ABR/DPOAE publications

Focused ultrasound (FUS) is a promising noninvasive neuromodulation approach, but whether it can directly activate central auditory neurons in vivo remains unresolved. We applied high-frequency FUS (20 MHz) to the central nucleus of the inferior colliculus (CNIC) in anesthetized guinea pigs while recording electrophysiological responses from the auditory pathway and cochlea. FUS evoked cortical activity through indirect cochlear activation, possibly via skull-mediated mechanical coupling, rather than direct inferior colliculus activation, with ultrasound-evoked compound action potentials predominating in the ipsilateral cochlea. More interestingly, FUS stimulation of the CNIC induced activation of neurons and glial cells in the CNIC and auditory cortex as demonstrated by c-Fos expression, suggesting that FUS stimulation activated the afferent pathway. We also show that FUS engaged the auditory efferent system, likely via medial olivocochlear neurons, producing reduced compound action potential amplitudes, enhanced cochlear microphonics, and persistent effects lasting at least two hours, consistent with long-lasting efferent plasticity. Strikingly, FUS administered before acoustic trauma almost completely prevented noise-induced hearing loss, limiting auditory brainstem response threshold shifts to <10 dB versus ∼60 dB in controls. Gentamicin abolished these physiological and protective effects, implicating medial olivocochlear activation. These findings identify FUS as a potent noninvasive strategy for engaging auditory efferent circuits and protecting against acoustic injury.

Difficulties understanding speech in noise remain a common complaint even among listeners with normal hearing sensitivity, highlighting the need for objective, more effective measures of real-world listening. The goal of this study was to validate the use of a novel, chirped-speech (Cheech) stimulus—continuous, naturally-spoken speech fused with chirps designed to elicit robust auditory evoked potentials—to characterize relationships between speech recognition, listening effort, and auditory neural encoding. Twenty-five normal-hearing adults completed a sentence-recognition task using both original (unmodified) and Cheech-modified AzBio sentence lists in quiet, +3 dB, and −3 dB signal-to-noise ratio (SNR) conditions while neural responses from the brainstem through cortex were recorded simultaneously. Speech recognition remained near ceiling in quiet but declined with decreasing SNR for both original and Cheech stimuli. Compared with clean speech, Cheech-modified speech showed slightly poorer recognition performance as SNR decreased and somewhat higher perceived effort overall. Yet, Cheech was highly effective at evoking auditory responses from the brainstem (auditory brainstem response, ABR) through the cortex (including middle- and late-latency responses, MLR and LLR) even with <5 minutes listening time per condition. Neural responses showed reduced amplitudes and prolonged latencies as SNR decreased. In general, ABR latencies and wave I amplitudes were associated with speech-in-noise recognition performance, whereas cortical responses (MLR Na, Nb, and LLR P1) were associated with subjective workload. These findings show that Cheech-modified speech preserves intelligibility while yielding robust, multilevel neural recordings during sentence perception, offering a promising approach to examine hierarchical auditory processing under ecologically relevant speech-in-noise conditions.

Background: Prolonged exposure to moderate and loud noise is known to impair hearing; however, the safety of long-duration exposure to low-level sound, such as that encountered during everyday conversation, remains unclear. This study aimed to determine the effect of continuous exposure to sound at a 65 dB sound pressure level (SPL) on auditory processing. Methods: Auditory brainstem responses (ABRs) were recorded in C57BL/6 mice before and after a 1 h exposure to a continuous pure tone at 65 dB SPL. Changes in ABR thresholds, wave amplitudes, and latencies were analyzed across frequencies and time points. Correlations between amplitude and latency changes across ABR waves were also assessed. Results: Tone exposure induced a significant, frequency-specific increase in ABR thresholds, with a mean elevation of approximately 6 dB and a maximum shift of 15 dB. Significant reductions in amplitudes and prolongations of latencies were observed in Waves I–III, while Wave V amplitude remained relatively stable. A strong negative correlation between amplitude reduction and latency increase was found in Wave I, which progressively weakened from Wave II to Wave V. These functional changes persisted for up to three hours following exposure before gradually returning to baseline. Conclusions: Prolonged exposure to low-level sound at intensities typical of conversational speech can transiently impair auditory function and alter early neural processing in the auditory pathway. These findings suggest that sound levels commonly considered safe may still pose a risk when exposure is sustained, with implications for understanding hidden hearing loss and improving early diagnostic approaches.

