offspring. In addition, Poly I:C MIA led to genotype-independent effects on locomotor activity and prepulse inhibition. Finally, we showed that Il15 -/- offspring exhibit distinct phenotypes that were unrelated to Poly I:C MIA including altered startle reactivity, locomotion and signal transduction in the auditory brainstem. Overall, our findings indicate that the lack of Il15 can leave offspring either more or less susceptible to Poly I:C MIA, depending on the phenotype in question. Future studies should examine the contribution of fetal versus maternal Il15 in MIA to determine the precise developmental mechanisms underlying these changes.

High-intensity sound or blast-induced hearing impairment is a common injury for Service members. Epidemiology studies revealed that the blast-induced hearing loss is associated with the traumatic brain injury (TBI), but the mechanisms of the formation and prevention of auditory injuries require further investigation. Liraglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist, has been reported as a potential treatment strategy for TBI-caused memory deficits; however, there is no study on therapeutics of GLP-1R for blast-induced hearing damage. This paper reports our current study on progressive hearing damage after repeated exposures to low-level blasts in the animal model of chinchilla and the mitigation of hearing damage using liraglutide. Chinchillas were divided into three groups (N = 7 each): blast control, pre-blast treatment, and post-blast treatment. All animals were exposed to six consecutive blasts at the level of 3-5 psi (21-35 kPa) on Day 1. The auditory brainstem response (ABR) was measured on Day 1 (pre- and post-blast) and Days 4, 7, and 14 after blast exposure. Upon the completion of the experiment on Day 14, the brain tissues of animals were harvested for immunofluorescence studies. Significant damage was revealed in blast-exposed chinchillas by increased ABR thresholds, decreased ABR wave I amplitudes, and cell apoptosis in the inferior colliculus in the blast control chinchillas. Treatment with liraglutide appeared to reduce the severity of blast-induced hearing injuries as observed from the drug-treated chinchillas comparing to the blast controls. This study bridges the gap between TBI and hearing impairment and suggests a possible intervention for blast-induced hearing loss for Service members.

Environmental exposure to heavy metal lead, a public health hazard in many post-industrial cities, causes hearing impairment upon long-term exposure. Lead-induced cochlear and vestibular dysfunction is well-documented in animal models. Although short-term exposure to lead at concentrations relevant to environmental settings does not cause significant shifts in hearing thresholds in adults, moderate- to low-level lead exposures induce neuronal damage and synaptic dysfunction. We reported that lead exposure induces oxidative stress in the mouse cochlea. However, lead-induced nitrative stress and potential damage to cochlear ribbon synapses are yet to be fully understood. Therefore, this study has evaluated cochlear synaptopathy and nitrative stress in young-adult mice exposed to 2 mM lead acetate for 28 days. Inductively coupled plasma mass spectrometry (ICP-MS) analysis indicated that this exposure significantly increased the blood lead levels. Assessment of hair cell loss by immunohistochemistry analysis and outer hair cell (OHC) activity by recording distortion product otoacoustic emissions (DPOAEs) indicated that the structure and function of the hair cells were not affected by lead exposure. However, this exposure significantly decreased the expression of C-terminal-binding protein-2 (CtBP2) and GluA2, pre- and post-synaptic protein markers in the inner hair cell synapses, particularly in the basal turn of the organ of Corti, suggesting lead-induced disruption of ribbon synapses. In addition, lead exposure significantly increased the nitrotyrosine levels in spiral ganglion cells, suggesting lead-induced nitrative stress in the cochlea. Collectively, these findings suggest that lead exposure even at levels that do not affect the OHCs induces cochlear nitrative stress and causes cochlear synaptopathy.

