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Effects of Non-traumatic Noise and Conductive Hearing Loss on Auditory System Function
Abstract
The effects of traumatic noise-exposure and deafening on auditory system function have received a great deal of attention. However, lower levels of noise as well as temporary conductive hearing loss also have consequences on auditory physiology and hearing. Here we review how abnormal acoustic experience at early ages affects the ascending and descending auditory pathways, as well as hearing behavior.
... Recent work by the Lauer Lab has shown that older mice do not recover behavioral hearing sensitivity after loud noise exposure as well as middle-aged mice. 2 The mechanisms underlying this difference in susceptibility are unclear, but likely involve increased degeneration in the brain or impaired central compensation. 3,4,5 In this project, I will train and determine a reliable machine learning algorithm to quantify cellular size and density the mouse cochlear nucleus and test the hypothesis that the cochlear nucleus, the first stage of the central auditory pathway, shows greater neuronal degeneration after noise exposure in aged compared to young mice. ...
Awardee of Johns Hopkins University Provost’s Undergraduate Research Award
Proposal to compare various cell classification machine learning algorithms and traditional analysis platforms for accuracy and efficiency in quantifying neurons in the mouse cochlear nucleus. To apply the selected platform to quantitatively analyze neuronal degeneration in the cochlear nucleus of young control mice compared to aged mice and mice exposed to loud noise at various ages.
... Depending on the location of the damage in the auditory system, deafness is divided into conductive and sensorineural types (Seddon et al., 2012). Conductive deafness occurs due to lesions in the tympanic membrane and the auditory tuberosity, which impede sound transmission to the inner ear (Lauer et al., 2019). On the other hand, sensorineural deafness is mainly the result of lesions in the auditory center, including the inner ear and the auditory nerve. ...
Hearing impairment is a global health problem. Stem cell therapy has become a cutting-edge approach to tissue regeneration. In this review, the recent advances in stem cell therapy for hearing loss have been discussed. Nanomaterials can modulate the stem cell microenvironment to augment the therapeutic effects further. The potential of combining nanomaterials with stem cells for repairing and regenerating damaged inner ear hair cells (HCs) and spiral ganglion neurons (SGNs) has also been discussed. Stem cell-derived exosomes can contribute to the repair and regeneration of damaged tissue, and the research progress on exosome-based hearing loss treatment has been summarized as well. Despite stem cell therapy’s technical and practical limitations, the findings reported so far are promising and warrant further investigation for eventual clinical translation.
... Hearing loss may occur for various reasons and has a variety of consequences in everyday life. Prenatal etiologist may cause hearing loss, inner ear malformations, congenital infections, aging, ear infection, genetics, head injuries, chemotherapy agents, ototoxic medication or antibiotics, as well as excessive noise exposure (Rusinek, 2021; Aline et al., 2020; Borges et al., 2020;Vohr, 2018;Lauer et al., 2019). Hearing loss has several consequences, including difficulties with language, education, and psychological functioning, cognitive decline, www.iarjournals.com ...
Hearing loss is the inability to hear sounds, in part or whole, and may affect one or both ears. It caused difficulties with language, education, and psychological functioning, cognitive decline, binaural hearing and speech perception in noise, depression, behavioral changes, and decreased functional status. The range of hearing level is normal (-10 to 20 dB), mild (20 to 34 dB), moderate (35 to 49 dB), moderately severe (50 to 64 dB), powerful (65 to 79 dB), and severe to profound. There are three types of hearing impairment, including conductive, sensorineural, and mixed hearing loss. Conductive hearing loss happens when a problem with the outer or middle ear stops sound from reaching the inner ear. Sensorineural hearing loss is caused by injury to the inner ear or the nerve path leading to the inner ear. Mixed hearing loss indicates that the outer or middle ear, the inner ear, and the auditory nerve have been damaged. The most common cause of noise-induced hearing loss (NIHL) and a severe threat to public health is the rising levels of ambient noise from working and the surrounding environment. Audiometry tests allow for the diagnosis of hearing loss, the measurement of the degree to which hearing loss has occurred, and the monitoring of changes in a person's hearing throughout their lifetime. Audiometry tests allow for the diagnosis of hearing loss, the measurement of the degree to which hearing loss has occurred, and the monitoring of hearing changes throughout their lifetime.