Age-related hearing loss is a global public health issue that impacts the quality of life in the elderly population. Macrophages are the main immune cell population in the cochlea, yet the role in the development and progression of age-related hearing loss is still unclear. This study analyzed single-cell sequencing data from cochlear tissues of C57BL/6J mice across different ages and identified notable increase in CD74 expression in macrophages with aging. Validation revealed that CD74 levels were elevated in the aged cochlea, while macrophage migration inhibitory factor (MIF) levels decreased. MIF was significantly reduced in both senescent HEI-OC1 cells and supernatant. Notably, the senescent HEI-OC1 supernatant stimulated BV2 cells CD74 expression increased. rCD74 significantly upregulated apoptosis-related genes expression levels in HEI-OC1 cells, while decreasing MIF levels. In the co-culture system of scrambled/CD74 - BV2 cells and HEI-OC1 cells, CD74 - BV2 cells markedly reduced the apoptosis-related genes expression in senescent HEI-OC1 cells. MIF could improve the mitochondrial membrane potential of both groups of HEI-OC1 cells, and decreased the TUNEL positive cells significantly. Our findings using the HEI-OC1 cell model reveal that macrophages secrete CD74 into the microenvironment, where it interacts with MIF, reducing local MIF levels. This interaction weakens MIF’s protective effect on senescent HEI-OC1 cells, promoting apoptosis in these auditory cells. This suggests a potential mechanism whereby elevated CD74 in the aging cochlear microenvironment may contribute to the loss of hair cells in vivo . Targeting macrophage CD74 may offer therapeutic potential for preventing and treating age-related hearing loss.

BACKGROUND: Noise-induced hearing loss (NIHL) has been traditionally attributed to outer hair cell (OHC) damage, but synaptic injury at inner hair cell (IHC)–spiral ganglion neuron (SGN) junctions may better explain persistent functional deficits. OBJECTIVE: To test whether IHC ribbon loss and functional synapse loss scale with pathological noise intensity and to define their longitudinal relationship to hearing function. METHODS: A rodent NIHL model was exposed to 100 dB SPL for 2 h or 110 dB SPL for 4 h. Cochleae were immunolabeled for CtBP2 (presynaptic ribbons) and GluA2 (postsynaptic AMPA receptor puncta). Putative functional synapses were quantified as closely apposed CtBP2/GluA2 pairs. Hearing function was assessed longitudinally and correlated with synaptic measures. RESULTS: Both exposure conditions produced graded reductions in IHC ribbon counts and CtBP2/GluA2 pairs, with greater losses after 110 dB/4 h. The number of CtBP2/GluA2 apposed pairs closely tracked preserved hearing function, providing a stronger association with functional outcome than ribbon counts alone. Ribbon loss remained largely stable across post-exposure intervals, whereas functional synapse loss was disproportionately larger at early time points, consistent with transient pre–post misalignment. Over time, CtBP2/GluA2 pairing partially recovered toward levels predicted by surviving ribbons, suggesting re-alignment or reconnection of a subset of remaining synaptic elements. CONCLUSION: Pathological noise intensity drives exposure-dependent IHC synaptopathy in addition to OHC injury. Functional synapse counts (CtBP2/GluA2 pairs) sensitively reflect stored hearing function and indicate a potential post-exposure window for synaptic re-establishment.