Low-frequency interaural time differences and high-frequency interaural level differences (ILDs) are used to localize sounds in the horizontal plane. Older listeners appear to be worse at horizontal-plane sound localization to compared younger listeners, but little is understood about age-related changes to across-frequency binaural processing. This study investigated if the frequency dependence of across-frequency ILD processing is altered for older compared to younger listeners, which was done by using an across-frequency binaural interference task (when the interaural difference sensitivity for a target sound is decreased by a spectrally remote interfering sound with zero interaural differences). It was hypothesized that as listeners experience advancing age and age-related high-frequency hearing loss (i.e., presbycusis), they will demonstrate worse binaural performance and experience more across-channel binaural interference (because of age-related temporal processing deficits), and will increasingly be affected by interferers at lower frequencies (because of age-related hearing loss) when compared to younger listeners. There were 11 older (>65 yrs) and 20 younger (<30 yrs) listeners with normal to near-normal audiometric thresholds up to 2 kHz. They were tested using a left-right ILD lateralization discrimination task. Single-tone ILD discrimination thresholds and across-frequency binaural interference were measured at 0.5, 1, 2, 4, and 8 kHz. ILD thresholds and interference were about twice as large for older compared to younger listeners. Interferers ≤1 kHz produced 2–3 times as much across-frequency binaural interference for older compared to younger listeners. Hearing thresholds were significant predictors of single-tone ILD thresholds; in addition, both target and interferer hearing thresholds were significant predictors of binaural interference. The results suggest a reweighting of binaural information that occurs with advancing age and age-related high-frequency hearing loss. This evidence of plasticity may help explain some of the age-related changes in spatial-hearing abilities.

Deer mice (genus Peromyscus) are an emerging model for aging studies due to their longevity relative to rodents of similar size. Although Peromyscus species are well-represented in genetic, developmental, and behavioral studies, relatively few studies have investigated auditory sensitivity in this genus. Given the potential utility of Peromyscus for investigations of age-related changes to auditory function, we recorded auditory brainstem responses (ABRs) in two Peromyscus species, P. californicus, and P. leucopus, across the lifespan. We compared hearing sensitivity and ABR wave metrics measured in these species with measurements from Mus musculus (CBA/CaJ strain) to assess age-related effects on hearing across species. Recordings in young animals showed that all species had similar hearing ranges and thresholds with peak sensitivity ranging from 8 to 16 kHz; however, P. californicus and P. leucopus were more sensitive to frequencies below 8 kHz. Although M. musculus showed significant threshold shifts across a broad range of frequencies beginning at middle age and worsening among old individuals, older Peromyscus mice retained good sensitivity to sound across their lifespan. Middle-aged P. leucopus had comparable thresholds to young for frequencies below 24 kHz. P. leucopus also had notably large ABRs that were robust to age-related amplitude reductions, although response latencies increased with age. Old P. californicus were less sensitive to mid-range tones (8-16 kHz) than young individuals; however, there were no significant age-effects on ABR amplitudes or latencies in this species. These results indicate that longevity in Peromyscus mice may be correlated with delayed aging of the auditory system and highlight these species as promising candidates for longitudinal hearing research.

A common challenge in neuroscience is how to decompose noisy, multi-source signals measured in experiments into biophysically interpretable components. Analysis of cortical surface electrical potentials (CSEPs) measured using electrocorticography arrays (ECoG) typifies this problem. We hypothesized that high frequency (70-1,000 Hz) CSEPs are composed of broadband (i.e., power-law) and bandlimited components with potentially differing biophysical origins. In particular, the high-gamma band (70-150 Hz) has been shown to be highly predictive for encoding and decoding behaviors and stimuli. Despite its demonstrated importance, whether high-gamma is composed of a bandlimited signal is poorly understood. To address this gap, we recorded CSEPs from rat auditory cortex and demonstrate that the evoked CSEPs are composed of multiple distinct frequency components, including high-gamma. We then show, using a novel robust regression method, that at fast timescales and on single trials during speech production, human high-gamma amplitude cannot be explained by a modulating power-law component; thus, high-gamma is band-limited. Furthermore, we show that the power-law component is less predictive of produced speech compared to the raw high-gamma amplitude. Finally, we show that the largest variance component of human ECoG signals is low-frequency and band-limited, not broadband. Together these results demonstrate that there are multiple, band-limited components of high frequency power in cortical surface electrical potentials, including the high-gamma band, which may have different biophysical origins. Significance Statement Electrocortigraphy (ECoG) records cortical surface electrical potentials (CSEPs). ECoG is utilized in both humans and animal models to understand distributed cortical processing and for brain machine interfaces. The spectral structure of evoked CSEPs is greatly debated. To address this issue, we recorded from rat auditory cortex using µ ECoG and human ventral sensory-motor cortex during speech production with high-density ECoG. Using novel analytic approaches, we found that evoked CSEPs are composed of multiple band-limited components, including high-gamma. These results contrast with the dominant thinking in the field that the high-frequency power in ECoG is broadband. Our results raise the possibility that distinct frequency components of ECoG are biomarkers of processing in different cortical layers.