... However, unlike our model of noise-induced cochlear damage, cochlear denervation was induced with bilateral cochlear application of ouabain, which eliminates~95% of the type 1 SGNs. Since the type and the severity of peripheral organ damage may result in heterogeneous cortical plasticity 7,10,16,21,30,[93][94][95][96][97][98][99] , noise-and ouabain-induced damage to the cochlea may trigger different trajectories of plasticity in A1 neuronal subtypes. Another explanation for the observed differences could arise from differences in the experimental design, such as the sound-stimuli used (broadband vs. 12 kHz pure tones 11 ) and the number of PVs tracked (82 vs. 29 11 ). ...
Peripheral sensory organ damage leads to compensatory cortical plasticity that is associated with a remarkable recovery of cortical responses to sound. The precise mechanisms that explain how this plasticity is implemented and distributed over a diverse collection of excitatory and inhibitory cortical neurons remain unknown. After noise trauma and persistent peripheral deficits, we found recovered sound-evoked activity in mouse A1 excitatory principal neurons (PNs), parvalbumin- and vasoactive intestinal peptide-expressing neurons (PVs and VIPs), but reduced activity in somatostatin-expressing neurons (SOMs). This cell-type-specific recovery was also associated with cell-type-specific intrinsic plasticity. These findings, along with our computational modelling results, are consistent with the notion that PV plasticity contributes to PN stability, SOM plasticity allows for increased PN and PV activity, and VIP plasticity enables PN and PV recovery by inhibiting SOMs.
... Однако обычно в контексте исследований рассматривается травматический шум, то есть нарушающий предельно допустимые величины, как шум на производстве или в ходе военных действий. Тем не менее, возможность воздействия нетравматического, но постоянного шума на органы слуха также изучается и уже доказана на моделях животных [90]. ...
Introduction. Environment and its indicators as health risk factors have been widely studied for a long time. The atmospheric air and factors polluting it are confirmed as the most important environmental factors that influence human’s health. Nevertheless, people spend up to 90% of their time indoors. Indicators of indoor environment have another origins and they can also have another scales. At the same time, these factors can be influenced easily, thus decreasing their negative impact on health. The aim of our review is to study information about impact of physical factors of indoor environment on human organism and methods of maintaining them within safe level. For analysis we chose several factors depending on their prevalence, opportunities to measure their levels and availability of the methods to correct them. Materials and methods. The search was conducted using PubMed, Google Scholar and Elibrary data bases. Fundamental literature, such as legislative act, were used. Results. Nowadays, disease prevention via elimination of risk factors influence on human health is gaining more and more attention. There are various devices that capture air indicators in houses and public buildings. Their use helps to maintain parameters within comfort level. We summarized information about the most important and wide-spread factors, their impact on health, methods for their measurement and solutions for their correction. Nevertheless, there are not enough devices which enable to monitor several important factors simultaneously. That problem leads to using different devices and each of them need calibration and technical service. Conclusion. Nowadays the impact of environmental factors on human health is widely studied and new information about this problem appears constantly. Dynamic monitoring of indicators of environmental factors is necessary for decreasing negative influence on health. An important step towards simultaneous monitoring of the most significant indoor factors is developing of technical solutions which can remove the duty to service many devices separately. These technical solutions can also propose methods for maintaining these factors within safe levels.
... Unilateral hearing loss has profound effects on binaural circuits (Moore et al., 1999;Moore and King, 2004;Sanes and Bao, 2009;Popescu and Polley, 2010;Persic et al., 2020). Recent reviews have outlined the effects of hearing loss on auditory brainstem plasticity (Sanes and Bao, 2009;Tzounopoulos and Kraus, 2009;Anderson et al., 2010;Keating and King, 2013;Friauf et al., 2015;Lauer et al., 2019;Persic et al., 2020;Rubio, 2020), and upon localization behavior in rats ( (Clements and Kelly, 1978), ferrets (Moore et al., 1999;Keating and King, 2013;Kumpik and King, 2019), gerbils (Maier et al., 2008) and barn owls (Knudsen, 2002;Bergan and Knudsen, 2007;Keuroghlian and Knudsen, 2007). Previous studies have shown clear refinement of inputs to the ITD sensitive neurons of the mammalian medial superior olive (Kapfer et al., 2002;Chang et al., 2003;Magnusson et al., 2005;Werthat et al., 2008;Winters and Golding, 2018). ...