It is widely accepted that tinnitus arises from maladaptive neuroplasticity in the central auditory system, which compensates for reduced peripheral input; notably, the loss of inner hair cell (IHC) synapses is considered a key underlying factor. IHC synapses can immediately and permanently degenerate after noise exposure, independent of hair cell loss, whereas the cell bodies and central projections of cochlear neurons can survive for months to years, providing an extended therapeutic window for improving afferent input through synapse regeneration. Using NHPN-1010 (a combination of 2,4-disulfophenyl-N-tert-butylnitrone and N-acetylcysteine), we propose a delayed treatment strategy (≥ 4 weeks after trauma) for noise-induced tinnitus (NIT) in rats. NHPN-1010 enhanced gap-prepulse inhibition of acoustic startle responses-indicative of diminished tinnitus-like deficits-coupled with a concomitant upregulation of GABAergic inhibition in the dorsal cochlear nucleus, relative to vehicle alone (saline). Furthermore, NHPN-1010, compared to saline, led to increased wave-I amplitudes of auditory brainstem responses, the effect accompanied by a corresponding rise in the number of presynaptic ribbons in IHCs. Our findings suggest that NHPN-1010 plays a therapeutic role in NIT by promoting cochlear synaptogenesis and normalizing central auditory signaling.

Prairie voles ( Microtus ochrogaster ) are a semi-fossorial rodent that are an emerging model in social neuroscience. Comparing laboratory-reared and wild-caught individuals is essential for understanding how environmental history shapes neural and sensory traits and for assessing the ecological validity of laboratory findings. Despite this, relatively few studies have taken this approach. We used auditory brainstem responses (ABRs) to compare ABR thresholds and ABR wave characteristics between laboratory-reared and wild-caught prairie voles. ABR recordings show that, similar to other semi-fossorial rodents, M. ochrogaster exhibit a hearing range of 1–46 kHz with peak sensitivity between 8–24 kHz in wild-caught and 8–32 kHz in laboratory-reared voles. However, wild-caught prairie voles displayed significantly lower ABR thresholds at 1, 4, 8, 16, and 24 kHz compared to laboratory-reared prairie voles. There were significant differences in interpeak latency between both tested groups, with laboratory-reared prairie voles showing faster interpeak latency responses than wild-caught voles. However, there were no differences in amplitude ratios between groups. Laboratory-reared prairie voles showed faster normalized latencies and higher relative amplitude of the binaural interaction component (BIC) of the ABR than wild-caught voles. There were no significant differences in ABR thresholds, interpeak latency, amplitude ratio, normalized latency, and relative amplitude between the sexes. These differences in auditory processing support the importance of integrating both wild and captive populations to advance comparative auditory research.

Auditory hypersensitivity is a prominent symptom in Fragile X syndrome (FXS), the most prevalent monogenic cause of autism and intellectual disability. FXS arises through the loss of the protein encoded by the FMR1 (Fragile X Messenger Ribonucleoprotein 1) gene, FMRP, required for normal neural circuit excitability. In the brainstem, FMRP is necessary for normal development of acoustic reactivity, and its loss has been implicated in audiogenic seizures (AGS) in Fmr1 knockout (KO) mice, modeling auditory hypersensitivity and seizures in FXS patients. The present study investigated the correlation between auditory brainstem function and behavioral expression of AGS at the early (postnatal day P20, infancy) and late (P32, juvenile) stages of auditory development in Fmr1 KO mice compared with wildtype (WT) mice, and in both females and males. We tested responsiveness to pure tones of select auditory pathway elements through auditory brainstem responses, and neural synchronization to amplitude envelopes of modulated acoustic stimuli through auditory steady‐state responses. AGS behavior was categorized for severity during 5‐min exposure to loud sound. Expression of the immediate early gene cFos was quantified as a marker for neuronal activity in the inferior colliculus. During infancy, more severe AGS expression in Fmr1 KO mice compared with WT mice was accompanied by increased responsiveness to acoustic stimuli at the level of the superior olivary complex and inferior colliculus, and stronger neural synchronicity in subcortical auditory neurons. Fmr1 KO mice also had higher cFos positive cell counts in the inferior colliculus after exposure to loud sound. With age, both AGS susceptibility and exaggerated acoustic stimulus‐evoked activity in the Fmr1 KO mice subsided. Intriguingly, Fmr1 KO mice displayed an altered developmental profile in both the threshold and amplitude of auditory brainstem response. Our findings support evidence that AGS activity relies upon hyperexcitability in the auditory system, including in the lower brainstem, possibly due to disturbed auditory maturation. Hyper‐synchronization to modulated sounds in subcortical auditory neurons seemed to predict AGS severity. The developmental trajectory of the auditory hyperresponsiveness and hypersynchrony suggests a transient processing alteration underlying heightened AGS susceptibility in Fmr1 KO mice. A better understanding of FXS‐related circuit and behavioral symptoms of auditory processing across development provides the potential to identify therapeutic strategies to achieve auditory function recovery in FXS.

