Hearing instability and abnormal auditory pathways in infants with congenital cytomegalovirus infection: An audiological and radiological single-centre prospective cohort analysis.

INTRODUCTION: This prospective cohort study aims to investigate the hearing dynamics and the changes in the central auditory pathways in infants with congenital cytomegalovirus (cCMV) infection. MATERIALS AND METHODS: cCMV-infected neonates aged ≤3 weeks old were recruited and underwent clinical and laboratory tests to detect viremia and symptomatic infection, hearing examinations at three and six months of age, and radiological imaging of brain auditory pathways using diffusion tensor imaging. RESULTS: From 26 eligible infants (52 ears), we detected symptomatic infection in nine (34.6%), viremia in 14 (14/25; 56.0%) and sensorineural hearing loss (SNHL) in 14 infants (53.8%). We observed 40 ears (76.9%) with unstable hearing thresholds, 17 (42.5%) of which fluctuated. Hearing fluctuation and progressivity were more common in symptomatic infection (66.7% vs. 14.7%, p<0.001; and 38.9% vs. 2.9%, p=0.002; respectively). A substantial proportion of ears had reduced fractional anisotropy (FA) in the medial geniculate body (59.1%), superior olivary nucleus (45.5%), trapezoid body (40.9%), auditory radiation (36.4%) and inferior colliculus (31.8%). Symptomatic infection was associated with an increased FA in the medial geniculate body (mean difference, MD: 0.12; 95% Confidence Intervals, 95%CI: 0.03, 0.22) and viremia in the inferior colliculus (MD: 0.09; 95%CI: 0.02, 0.16). An FA in the inferior colliculus of ≥0.404 had a sensitivity and specificity of 68.8% and 83.3% in predicting viremia (area under the curve 0.823; 95%CI: 0.633, 1.000, p=0.022). CONCLUSION: SNHL along with its fluctuation and progression are common in cCMV-infected infants. cCMV infection may induce structural changes in the central auditory pathway.

Voxelwise analysis of the central hearing pathway in senior dogs reveals changes associated with fractional lifespan.

Presbycusis, or age-related hearing loss, affects both elderly humans and dogs, significantly impairing their social interactions and cognition. In humans, presbycusis involves changes in peripheral and central auditory systems, with central changes potentially occurring independently. While peripheral presbycusis in dogs is well-documented, research on central changes remains limited. Diffusion tensor imaging (DTI) is a useful tool for detecting and quantifying cerebral white matter abnormalities. This study used DTI to explore the central auditory pathway of senior dogs, aiming to enhance our understanding of canine presbycusis. Dogs beyond 75% of their expected lifespan were recruited and screened with brainstem auditory evoked response testing to select dogs without severe peripheral hearing loss. Sixteen dogs meeting the criteria were scanned using a 3 T magnetic resonance scanner. Tract-based spatial statistics was used to analyze the central auditory pathways. A significant negative correlation between fractional lifespan and fractional anisotropy was found in the acoustic radiation, suggesting age-related white matter changes in the central auditory system. These changes, observed in dogs without severe peripheral hearing loss, may contribute to central presbycusis development.

Peripheral and brainstem auditory evaluation in post-COVID-19 individuals.

PURPOSE: The purpose of this study was to investigate the peripheral and central auditory pathways in adult individuals after COVID-19 infection. METHOD: A total of 44 individuals aged between 19 and 58 years, of both genders, post-COVID-19 infection, confirmed by serological tests, with no previous hearing complaints and no risk factors for hearing loss, were assessed. All the participants underwent the following procedures: pure tone audiometry, logoaudiometry, immitanciometry, and Brainstem Auditory Evoked Potentials (BAEP), in addition to answering a questionnaire about auditory symptoms. RESULTS: Thirteen individuals (29.5 %) had some hearing threshold impairment, mainly sensorineural hearing loss. In the BAEP, 18 individuals (40.9 %) presented longer latencies, mainly in waves III and V. According to the questionnaire answers, 3 individuals (9.1 %) reported worsened hearing and 7 (15.9 %) tinnitus that emerged after the infection. As for the use of ototoxic drugs during treatment, 7 individuals (15.9 %) reported their use, of which 5 showed abnormalities in peripheral and/or central auditory assessments. CONCLUSION: Considering the self-reported hearing complaints after COVID-19 infection and the high rate of abnormalities found in both peripheral and central audiological assessments, it is suggested that the new COVID-19 may compromise the auditory system. Due to the many variables involved in this study, the results should be considered with caution. However, it is essential that audiological evaluations are carried out on post-COVID-19 patients in order to assess the effects of the infection in the short, medium, and long term. Future longitudinal investigations are important for a better understanding of the auditory consequences of COVID-19.