Barn owls experience increasing interaural time differences (ITDs) during development, because their head width more than doubles in the month after hatching. We therefore hypothesized that their ITD detection circuit might be modified by experience. To test this, we raised owls with unilateral ear inserts that delayed and attenuated the acoustic signal, then measured the ITD representation in the brainstem nucleus laminaris (NL) when they were adult. The ITD circuit is composed of delay line inputs to coincidence detectors, and we predicted that plastic changes would lead to shorter delays in the axons from the manipulated ear, and complementary shifts in ITD representation on the two sides. In owls that received ear inserts starting around P14, the maps of ITD shifted in the predicted direction, but only on the ipsilateral side, and only in those tonotopic regions that had not experienced auditory stimulation prior to insertion. The contralateral map did not change. Experience-dependent plasticity of the ITD circuit occurs in NL, and our data suggest that ipsilateral and contralateral delays are independently regulated. Thus, altered auditory input during development leads to long-lasting changes in the representation of ITD.
Significance Statement
The early life of barn owls is marked by increasing sensitivity to sound, and by increasing ITDs. Their prolonged post-hatch development allowed us to examine the role of altered auditory experience on the development of ITD detection circuits. We raised owls with a unilateral ear insert and found that their maps of ITD were altered by experience, but only in those tonotopic regions that had not experienced auditory stimulation prior to insertion. Thus experience-induced plasticity allows the sound localization circuits to be customized to individual characteristics, such as the size of the head, and potentially to compensate for natural conductive hearing losses.
... Furthermore, aging, with its slowed or limited recovery from tissue damage, contributes to the high occurrence of auditory impairments in older people (Collins, 1997). In this sense, age-related hearing loss (ARHL, also known as presbycusis) is a disability with high prevalence (Gates and Mills, 2005;Fu et al., 2010;Lauer et al., 2019) and one of the most important factors leading to cognitive decline and dementia (Deal et al., 2018;Loughrey et al., 2018;Livingston et al., 2020). It is widely accepted that pathological alterations in the peripheral auditory organ and the consequent changes in central plasticity are the mechanisms underlying the ARHL (Frisina and Walton, 2006;Caspary et al., 2008;Hughes et al., 2010;Parthasarathy and Kujawa, 2018;Wang M. et al., 2021). ...
The medial nucleus of the trapezoid body (MNTB) is an integral component of the auditory brainstem circuitry involved in sound localization. The giant presynaptic nerve terminal with multiple active zones, the calyx of Held (CH), is a hallmark of this nucleus, which mediates fast and synchronized glutamatergic synaptic transmission. To delineate how these synaptic structures adapt to reduced auditory afferents due to aging, we acquired and reconstructed circuitry-level volumes of mouse MNTB at different ages (3 weeks, 6, 18, and 24 months) using serial block-face electron microscopy. We used C57BL/6J, the most widely inbred mouse strain used for transgenic lines, which displays a type of age-related hearing loss. We found that MNTB neurons reduce in density with age. Surprisingly we observed an average of approximately 10% of poly-innervated MNTB neurons along the mouse lifespan, with prevalence in the low frequency region. Moreover, a tonotopy-dependent heterogeneity in CH morphology was observed in young but not in older mice. In conclusion, our data support the notion that age-related hearing impairments can be in part a direct consequence of several structural alterations and circuit remodeling in the brainstem.
... Furthermore, the long-term stability of hearing loss is rarely assessed behaviorally in animal models, but models of early-onset and lateonset age-related hearing loss suggest differential effects on the stability of hearing in quiet and noise over time (Prosen et al., 2003;. The long-term effects of aging and noise interactions on auditory function have not been thoroughly studied in mammalian models (for review, see Lauer et al., 2019). ...
Aging leads to degeneration of the peripheral and central auditory systems, hearing loss, and difficulty understanding sounds in noise. Aging is also associated with changes in susceptibility to or recovery from damaging noise exposures, although the effects of the interaction between acute noise exposure and age on the perception of sounds are not well studied. We tested these effects in the CBA/CaJ mouse model of age-related hearing loss using operant conditioning procedures before and after noise exposure and longitudinally measured changes in their sensitivity for detecting tones in quiet or noise backgrounds. Cochleae from a subset of the behaviorally tested mice were immunolabeled to examine organ of Corti damage relative to what is expected based on aging alone. Mice tested in both quiet and noise background conditions experienced worse behavioral sensitivity immediately after noise exposure, but mice exposed at older ages generally showed greater threshold shifts and reduced recovery over time. Surprisingly, day-to-day stability in thresholds was markedly higher for mice detecting signals in the presence of a noise masker compared with detection in quiet conditions. Cochlear analysis revealed decreases in the total number of outer hair cells (OHCs) and the number of ribbons per inner cell in high-frequency regions in aged, noise-exposed mice relative to aging alone. Our findings build on previous work showing interactions between age and noise exposure and add that background noise can increase the stability of behavioral hearing sensitivity after noise damage.