Tinnitus, the perception of a phantom sound, often occurs as a clinical sequela of auditory traumas. However, the underlying mechanisms of tinnitus are largely unknown. In our previous studies, we found more gamma-aminobutyric acid A receptor alpha 1 subunit (GABAAR-α1)-positive cells in the dorsal cochlear nucleus (DCN) after noise exposure, however, we were not able to identify the specific types of DCN cells that up-regulated GABAAR-α1 after the insult. In the current study, we used Nissl staining, Purkinje cell protein 4 (PCP4) and glutamic acid decarboxylase 67 (GAD67) immunolabeling to identify GABAAR-α1-positive cells in the DCN. Each type of GABAAR-α1-positive cells was quantified and statistically analyzed using immunostaining and Nissl staining according to their morphology, size and location in the DCN. GABAAR-α1-positive cartwheel cells, Golgi cells, as well as ML-stellate and vertical cells were confirmed by dual immunolabeling. In the DCN, the most common GABAAR-α1-positive cells were Golgi cells followed by vertical cells and cartwheel cells while very few other cells were GABAAR-α1-positive in all conditions. We found significantly more GABAAR-α1-positive Golgi cells in the DCN of noise-exposed rats without behavioral evidence of tinnitus compared to normal controls and noise-exposed rats with behavioral evidence of tinnitus. This heightened "context-dependent" inhibition may help to maintain a balanced neuronal network, preventing the potential for tinnitus-related hyperactivity in the auditory pathways.

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.

Early sensory experience can exert lasting perceptual consequences. For example, a brief period of auditory deprivation early in life can lead to persistent spatial hearing deficits. Some forms of hearing loss (i.e., conductive; CHL) can distort acoustical cues needed for spatial hearing, which depend on inputs from both ears. We hypothesize that asymmetric acoustic input during development disrupts auditory circuits that integrate binaural information. Here, we identify prolonged maturation of the binaural auditory brainstem in the guinea pig by tracking auditory evoked potentials across development. Using this age range, we induce a reversible unilateral CHL and ask whether behavioral and neural maturation are disrupted. We find that developmental CHL is associated with alterations in a brainstem readout of binaural function, an effect that was not observed in a separate cohort with adult-onset CHL. Startle-based behavioral measures suggest that Early CHL animals exhibit reduced spatial resolution for high-frequency sound sources. Finally, single-unit recordings of auditory midbrain neurons reveal significantly poorer neural acuity to a sound location cue that largely depends on high-frequency sounds. Thus, these findings show that unilateral deprivation can disrupt developing auditory circuits that integrate binaural information and may give rise to lingering spatial hearing deficits.