Two Independent Response Mechanisms to Auditory Stimuli Measured with Functional Near-Infrared Spectroscopy in Sleeping Infants.

This study investigated the morphology of the functional near-infrared spectroscopy (fNIRS) response to speech sounds measured from 16 sleeping infants and how it changes with repeated stimulus presentation. We observed a positive peak followed by a wide negative trough, with the latter being most evident in early epochs. We argue that the overall response morphology captures the effects of two simultaneous, but independent, response mechanisms that are both activated at the stimulus onset: one being the obligatory response to a sound stimulus by the auditory system, and the other being a neural suppression effect induced by the arousal system. Because the two effects behave differently with repeated epochs, it is possible to mathematically separate them and use fNIRS to study factors that affect the development and activation of the arousal system in infants. The results also imply that standard fNIRS analysis techniques need to be adjusted to take into account the possibilities of multiple simultaneous brain systems being activated and that the response to a stimulus is not necessarily stationary.

The Neural Representation of Binaural Sound Localization Cues Across Different Subregions of the Chicken's Inferior Colliculus.

The sound localization behavior of the nocturnally hunting barn owl and its underlying neural computations is a textbook example of neuroethology. Differences in sound timing and level at the two ears are integrated in a series of well-characterized steps, from brainstem to inferior colliculus (IC), resulting in a topographical neural representation of auditory space. It remains an important question of brain evolution: How is this specialized case derived from a more plesiomorphic pattern? The present study is the first to match physiology and anatomical subregions in the non-owl avian IC. Single-unit responses in the chicken IC were tested for selectivity to different frequencies and to the binaural difference cues. Their anatomical origin was reconstructed with the help of electrolytic lesions and immunohistochemical identification of different subregions of the IC, based on previous characterizations in owl and chicken. In contrast to barn owl, there was no distinct differentiation of responses in the different subregions. We found neural topographies for both binaural cues but no evidence for a coherent representation of auditory space. The results are consistent with previous work in pigeon IC and chicken higher-order midbrain and suggest a plesiomorphic condition of multisensory integration in the midbrain that is dominated by lateral panoramic vision.

Subcortical origin of nonlinear sound encoding in auditory cortex.

A major challenge in neuroscience is to understand how neural representations of sensory information are transformed by the network of ascending and descending connections in each sensory system. By recording from neurons at several levels of the auditory pathway, we show that much of the nonlinear encoding of complex sounds in auditory cortex can be explained by transformations in the midbrain and thalamus. Modeling cortical neurons in terms of their inputs across these subcortical populations enables their responses to be predicted with unprecedented accuracy. By contrast, subcortical responses cannot be predicted from descending cortical inputs, indicating that ascending transformations are irreversible, resulting in increasingly lossy, higher-order representations across the auditory pathway. Rather, auditory cortex selectively modulates the nonlinear aspects of thalamic auditory responses and the functional coupling between subcortical neurons without affecting the linear encoding of sound. These findings reveal the fundamental role of subcortical transformations in shaping cortical responses.

The role of the Ventral Nucleus of the Trapezoid Body in the auditory prepulse inhibition of the acoustic startle reflex.