... The role between sensorineural hearing loss, central auditory disorders such as tinnitus and hyperacusis, and OC function is complex to sort out because of the interplay between these conditions. Cochlear damage can lead to changes in the central auditory system, such as the loss of inhibition and central gain compensation purported to underlie tinnitus, hyperacusis, and loudness recruitment ( Auerbach et al., 2019 ;Lauer et al., 2019 ;Sheppard et al., 2020 ). This in turn could lead to abnormal OC activation. ...
The role of the mammalian auditory olivocochlear efferent system in hearing has long been the subject of debate. Its ability to protect against damaging noise exposure is clear, but whether or not this is the primary function of a system that evolved in the absence of industrial noise remains controversial. Here we review the behavioral consequences of olivocochlear activation and diminished olivocochlear function. Attempts to demonstrate a role for hearing in noise have yielded conflicting results in both animal and human studies. A role in selective attention to sounds in the presence of distractors, or attention to visual stimuli in the presence of competing auditory stimuli, has been established in animal models, but again behavioral studies in humans remain equivocal. Auditory processing deficits occur in models of congenital olivocochlear dysfunction, but these deficits likely reflect abnormal central auditory development rather than direct effects of olivocochlear feedback. Additional proposed roles in age-related hearing loss, tinnitus, hyperacusis, and binaural or spatial hearing, are intriguing, but require additional study. These behavioral studies almost exclusively focus on medial olivocochlear effects, and many relied on lesioning techniques that can have unspecific effects. The consequences of lateral olivocochlear and of corticofugal pathway activation for perception remain unknown. As new tools for targeted manipulation of olivocochlear neurons emerge, there is potential for a transformation of our understanding of the role of the olivocochlear system in behavior across species.
... Recently, studies of asymmetrical hearing loss have shown that earlier hearing deprivation can lead to further weakening of auditory cortex development and of the auditory pathways in the impaired ear, contributing to abnormal binaural integration and temporal processing [10,[26][27][28]. A number of studies have supported that early hearing intervention may have provided better results [26,29,30] ,as the auditory system is obvious plastic in animals and humans [31,32]. Moreover, a recent study suggested that different auditory processes develop at different rates, relying on the age [33]. ...
Objective
This study assessed the safety and sound-localisation ability of the Vibrant Soundbridge (VSB) (Med-EL, Innsbruck, Austria) in patients with unilateral microtia and atresia (MA).Methods
This was a single-centre retrospective research study. Twelve subjects with unilateral conductive hearing loss (UCHL) caused by ipsilateral MA were recruited, each of whom underwent VSB implantation and auricular reconstruction. The bone-conduction (BC) threshold was measured postoperatively, and the accuracy of sound localisation was evaluated at least 6 months after surgery. Horizontal sound-localisation performance was investigated with the VSB activated and inactivated, at varying sound stimuli levels (65, 70 and 75 dB SPL). Localisation benefit was analysed via the mean absolute error (MAE).ResultsThere was no statistical difference in mean BC threshold of impaired ears measured preoperatively and postoperatively. When compared with VSB-inactivated condition, the MAE increased significantly in unilateral MA patients in the VSB-activated condition. Besides, sound-localisation performance worsened remarkably when sound was presented at 70 dB SPL and 75 dB SPL. Regarding the side of signal location, the average MAE with the VSB device was much higher than that without the VSB when sound was from the normal-hearing ear. However, no significant difference was observed when sound was located from the impaired ear.Conclusion
This study demonstrates that in patients with unilateral MA, the VSB device does not affect inner-ear function. Sound-localisation ability is not improved, but deteriorated at follow-up. Our results suggest that the VSB-aided localisation abilities may be related to the thresholds between the ears, plasticity of auditory system and duration of use of VSB.