The preservation of synaptic integrity and physiological activity is pivotal for post-traumatic auditory rehabilitation following acoustic overexposure. Neuritin, a neurotrophic factor that facilitates synapse formation, maturation, and enhanced synaptic transmission, is essential for synapse development. In this study, we established a noise-induced cochlear synaptopathy model in CBA/CaJ mice, revealing a temporal association between endogenous Neuritin expression and synaptic density. Furthermore, administration of recombinant Human Neuritin (rhNeuritin) effectively preserves synaptic density in the cochlear basal turn at 7 days and 14 days following noise exposure. Importantly, it preserves the density of functional synapses (represented by overlapping CtBP2 and GluA2 puncta) and synapse function (indicated by ABR I wave amplitudes), thus diminishing the impairment of auditory function. In addition, rhNeuritin reverses the decrease in phosphorylated extracellular signal-regulated protein kinase 1/2 (p-ERK1/2) levels resulting from noise exposure. By primarily preserving both the number and functionality of synapses in the basal turn, potentially via the induction of ERK1/2 phosphorylation, rhNeuritin mitigated hearing loss. These findings underscore the protective efficacy of rhNeuritin against noise-induced synaptic injury.

Introduction Tinnitus is the perception of non-meaningful sound in the absence of external stimuli. Although tinnitus behavior in animal models is associated with altered central nervous system activity, it is not currently possible to identify tinnitus using neuronal activity alone. In the mouse inferior colliculus (IC), a subpopulation of neurons demonstrates a sustained increase in spontaneous activity after a long-duration sound (LDS). Methods Here, we use the “ LDS test ” to reveal tinnitus-specific differences in sound-evoked plasticity through IC extracellular recordings and the auditory brainstem response (ABR LDS ) in CBA/CaJ mice after sound exposure and behavioral tinnitus assessment. Results Sound-exposed mice showed stronger and shorter tone-evoked responses in the IC compared to unexposed controls, but these differences were not strong predictors of tinnitus. In contrast, in the LDS test, non-tinnitus mice had a significantly stronger suppression in tone-evoked spike rate compared to tinnitus and unexposed control mice. ABR peak amplitudes also revealed robust differences between tinnitus and non-tinnitus mice, with ABR peaks from non-tinnitus mice exhibiting significantly stronger suppression in the LDS test compared to tinnitus and control mice. No significant differences were seen between cohorts in ABR amplitude, latency, wave V:I ratio, wave V:III ratio, I-V intra-peak latency, and I-VI intra-peak latency. We found high-frequency tone stimuli better suited to reveal tinnitus-specific differences for both extracellular IC and ABR recordings. Discussion We successfully used the LDS test to demonstrate that tinnitus-specific differences in sound-evoked plasticity can be shown using both multi-unit near-field recordings in the IC and non-invasive far-field recordings, providing a foundation for future electrophysiological research into the causes and treatment of tinnitus.

Background: Xeroderma pigmentosum (XP) is caused by impaired DNA repair of UV-induced dipyrimidine-photoproducts. XP cells also show impaired repair/removal of ROS or oxidative DNA lesions caused by UV or 4-nitroquinolline 1-oxide (4NQO). Gene profiling indicated that inflammatory response-related genes are significantly upregulated after UV exposure in XP-A model mice. Objective: Since XP cells are in the state of oxidative stress and inflammation, we aimed to search for therapeutic agents from anti-oxidants/anti-inflammatory drugs, that potentially improve XP symptoms. Methods: Several antioxidants were examined for reducing 4NQO-induced oxidative cytotoxicity or UV-induced oxidative DNA damage in XP-A cells. Among them, we focused on melatonin and evaluated its improving effect for Xpa-deficient MEF on UV-induced cytotoxicity and ROS production, and for Xpa-deficient mice on UV-induced skin tumorigenesis and auditory brainstem responses as one of the neurological symptoms. Results: Melatonin and nicotinamide attenuated 4NQO-induced oxidative cytotoxicity. UV-induced intracellular ROS production and cytotoxicity were improved by melatonin for Xpa-deficient MEF. Finally, the administration of melatonin mitigated UV-induced skin inflammation and tumorigenesis and suppressed hearing deterioration in Xpa-deficient mice. Conclusion: Our results show that melatonin could alleviate XP symptoms through its anti-inflammatory and antioxidant properties.