Cholinergic signaling is essential to mediate the auditory prepulse inhibition (PPI), an operational measure of sensorimotor gating, that refers to the reduction of the acoustic startle reflex (ASR) when a low-intensity, non-startling acoustic stimulus (the prepulse) is presented just before the onset of the acoustic startle stimulus. The cochlear root neurons (CRNs) are the first cells of the ASR circuit to receive cholinergic inputs from non-olivocochlear neurons of the ventral nucleus of the trapezoid body (VNTB) and subsequently decrease their neuronal activity in response to auditory prepulses. Yet, the contribution of the VNTB-CRNs pathway to the mediation of PPI has not been fully elucidated. In this study, we used the immunotoxin anti-choline acetyltransferase (ChAT)-saporin as well as electrolytic lesions of the medial olivocochlear bundle to selectively eliminate cholinergic VNTB neurons, and then assessed the ASR and PPI paradigms. Retrograde track-tracing experiments were conducted to precisely determine the site of lesioning VNTB neurons projecting to the CRNs. Additionally, the effects of VNTB lesions and the integrity of the auditory pathway were evaluated via auditory brain responses tests, ChAT- and FOS-immunohistochemistry. Consequently, we established three experimental groups: 1) intact control rats (non-lesioned), 2) rats with bilateral lesions of the olivocochlear bundle (OCB-lesioned), and 3) rats with bilateral immunolesions affecting both the olivocochlear bundle and the VNTB (OCB/VNTB-lesioned). All experimental groups underwent ASR and PPI tests at several interstimulus intervals before the lesion and 7, 14, and 21 days after it. Our results show that the ASR amplitude remained unaffected both before and after the lesion across all experimental groups, suggesting that the VNTB does not contribute to the ASR. The%PPI increased across the time points of evaluation in the control and OCB-lesioned groups but not in the OCB/VNTB-lesioned group. At the ISI of 50 ms, the OCB-lesioned group exhibited a significant increase in%PPI (p < 0.01), which did not occur in the OCB/VNTB-lesioned group. Therefore, the ablation of cholinergic non-olivocochlear neurons in the OCB/VNTB-lesioned group suggests that these neurons contribute to the mediation of auditory PPI at the 50 ms ISI through their cholinergic projections to CRNs. Our study strongly reinforces the notion that auditory PPI encompasses a complex mechanism of top-down cholinergic modulation, effectively attenuating the ASR across different interstimulus intervals within multiple pathways.

Mixed Representations of Sound and Action in the Auditory Midbrain.

Linking sensory input and its consequences is a fundamental brain operation. During behavior, the neural activity of neocortical and limbic systems often reflects dynamic combinations of sensory and task-dependent variables, and these "mixed representations" are suggested to be important for perception, learning, and plasticity. However, the extent to which such integrative computations might occur outside of the forebrain is less clear. Here, we conduct cellular-resolution two-photon Ca2+ imaging in the superficial "shell" layers of the inferior colliculus (IC), as head-fixed mice of either sex perform a reward-based psychometric auditory task. We find that the activity of individual shell IC neurons jointly reflects auditory cues, mice's actions, and behavioral trial outcomes, such that trajectories of neural population activity diverge depending on mice's behavioral choice. Consequently, simple classifier models trained on shell IC neuron activity can predict trial-by-trial outcomes, even when training data are restricted to neural activity occurring prior to mice's instrumental actions. Thus, in behaving mice, auditory midbrain neurons transmit a population code that reflects a joint representation of sound, actions, and task-dependent variables.

The Dorsal Part of the Anterior Tuberal Nucleus Responds to Auditory Stimulation in Zebrafish (Danio rerio).

The zebrafish, a widely used model in neurobiology, relies on hearing in aquatic environments. Unfortunately, its auditory pathways have mainly been studied in larvae. In this study, we examined the involvement of the anterior tuberal nucleus (AT) in auditory processing in adult zebrafish. Our tract-tracing experiments revealed that the dorsal subdivision of AT is strongly bidirectionally connected to the central nucleus of the torus semicircularis (TSc), a major auditory nucleus in fishes. Immunohistochemical visualization of the ribosomal protein S6 (pS6) phosphorylation to map neural activity in response to auditory stimulation substantiated this finding: the dorsal but not the ventral part of AT responded strongly to auditory stimulation. A similar response to auditory stimulation was present in the TSc but not in the nucleus isthmi, a visual region, which we used as a control for testing if the pS6 activation was specific to the auditory stimulation. We also measured the time course of pS6 phosphorylation, which was previously unreported in teleost fish. After auditory stimulation, we found that pS6 phosphorylation peaked between 100 and 130 min and returned to baseline levels after 190 min. This information will be valuable for the design of future pS6 experiments. Our results suggest an anatomical and functional subdivision of AT, where only the dorsal part connects to the auditory network and processes auditory information.

Complexin-1 enhances ultrasound neurotransmission in the mammalian auditory pathway.

Unlike megabats, which rely on well-developed vision, microbats use ultrasonic echolocation to navigate and locate prey. To study ultrasound perception, here we compared the auditory cortices of microbats and megabats by constructing reference genomes and single-nucleus atlases for four species. We found that parvalbumin (PV)+ neurons exhibited evident cross-species differences and could respond to ultrasound signals, whereas their silencing severely affected ultrasound perception in the mouse auditory cortex. Moreover, megabat PV+ neurons expressed low levels of complexins (CPLX1-CPLX4), which can facilitate neurotransmitter release, while microbat PV+ neurons highly expressed CPLX1, which improves neurotransmission efficiency. Further perturbation of Cplx1 in PV+ neurons impaired ultrasound perception in the mouse auditory cortex. In addition, CPLX1 functioned in other parts of the auditory pathway in microbats but not megabats and exhibited convergent evolution between echolocating microbats and whales. Altogether, we conclude that CPLX1 expression throughout the entire auditory pathway can enhance mammalian ultrasound neurotransmission.