Several recent preclinical studies have reported that dynamic changes in miRNA expression contribute to hearing function. This study aims to investigate miRNA expression changes in the cochlear nuclei (CN) of rats following chronic noise exposure. Eight-week-old rats (n = 14) were exposed to noise for 4 weeks. The control rats (n = 14) were raised under identical conditions without noise. Two months after noise exposure, the auditory brainstem response (ABR) was examined, and the cochlea and CN were harvested. In the CN, the expression levels of arc, neurocan, and brevican were measured (n = 6 per group). Furthermore, the expression levels of miRNAs and their predicted target genes were measured in the CN (n = 8 per group). ABR thresholds were elevated after 4 weeks of noise exposure, which were maintained for 3 months. In CN, the protein expression of arc and brevican was higher in the noise-exposed group than in the control group (0.95 [standard deviation (SD) = 0.53] vs. 3.19 [SD = 1.00], p < 0.001 for arc and 1.02 [SD = 0.10] vs. 1.66 [SD = 0.24], p < 0.001 for brevican). The noise-exposed rats exhibited lower expression levels of miR-758-5p, miR-15b-5p, miR-212-3p, miR-199a-5p, and miR-134-3p than the control rats (all p < 0.001). The AMPK signaling pathway was predicted to be regulated by these miRNAs. The predicted target genes AKT3, SIRT1, and PRKAA1 were highly expressed in noise-exposed rats. In CN of noise-exposed rats, the miRNAs of miR-758-5p, miR-15b-5p, miR-212-3p, miR-199a-5p, and miR-134-3p were reduced and related to AMPK signaling including AKT3 and SIRT1 expression. These modulation of signaling pathways could mediate the increased expression of brevican in the CN of noise-exposed rats.

Cortical feedback has long been considered crucial for the modulation of sensory perception and recognition. However, previous studies have shown varying modulatory effects of the primary auditory cortex (A1) on the auditory response of subcortical neurons, which complicate interpretations regarding the function of A1 in sound perception and recognition. This has been further complicated by studies conducted under different brain states. In the current study, we used cryo-inactivation in A1 to examine the role of corticothalamic feedback on medial geniculate body (MGB) neurons in awake marmosets. The primary effects of A1 inactivation were a frequency-specific decrease in the auditory response of most MGB neurons coupled with an increased spontaneous firing rate, which together resulted in a decrease in the signal-to-noise ratio. In addition, we report for the first time that A1 robustly modulated the long-lasting sustained response of MGB neurons, which changed the frequency tuning after A1 inactivation, e.g. some neurons are sharper with corticofugal feedback and some get broader. Taken together, our results demonstrate that corticothalamic modulation in awake marmosets serves to enhance sensory processing in a manner similar to center-surround models proposed in visual and somatosensory systems, a finding which supports common principles of corticothalamic processing across sensory systems.

Understanding computational principles in hierarchically organized sensory systems requires functional parcellation of brain structures and their precise targeting for manipulations. Although brain atlases are widely used to infer area locations in the mouse neocortex, it has been unclear whether stereotaxic coordinates based on standardized brain morphology accurately represent functional domains in individual animals. Here, we used intrinsic signal imaging to evaluate the accuracy of area delineation in the atlas by mapping functionally-identified auditory cortices onto bregma-based stereotaxic coordinates. We found that auditory cortices in the brain atlas correlated poorly with the true complexity of functional area boundaries. Inter-animal variability in functional area locations predicted surprisingly high error rates in stereotaxic targeting with atlas coordinates. This variability was not simply attributed to brain sizes or suture irregularities but instead reflected differences in cortical geography across animals. Our data thus indicate that functional mapping in individual animals is essential for dissecting cortical area-specific roles with high precision.