CRISPR-Cas13 systems have therapeutic promise for the precise correction of point mutations in RNA. Using adenosine deaminase acting on RNA (ADAR) effectors, A-I base conversions can be targeted using guide RNAs (gRNAs). We compare the Cas13 effectors PspCas13b and Cas13bt3 for the repair of the gene USH2A , a common cause of inherited retinal disease and Usher syndrome. In cultured cells, we demonstrate up to 80% efficiency for the repair of the common c.11864 G > A and its murine equivalent c.11840 G > A, across different gRNAs and promoters. We develop and characterize a mouse model of Usher syndrome carrying the c.11840 G > A mutation designed for the evaluation of base editors for inherited retinal disease. Finally, we compare Cas13 effectors delivered via AAV for the repair of Ush2a in photoreceptors. Mean RNA editing rates in photoreceptors across different constructs ranged from 0.32% to 2.04%, with greater efficiency in those injected with PspCas13b compared to Cas13bt3 constructs. In mice injected with PspCas13b constructs, usherin protein was successfully restored and correctly localized to the connecting cilium following RNA editing. These results support the development of transcriptome targeting gene editing therapies for retinal disease.

Noise exposure is one of the most common causes of hearing loss and hyperacusis. Studies have shown that noise exposure can induce a cortical gain to compensate for reduced input of the cochlea, which may contribute to the increased sound sensitivity. However, many people with hyperacusis have no measurable cochlear lesion after being exposed to loud sound. In this experiment, we studied the neurological alterations in the cortical and subcortical areas following a prolonged moderate level of noise exposure (84 dB SPL, 8 h/day for 4 weeks) in the laboratory mice. The cochlear function was monitored by auditory brainstem responses (ABRs). The behavioral auditory sensitivity and temporal processing were evaluated using the acoustic startle response (ASR) and gap‐induced prepulse inhibition (gap‐PPI). The central auditory functions were determined by electrophysiological recordings of the inferior colliculus (IC) and the auditory cortex (AC). Our results showed that although there was no significant difference in the ABR thresholds, the noise group showed enhanced ASR and gap‐PPI compared to the control group. Increased neural activity in both the IC and the AC was recorded in the noise‐exposed mice compared to the control group, suggesting a central gain in both the subcortical and cortical regions. The current source density (CSD) analysis of the AC response revealed an increased columnar excitation and reduced corticocortical projection in the noise group, different from the central gain model of noise‐induced hearing loss. Our results suggest that chronic “nondestructive” noise can increase the gain of the central auditory system by altering the balance of auditory thalamocortical and intracortical inputs, which may contribute to the increased sound sensitivity in people with normal hearing.

Neural circuits in the auditory brainstem compute interaural time and intensity differences used to determine the locations of sound sources. These circuits display features that are specialized for these functions. The projection from the ventral cochlear nucleus (VCN) to the medial nucleus of the trapezoid (MNTB) body travels along highly myelinated fibers and terminates in the calyx of Held. This monoinnervating synapse emerges during development as multiple inputs are eliminated. We previously demonstrated that elimination of microglia with a colony stimulating factor-1 inhibitor results in impaired synaptic pruning so that multiple calyceal terminals reside on principal cells of MNTB. This inhibitor also resulted in impaired auditory brainstem responses (ABRs), with elevated thresholds and increased peak latencies. Loss of the microglial fractalkine receptor, CX3CR1, decreased peak latencies in the ABR. The mechanisms underlying these effects are not known. One prominent microglial signaling pathway involved in synaptic pruning and plasticity during development and aging is the C1q-initiated compliment cascade. Here we investigated the classical complement pathway initiator, C1q, in auditory brainstem maturation. We found that C1q expression is detected in the MNTB by the first postnatal week. C1q levels increased with age and were detected within microglia and surrounding the soma of MNTB principal neurons. Loss of C1q did not affect microglia-dependent calyceal pruning. Excitatory and inhibitory synaptic markers in the MNTB and LSO were not altered with C1q deletion. ABRs showed that C1q KO mice had normal hearing thresholds but shortened peak latencies. Altogether this study uncovers the developmental time frame of C1q expression in the sound localization pathway and shows a subtle functional consequence of C1q knockdown.