Fast Inhibition Slows and Desynchronizes Mouse Auditory Efferent Neuron Activity.

The encoding of acoustic stimuli requires precise neuron timing. Auditory neurons in the cochlear nucleus (CN) and brainstem are well suited for accurate analysis of fast acoustic signals, given their physiological specializations of fast membrane time constants, fast axonal conduction, and reliable synaptic transmission. The medial olivocochlear (MOC) neurons that provide efferent inhibition of the cochlea reside in the ventral brainstem and participate in these fast neural circuits. However, their modulation of cochlear function occurs over time scales of a slower nature. This suggests the presence of mechanisms that reduce MOC inhibition of cochlear function. To determine how monaural excitatory and inhibitory synaptic inputs integrate to affect the timing of MOC neuron activity, we developed a novel in vitro slice preparation ("wedge-slice"). The wedge-slice maintains the ascending auditory nerve root, the entire CN and projecting axons, while preserving the ability to perform visually guided patch-clamp electrophysiology recordings from genetically identified MOC neurons. The "in vivo-like" timing of the wedge-slice demonstrates that the inhibitory pathway accelerates relative to the excitatory pathway when the ascending circuit is intact, and the CN portion of the inhibitory circuit is precise enough to compensate for reduced precision in later synapses. When combined with machine learning PSC analysis and computational modeling, we demonstrate a larger suppression of MOC neuron activity when the inhibition occurs with in vivo-like timing. This delay of MOC activity may ensure that the MOC system is only engaged by sustained background sounds, preventing a maladaptive hypersuppression of cochlear activity.

Midbrain sensitivity to auditory motion studied with dichotic sweeps of broadband noise.

Many neurons in the central nucleus of the inferior colliculus (IC) show sensitivity to interaural time differences (ITDs), which is thought to be relayed from the brainstem. However, studies with interaural phase modulation of pure tones showed that IC neurons have a sensitivity to changes in ITD that is not present at the level of the brainstem. This sensitivity has been interpreted as a form of sensitivity to motion. A new type of stimulus is used here to study the sensitivity of IC neurons to dynamic changes in ITD, in which broad- or narrowband stimuli are swept through a range of ITDs with arbitrary start-ITD, end-ITD, speed, and direction. Extracellular recordings were obtained under barbiturate anesthesia in the cat. We applied the same analyses as previously introduced for the study of responses to tones. We find effects of motion which are similar to those described in response to interaural phase modulation of tones. The size of the effects strongly depended on the motion parameters but was overall smaller than reported for tones. We found that the effects of motion could largely be explained by the temporal response pattern of the neuron such as adaptation and build-up. Our data add to previous evidence questioning true coding of motion at the level of the IC.

Anatomy of superior olivary complex and lateral lemniscus in Etruscan shrew.

Based on the auditory periphery and the small head size, Etruscan shrews (Suncus etruscus) approximate ancestral mammalian conditions. The auditory brainstem in this insectivore has not been investigated. Using labelling techniques, we assessed the structures of their superior olivary complex (SOC) and the nuclei of the lateral lemniscus (NLL). There, we identified the position of the major nuclei, their input pattern, transmitter content, expression of calcium binding proteins (CaBPs) and two voltage-gated ion channels. The most prominent SOC structures were the medial nucleus of the trapezoid body (MNTB), the lateral nucleus of the trapezoid body (LNTB), the lateral superior olive (LSO) and the superior paraolivary nucleus (SPN). In the NLL, the ventral (VNLL), a specific ventrolateral VNLL (VNLLvl) cell population, the intermediate (INLL) and dorsal (DNLL) nucleus, as well as the inferior colliculus's central aspect were discerned. INLL and VNLL were clearly separated by the differential distribution of various marker proteins. Most labelled proteins showed expression patterns comparable to rodents. However, SPN neurons were glycinergic and not GABAergic and the overall CaBPs expression was low. Next to the characterisation of the Etruscan shrew's auditory brainstem, our work identifies conserved nuclei and indicates variable structures in a species that approximates ancestral conditions.

Neural processing in the primary auditory cortex following cholinergic lesions of the basal forebrain in ferrets.