... This result might indicate that decreases in the sound levels, without primary neural damage, could cause neural changes [10]. Moreover, there are numerous studies that reported activity-dependent changes in the central auditory system at different levels (synaptic, cellular, and system levels) and across different disciplines [11][12][13]. However, the changes in VGLUT expression after decreasing the sound levels are less well known, and studying this alteration could provide valuable insights into the magnitude and spatial distribution of auditory and non-auditory innervation of the CN. ...
Auditory nerve fibers synapse onto the cochlear nucleus (CN) and are labeled using the vesicular glutamate transporter-1 (VGLUT-1), whereas non-auditory inputs are labeled using the VGLUT-2. However, the underlying regulatory mechanism of VGLUT expression in the CN remains unknown. We examined whether a sound level decrease, without primary neural damage, induces cellular and VGLUT expression change in the CN, and examined the potential for neural plasticity of the CN using unilateral conductive hearing loss models. We inserted earplugs in 8-week-old mice unilaterally for 4 weeks and subsequently removed them for another 4 weeks. Although the threshold of an auditory brainstem response significantly increased across all tested frequencies following earplug insertion, it completely recovered after earplug removal. Auditory deprivation had no significant impact on spiral ganglion and ventral CN (VCN) neurons’ survival. Conversely, although the cell size and VGLUT-1 expression in the VCN significantly decreased after earplug insertion, VGLUT-2 expression in the granule cell lamina significantly increased. These cell sizes decreased and the alterations in VGLUT-1 and -2 expression almost completely recovered at 1 month after earplug removal. Our results suggested that the cell size and VGLUT expression in the CN have a neuroplasticity capacity, which is regulated by increases and decreases in sound levels. Restoration of the sound levels might partly prevent cell size decrease and maintain VGLUT expression in the CN.
... Several studies have shown that CHL can affect auditory brainstem response (ABR) waves and, subsequently, cochlear nucleus activity. In addition, it can upregulate the glutamate receptor subunits (Lauer et al. 2019). Moreover, CHL alters structural and molecular synaptic components in the auditory periphery and center during the early developmental stages (Aizawa and Eggermont 2007;Clarkson et al. 2016;Qi et al. 2019). ...
We examined the functional and structural changes of auditory neurons (ANs) in adult mice after conductive hearing loss (CHL). Earplugs (EPs) were bilaterally inserted in male 8-week-old mice for 4 weeks [EP(+) group] and subsequently removed for 4 weeks [EP(+/−) group]. We examined the control mice [EP(−) group] with no EPs inserted at 12 weeks. The auditory brainstem response (ABR) was measured to determine the cochlear function before and after EP insertion, after EP removal, and at 4 weeks following EP removal. We examined the cochleae for hair cell (HC) and spiral ganglion neuron survival, synaptic and neural properties, and AN myelination. There was a significant elevation of the ABR threshold across all tested frequencies after EP insertion. After removing the occlusion, these threshold shifts were fully recovered. Compared with the EP(−) mice, the EP(+) mice showed a significant decrease in the ABR peak 1 amplitude and a significantly prolonged latency at all tested frequencies. There was no significant effect of auditory deprivation on the survival of HCs and ANs. Conversely, auditory deprivation caused significant damage to the synapses and myelin and a significant decrease in the AN size. Although functional changes in the ABR amplitude and latency did not fully recover in the EP(+/−) mice, almost all anatomical changes were fully recovered in the EP(+/−) mice; however, cochlear synapses only showed partial recovery. These results suggest that auditory activities are required to maintain peripheral auditory synapses and myelination in adults. The auditory deprivation model allows for assessment of the mechanisms of synaptopathy and demyelination in the auditory periphery, and synaptic and myelin regeneration in sensorineural hearing loss.
... The increasingly utilized gap prepulse inhibition of the acoustic startle (GPIAS) technique (Berger et al., 2013;Turner et al., 2006), although providing reproducible results and valuable insights into tinnitus pathophysiology in animal models, can be affected by hearing loss and therefore can only reliably be used if there is no measurable hearing loss in animals subjects. Even hidden hearing loss could affect the perception of a silent gap in a background noise (Lauer et al., 2019). Therefore, this review has confined itself to studies in which hearing thresholds have returned to normal by the time of tinnitus assessment and in which thresholds or suprathreshold hearing are equivalent in animals defined as having or not having tinnitus. ...