Homeostatic plasticity, the ability of neurons to maintain their averaged activity constant around a set point value, is thought to account for the central hyperactivity after hearing loss. Here, we investigated the putative role of GABAergic neurotransmission in this mechanism after a noise-induced hearing loss larger than 50 dB in high frequencies in guinea pigs. The effect of GABAergic inhibition is linked to the normal functioning of K + –Cl– co-transporter isoform 2 (KCC2) which maintains a low intracellular concentration of chloride. The expression of membrane KCC2 were investigated before and after noise trauma in the ventral and dorsal cochlear nucleus (VCN and DCN, respectively) and in the inferior colliculus (IC). Moreover, the effect of gabazine (GBZ), a GABA antagonist, was also studied on the neural activity in IC. We show that KCC2 is downregulated in VCN, DCN and IC 3 days after noise trauma, and in DCN and IC 30 days after the trauma. As expected, GBZ application in the IC of control animals resulted in an increase of spontaneous and stimulus-evoked activity. In the noise exposed animals, on the other hand, GBZ application decreased the stimulus-evoked activity in IC neurons. The functional implications of these central changes are discussed.

Medial olivocochlear (MOC) efferents modulate outer hair cell motility through specialized nicotinic acetylcholine receptors to support encoding of signals in noise. Transgenic mice lacking the alpha9 subunits of these receptors (α9KOs) have normal hearing in quiet and noise, but lack classic cochlear suppression effects and show abnormal temporal, spectral, and spatial processing. Mice deficient for both the alpha9 and alpha10 receptor subunits (α9α10KOs) may exhibit more severe MOC-related phenotypes. Like α9KOs, α9α10KOs have normal auditory brainstem response (ABR) thresholds and weak MOC reflexes. Here, we further characterized auditory function in α9α10KO mice. Wild-type (WT) and α9α10KO mice had similar ABR thresholds and acoustic startle response amplitudes in quiet and noise, and similar frequency and intensity difference sensitivity. α9α10KO mice had larger ABR Wave I amplitudes than WTs in quiet and noise. Other ABR metrics of hearing-in-noise function yielded conflicting findings regarding α9α10KO susceptibility to masking effects. α9α10KO mice also had larger startle amplitudes in tone backgrounds than WTs. Overall, α9α10KO mice had grossly normal auditory function in quiet and noise, although their larger ABR amplitudes and hyperreactive startles suggest some auditory processing abnormalities. These findings contribute to the growing literature showing mixed effects of MOC dysfunction on hearing.

The hearing abilities of mammals are impacted by factors such as social cues, habitat, and physical characteristics. Despite being used commonly to study social behaviors, hearing of the monogamous prairie vole (Microtus ochrogaster) has never been characterized. In this study, anatomical features are measured and auditory brainstem responses (ABRs) are used to measure auditory capabilities of prairie voles, characterizing monaural and binaural hearing and hearing range. Sexually naive male and female voles were measured to characterize differences due to sex. It was found that prairie voles show a hearing range with greatest sensitivity between 8 and 32 kHz, binaural hearing across interaural time difference ranges appropriate for their head sizes. No differences are shown between the sexes in binaural hearing or hearing range (except at 1 kHz), however, female voles have increased amplitude of peripheral ABR waves I and II and longer latency of waves III and IV compared to males. The results confirm that prairie voles have a broad hearing range, binaural hearing consistent with rodents of similar size, and differences in amplitudes and thresholds of monaural physiological measures between the sexes. These data further highlight the necessity to understand sex-specific differences in neural processing that may underly variability in responses between sexes.