Cortical acetylcholine (ACh) release has been linked to various cognitive functions, including perceptual learning. We have previously shown that cortical cholinergic innervation is necessary for accurate sound localization in ferrets, as well as for their ability to adapt with training to altered spatial cues. To explore whether these behavioral deficits are associated with changes in the response properties of cortical neurons, we recorded neural activity in the primary auditory cortex (A1) of anesthetized ferrets in which cholinergic inputs had been reduced by making bilateral injections of the immunotoxin ME20.4-SAP in the nucleus basalis (NB) prior to training the animals. The pattern of spontaneous activity of A1 units recorded in the ferrets with cholinergic lesions (NB ACh-) was similar to that in controls, although the proportion of burst-type units was significantly lower. Depletion of ACh also resulted in more synchronous activity in A1. No changes in thresholds, frequency tuning or in the distribution of characteristic frequencies were found in these animals. When tested with normal acoustic inputs, the spatial sensitivity of A1 neurons in the NB ACh- ferrets and the distribution of their preferred interaural level differences also closely resembled those found in control animals, indicating that these properties had not been altered by sound localization training with one ear occluded. Simulating the animals' previous experience with a virtual earplug in one ear reduced the contralateral preference of A1 units in both groups, but caused azimuth sensitivity to change in slightly different ways, which may reflect the modest adaptation observed in the NB ACh- group. These results show that while ACh is required for behavioral adaptation to altered spatial cues, it is not required for maintenance of the spectral and spatial response properties of A1 neurons.

Priming central sound processing circuits through induction of spontaneous activity in the cochlea before hearing onset.

Sensory systems experience a period of intrinsically generated neural activity before maturation is complete and sensory transduction occurs. Here we review evidence describing the mechanisms and functions of this 'spontaneous' activity in the auditory system. Both ex vivo and in vivo studies indicate that this correlated activity is initiated by non-sensory supporting cells within the developing cochlea, which induce depolarization and burst firing of groups of nearby hair cells in the sensory epithelium, activity that is conveyed to auditory neurons that will later process similar sound features. This stereotyped neural burst firing promotes cellular maturation, synaptic refinement, acoustic sensitivity, and establishment of sound-responsive domains in the brain. While sensitive to perturbation, the developing auditory system exhibits remarkable homeostatic mechanisms to preserve periodic burst firing in deaf mice. Preservation of this early spontaneous activity in the context of deafness may enhance the efficacy of later interventions to restore hearing.

Spatiotemporal brain hierarchies of auditory memory recognition and predictive coding.

Our brain is constantly extracting, predicting, and recognising key spatiotemporal features of the physical world in order to survive. While neural processing of visuospatial patterns has been extensively studied, the hierarchical brain mechanisms underlying conscious recognition of auditory sequences and the associated prediction errors remain elusive. Using magnetoencephalography (MEG), we describe the brain functioning of 83 participants during recognition of previously memorised musical sequences and systematic variations. The results show feedforward connections originating from auditory cortices, and extending to the hippocampus, anterior cingulate gyrus, and medial cingulate gyrus. Simultaneously, we observe backward connections operating in the opposite direction. Throughout the sequences, the hippocampus and cingulate gyrus maintain the same hierarchical level, except for the final tone, where the cingulate gyrus assumes the top position within the hierarchy. The evoked responses of memorised sequences and variations engage the same hierarchical brain network but systematically differ in terms of temporal dynamics, strength, and polarity. Furthermore, induced-response analysis shows that alpha and beta power is stronger for the variations, while gamma power is enhanced for the memorised sequences. This study expands on the predictive coding theory by providing quantitative evidence of hierarchical brain mechanisms during conscious memory and predictive processing of auditory sequences.

Cortical dysmorphology and reduced cortico-collicular projections in an animal model of autism spectrum disorder.