The nucleus reuniens (RE) is necessary for memories dependent on the interaction between the medial prefrontal cortex (mPFC) and hippocampus (HPC). One example is trace eyeblink conditioning, in which the mPFC exhibits differential activity to neutral conditioned stimuli (CS) depending on their contingency with an aversive unconditioned stimulus (US). To test if this relevancy signal is routed to the RE, we photometrically recorded mPFC axon terminals within the RE and tracked their changes with learning. As a comparison, we measured prefrontal terminal activity in the mediodorsal thalamus (MD), which lacks connectivity with the HPC. In naïve male rats, prefrontal terminals within the RE were not strongly activated by tone or light. As the rats associated one of the stimuli (CS+) with the US, terminals gradually increased their response to the CS+ but not the other stimulus (CS-). In contrast, stimulus-evoked responses of prefrontal terminals within the MD were strong even before conditioning. They also became augmented only to the CS+ in the first conditioning session; however, the degree of activity differentiation did not improve with learning. These findings suggest that associative learning selectively increased mPFC output to the RE, signaling the behavioral relevance of sensory stimuli.

Background Susceptibility to noise varies dramatically between mice of the same genetic background; however, the underlying molecular mechanism remains unknown. Methods C57BL/6J (B6) mice of the same sex, age, and strain were exposed to noise of the same intensity and duration, and the auditory brainstem response (ABR) threshold was determined 48 h later. Some mice had significant hearing loss, while some did not; the ABR threshold measured in these two groups of mice was significantly different. The cochlea of the two groups of mice was dissected, and RNA sequencing and analysis were performed. Differentially expressed genes (DEGs) between the two groups were selected, Kyoto Encyclopedia of Genes and Genomes pathway analysis was performed, and protein–protein interaction network maps were listed. Results This study showed that noise exposure of the same intensity and duration caused different degrees of hearing loss in C57BL/6J (B6) mice. This was the result of the up-regulation or down-regulation of many genes, such as Nop2, Bysl, Rrp9, Spsb1, Fbxl20, and Fbxo31. Changes in the transcriptome of these genes may affect cochlear susceptibility to noise. Conclusion The DEGs identified in this experiment may provide more insight into protocols for gene therapy in the clinical practice of hearing loss.

The inferior colliculus (IC) is at the midpoint of the auditory system and integrates virtually all information ascending from the auditory brainstem, organizes it, and transmits the results to the auditory forebrain. Its abundant, excitatory local connections are crucial for this task. This study describes a long duration sound (LDS)-induced potentiation in the IC that changes both subsequent tone-evoked responses and spontaneous activity. Afterdischarges, changes of spontaneous spiking following an LDS, were seen previously in single neurons. Here, we used multi-channel probes to record activity before and after a single, tetanic sound and describe the changes in a population of IC neurons. Following a 60 s narrowband-noise stimulation, a subset of recording channels (∼16%) showed afterdischarges. A facilitated response spike rate to tone pips following an LDS was also observed in ∼16% of channels. Both channels with an afterdischarge and channels with facilitated tone responses had higher firing rates in response to LDS, and the magnitude of the afterdischarges increased with increased responses to the LDS. This is the first study examining the effect of LDS stimulation on tone-evoked responses. This observed facilitation in vivo has similarities to post-tetanic potentiation in vitro as both manner of induction (strong stimulation for several seconds) as well as time-course of the facilitation (second to minute range) are comparable. Channels with and without facilitation appear to be intermixed and distributed widely in the central nucleus of IC, and this suggests a heretofore unknown property of some IC neurons or their circuits. Consequently, this sound-evoked facilitation may enhance the sound-evoked output of these neurons, while, simultaneously, most other IC neurons have reduced or unchanged output in response to the same stimulus.

Noise induced synaptopathy (NIS) has been researched extensively since a large amount of synaptic loss without permanent threshold shift (PTS) was found in CBA mice after a brief noise exposure. However, efforts to translate these results to humans have met with little success—and might not be possible since noise exposure used in laboratory animals is generally different from what is experienced by human subjects in real life. An additional problem is a lack of morphological data and reliable functional methods to quantify loss of afferent synapses in humans. Based on evidence for disproportionate synaptic loss for auditory nerve fibers (ANFs) with low spontaneous rates (LSR), coding-in-noise deficits (CIND) have been speculated to be the major difficulty associated with NIS without PTS. However, no robust evidence for this is available in humans or animals. This has led to a re-examination of the role of LSR ANFs in signal coding in high-level noise. The fluctuation profile model has been proposed to support a role for high-SR ANFs in the coding of high-level noise in combination with efferent control of cochlear gain. This study aimed to induce NIS by a low-level, intermittent noise exposure mimicking what is experienced in human life and examined the impact of the NIS on temporal processing under masking. It also evaluated the role of temporal fluctuation in evoking efferent feedback and the effects of NIS on this feedback.