Tinnitus, sound perception in the absence of physical stimuli, occurs in 15% of the population and is the top-reported disability for soldiers after combat. Noise overexposure is a major factor associated with tinnitus but does not always lead to tinnitus. Furthermore, people with normal audiograms can get tinnitus. In animal models, equivalent cochlear damage occurs in animals with and without behavioral evidence of tinnitus. But cochlear-nerve-recipient neurons in the brainstem demonstrate distinct, synchronized spontaneous firing patterns only in animals that develop tinnitus, driving activity in central brain regions and ultimately giving rise to phantom perception. Examining tinnitus-specific changes in single-cell populations enables us to begin to distinguish neural changes due to tinnitus from those that are due to hearing loss.
Background
Chronic unilateral hearing loss causes imbalanced auditory input to the brain that triggers cortical reorganization. The effect of sensorineural hearing loss on the central auditory system (CAS) has been thoroughly studied, while there is a paucity of research on the effect of conductive hearing loss (CHL). The aim of this study was to assess the P1-N1-P2 cortical auditory evoked response potential (CAEP) in adult individuals with chronic acquired unilateral CHL.
Methods
This study included 108 participants of both genders: 54 patients with unilateral chronic CHL who were compared to well-matched 54 controls. All were subjected to history-taking, otologic examination, basic audiological evaluation, and bone conduction N1-P2 CAEP.
Results
The affected ears of the cases showed highly statistically significant shorter CAEPs N1, P2, N1-P2 latencies but not P1, and showed highly statistically significant larger N1, P2, N1P2, amplitude than the control group. Latencies decreased and amplitudes increased as the degree of CHL increased, but were not affected by patients’ age, side, or duration of the CHL. Cases with tinnitus had statistically significant and worse results than those without tinnitus.
Conclusion
Unilateral chronic CHL might enhance neurocortical plasticity, with greater changes occurring at greater degrees of the CHL.
Hearing loss is the symptom most commonly seen in association with tinnitus. According to the various models of tinnitus development, hearing loss also represents the crucial trigger mechanism for the development of tinnitus. Since different structures such as the outer ear, the middle ear and the inner ear are involved in the peripheral hearing process, a distinction is also made between conductive hearing loss, sensorineural hearing loss and retrocochlear hearing loss, depending on the localization of the pathology. This chapter highlights the main causes of conductive hearing loss and sensorineural hearing loss. A detailed clarification of the causes of hearing loss in tinnitus is important, as in many cases this also leads to specific therapies, which ideally will result in an improvement of hearing loss and tinnitus symptoms. In the case of middle ear hearing loss, these therapeutic approaches are primarily surgical in nature (tympanoplasty, stapes surgery), in the case of sensorineural hearing loss, the improvement is generally based on a prosthetic fitting with hearing aids or cochlear implants.
Interaural time differences (ITDs) are a major cue for sound localization and change with increasing head size. Since the barn owl's head width more than doubles in the month after hatching, we hypothesized that development of their ITD detection circuit might be modified by experience. To test this, we raised owls with unilateral ear inserts that delayed and attenuated the acoustic signal, then measured the ITD representation in the brainstem nucleus laminaris (NL) when they were adults. The ITD circuit is composed of delay line inputs to coincidence detectors, and we predicted that plastic changes would lead to shorter delays in the axons from the manipulated ear, and complementary shifts in ITD representation on the two sides. In owls that received ear inserts starting around P14, the maps of ITD shifted in the predicted direction, but only on the ipsilateral side, and only in those tonotopic regions that had not experienced auditory stimulation prior to insertion. The contralateral map did not change. Thus, experience-dependent plasticity of the ITD circuit occurs in NL, and our data suggest that ipsilateral and contralateral delays are independently regulated. As a result, altered auditory input during development leads to long-lasting changes in the representation of ITD.
Significance Statement The early life of barn owls is marked by increasing sensitivity to sound, and by increasing ITDs. Their prolonged post-hatch development allowed us to examine the role of altered auditory experience in the development of ITD detection circuits. We raised owls with a unilateral ear insert and found that their maps of ITD were altered by experience, but only in those tonotopic regions ipsilateral to the occluded ear that had not experienced auditory stimulation prior to insertion. This experience-induced plasticity allows the sound localization circuits to be customized to individual characteristics, such as the size of the head, and potentially to compensate for imbalanced hearing sensitivities between left and right ears.