Autism spectrum disorder is a neurodevelopmental disability that includes sensory disturbances. Hearing is frequently affected and ranges from deafness to hypersensitivity. In utero exposure to the antiepileptic valproic acid is associated with increased risk of autism spectrum disorder in humans and timed valproic acid exposure is a biologically relevant and validated animal model of autism spectrum disorder. Valproic acid-exposed rats have fewer neurons in their auditory brainstem and thalamus, fewer calbindin-positive neurons, reduced ascending projections to the midbrain and thalamus, elevated thresholds, and delayed auditory brainstem responses. Additionally, in the auditory cortex, valproic acid exposure results in abnormal responses, decreased phase-locking, elevated thresholds, and abnormal tonotopic maps. We therefore hypothesized that in utero, valproic acid exposure would result in fewer neurons in auditory cortex, neuronal dysmorphology, fewer calbindin-positive neurons, and reduced connectivity. We approached this hypothesis using morphometric analyses, immunohistochemistry, and retrograde tract tracing. We found thinner cortical layers but no changes in the density of neurons, smaller pyramidal and non-pyramidal neurons in several regions, fewer neurons immunoreactive for calbindin-positive, and fewer cortical neurons projecting to the inferior colliculus. These results support the widespread impact of the auditory system in autism spectrum disorder and valproic acid-exposed animals and emphasize the utility of simple, noninvasive auditory screening for autism spectrum disorder.

Aging effects on the neural representation and perception of consonant transition cues.

Older listeners have difficulty processing temporal cues that are important for word discrimination, and deficient processing may limit their ability to benefit from these cues. Here, we investigated aging effects on perception and neural representation of the consonant transition and the factors that contribute to successful perception. To further understand the neural mechanisms underlying the changes in processing from brainstem to cortex, we also examined the factors that contribute to exaggerated amplitudes in cortex. We enrolled 30 younger normal-hearing and 30 older normal-hearing participants who met the criteria of clinically normal hearing. Perceptual identification functions were obtained for the words BEAT and WHEAT on a 7-step continuum of consonant-transition duration. Auditory brainstem responses (ABRs) were recorded to click stimuli and frequency-following responses (FFRs) and cortical auditory-evoked potentials were recorded to the endpoints of the BEAT-WHEAT continuum. Perceptual performance for identification of BEAT vs. WHEAT did not differ between younger and older listeners. However, both subcortical and cortical measures of neural representation showed age group differences, such that FFR phase locking was lower but cortical amplitudes (P1 and N1) were higher in older compared to younger listeners. ABR Wave I amplitude and FFR phase locking, but not audiometric thresholds, predicted early cortical amplitudes. Phase locking to the transition region and early cortical peak amplitudes (P1) predicted performance on the perceptual identification function. Overall, results suggest that the neural representation of transition durations and cortical overcompensation may contribute to the ability to perceive transition duration contrasts. Cortical overcompensation appears to be a maladaptive response to decreased neural firing/synchrony.

Alpha9alpha10 knockout mice show altered physiological and behavioral responses to signals in masking noise.

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.

Medial superior olive in the rat: Anatomy, sources of input and axonal projections.

Although rats and mice are among the preferred animal models for investigating many characteristics of auditory function, they are rarely used to study an essential aspect of binaural hearing: the ability of animals to localize the sources of low-frequency sounds by detecting the interaural time difference (ITD), that is the difference in the time at which the sound arrives at each ear. In mammals, ITDs are mostly encoded in the medial superior olive (MSO), one of the main nuclei of the superior olivary complex (SOC). Because of their small heads and high frequency hearing range, rats and mice are often considered unable to use ITDs for sound localization. Moreover, their MSO is frequently viewed as too small or insignificant compared to that of mammals that use ITDs to localize sounds, including cats and gerbils. However, recent research has demonstrated remarkable similarities between most morphological and physiological features of mouse MSO neurons and those of MSO neurons of mammals that use ITDs. In this context, we have analyzed the structure and neural afferent and efferent connections of the rat MSO, which had never been studied by injecting neuroanatomical tracers into the nucleus. The rat MSO spans the SOC longitudinally. It is relatively small caudally, but grows rostrally into a well-developed column of stacked bipolar neurons. By placing small, precise injections of the bidirectional tracer biotinylated dextran amine (BDA) into the MSO, we show that this nucleus is innervated mainly by the most ventral and rostral spherical bushy cells of the anteroventral cochlear nucleus of both sides, and by the most ventrolateral principal neurons of the ipsilateral medial nucleus of the trapezoid body. The same experiments reveal that the MSO densely innervates the most dorsolateral region of the central nucleus of the inferior colliculus, the central region of the dorsal nucleus of the lateral lemniscus, and the most lateral region of the intermediate nucleus of the lateral lemniscus of its own side. Therefore, the MSO is selectively innervated by, and sends projections to, neurons that process low-frequency sounds. The structural and hodological features of the rat MSO are notably similar to those of the MSO of cats and gerbils. While these similarities raise the question of what functions other than ITD coding the MSO performs, they also suggest that the rat MSO is an appropriate model for future MSO-centered research.