Exposure to nontraumatic noise in vivo drives long-lasting changes in auditory nerve synapses, which may influence hearing, but the induction mechanisms are not known. We mimicked activity in acute slices of the cochlear nucleus from mice of both sexes by treating them with high potassium, after which voltage-clamp recordings from bushy cells indicated that auditory nerve synapses had reduced EPSC amplitude, quantal size, and vesicle release probability (P r). The effects of high potassium were prevented by blockers of nitric oxide (NO) synthase and protein kinase A. Treatment with the NO donor, PAPA-NONOate, also decreased P r, suggesting NO plays a central role in inducing synaptic changes. To identify the source of NO, we activated auditory nerve fibers specifically using optogenetics. Strobing for 2 h led to decreased EPSC amplitude and P r, which was prevented by antagonists against ionotropic glutamate receptors and NO synthase. This suggests that the activation of AMPA and NMDA receptors in postsynaptic targets of auditory nerve fibers drives release of NO, which acts retrogradely to cause long-term changes in synaptic function in auditory nerve synapses. This may provide insight into preventing or treating disorders caused by noise exposure.SIGNIFICANCE STATEMENT Auditory nerve fibers undergo long-lasting changes in synaptic properties in response to noise exposure in vivo, which may contribute to changes in hearing. Here, we investigated the cellular mechanisms underlying induction of synaptic changes using high potassium and optogenetic stimulation in vitro and identified important signaling pathways using pharmacology. Our results suggest that auditory nerve activity drives postsynaptic depolarization through AMPA and NMDA receptors, leading to the release of nitric oxide, which acts retrogradely to regulate presynaptic neurotransmitter release. These experiments revealed that auditory nerve synapses are unexpectedly sensitive to activity and can show dramatic, long-lasting changes in a few hours that could affect hearing.

Neurons that process sensory information exhibit bursts of electrical activity during development, providing early training to circuits that will later encode similar features of the external world. In the mammalian auditory system, this intrinsically generated activity emerges from the cochlea prior to hearing onset, but its role in maturation of auditory circuitry remains poorly understood. We show that selective disruption of cochlear supporting cell spontaneous activity suppressed patterned burst firing of central auditory neurons without impacting cell survival or acoustic thresholds. However, neurons within the inferior colliculus of these mice exhibited enhanced acoustic sensitivity and broader frequency tuning, resulting in wider isofrequency lamina. Despite this enhanced neural responsiveness, total tone-responsive regions of the midbrain and cortex were substantially smaller. Thus, loss of pre-hearing cochlear activity causes profound changes in neural encoding of sound, with important implications for restoration of hearing in individuals that experience disrupted activity during this critical developmental period.

Electrophysiological oscillations in the brain have been shown to occur as multicycle events, with onset and offset dependent on behavioral and cognitive state. To provide a baseline for state-related and task-related events, we quantified oscillation features in resting-state recordings. We developed an open-source wavelet-based tool to detect and characterize such oscillation events (OEvents) and exemplify the use of this tool in both simulations and two invasively-recorded electrophysiology datasets: one from human, and one from nonhuman primate (NHP) auditory system. After removing incidentally occurring event-related potentials (ERPs), we used OEvents to quantify oscillation features. We identified ∼2 million oscillation events, classified within traditional frequency bands: δ, θ, α, β, low γ, γ, and high γ. Oscillation events of 1–44 cycles could be identified in at least one frequency band 90% of the time in human and NHP recordings. Individual oscillation events were characterized by nonconstant frequency and amplitude. This result necessarily contrasts with prior studies which assumed frequency constancy, but is consistent with evidence from event-associated oscillations. We measured oscillation event duration, frequency span, and waveform shape. Oscillations tended to exhibit multiple cycles per event, verifiable by comparing filtered to unfiltered waveforms. In addition to the clear intraevent rhythmicity, there was also evidence of interevent rhythmicity within bands, demonstrated by finding that coefficient of variation of interval distributions and Fano factor (FF) measures differed significantly from a Poisson distribution assumption. Overall, our study provides an easy-to-use tool to study oscillation events at the single-trial level or in ongoing recordings, and demonstrates that rhythmic, multicycle oscillation events dominate auditory cortical dynamics.