Synopsis
According to the World Health Organization, ∼15 million children are born prematurely each year. Many of these infants end up spending days to weeks in a neonatal intensive care unit (NICU). Infants who are born prematurely are often exposed to noise and light levels that affect their auditory and visual development. Children often have long-term impairments in cognition, visuospatial processing, hearing, and language. We have developed a rodent model of NICU exposure to light and sound using the Mongolian gerbil (Meriones unguiculatus), which has a low-frequency human-like audiogram and is altricial. To simulate preterm infancy, the eyes and ears were opened prematurely, and animals were exposed to the NICU-like sensory environment throughout the gerbil’s cortical critical period of auditory development. After the animals matured into adults, auditory perceptual testing was carried out followed by auditory brainstem response recordings and then histology to assess the white matter morphology of various brain regions. Compared to normal hearing control animals, NICU sensory-exposed animals had significant impairments in learning at later stages of training, increased auditory thresholds reflecting hearing loss, and smaller cerebellar white matter volumes. These have all been reported in longitudinal studies of preterm infants. These preliminary results suggest that this animal model could provide researchers with an ethical way to explore the effects of the sensory environment in the NICU on the preterm infant’s brain development.
Peripheral sensory organ damage leads to compensatory cortical plasticity that supports a remarkable recovery of perceptual capabilities. A major knowledge gap is the lack of precise mechanisms that explain how this plasticity is implemented and distributed over a diverse collection of excitatory and inhibitory cortical neurons. Here, we explored these mechanisms in mouse A1. After peripheral damage, we found recovered sound-evoked activity of excitatory principal neurons (PNs) and parvalbumin (PVs) interneurons (INs), reduced activity in somatostatin-INs (SOMs), and recovered activity in vasoactive intestinal peptide-INs (VIPs). Given the sequentially organized cortical network where VIPs inhibit INs, SOMs inhibit PVs and PNs, and PVs inhibit PNs, our results suggest that PVs contribute to PN stability, SOMs allow for increased PN and PV activity, and VIPs enable the PN and PV recovery by inhibiting SOMs. These results highlight a strategic, cooperative, and cell-type-specific plasticity program that restores cortical sound processing after peripheral damage.
A significant problem can be exposure to noise, which is one of the negative effects of growing industry and production facilities around the world. Many individuals are exposed to high levels of noise at work, which causes problems. One of the most affected systems of exposure to noise is the auditory system. Hearing is damaged from exposure, such that individuals lose their sense of hearing. In the last 10 years, research has been done globally to prevent and treat noise-related hearing loss. When the data are examined, it can be seen there is protection and treatment for noise-induced hearing losses. The physiopathological effects of noise and new approaches are currently being examined.
Otitis externa (OE) is a condition that involves inflammation of the external ear canal. OE is a commonly reported condition in humans and some veterinary species (for example, dogs, cats), but has not been reported in the literature in macaques. Here, we present a case series of acute and chronic OE likely precipitated by abrasion of the ear canal with a tympanic membrane electrode in 7 adult male rhesus macaques (Macaca mulatta). All animals displayed purulent, mucinous discharge from 1 or both ears with 3 macaques also displaying signs of an upper respiratory tract (URT) infection during the same period. A variety of diagnostic and treatment options were pursued including consultation with an otolaryngologist necessitated by the differences in response to treatment in macaques as compared with other common veterinary species. Due to the nature of the studies in which these macaques were enrolled, standard audiological testing was performed before and after OE, including tympanometry, auditory brainstem responses (ABRs), and distortion product otoacoustic emissions (DPOAEs). After completion of study procedures, relevant tissues were collected for necropsy and histopathology. Impaired hearing was found in all macaques even after apparent resolution of OE signs. Necropsy findings included abnormalities in the tympanic membrane, ossicular chain, and middle ear cavity, suggesting that the hearing impairment was at least partly conductive in nature. We concluded that OE likely resulted from mechanical disruption of the epithelial lining of the ear canal by the ABR electrode, thereby allowing the development of opportunistic infections. OE, while uncommon in macaques, can affect them and should be included as a differential diagnosis of any macaque presenting with otic discharge and/or auricular discomfort.
Cross-modal plasticity occurs when the function of remaining senses is enhanced following deprivation or loss of a sensory modality. Auditory neural responses are enhanced in the auditory cortex, including increased sensitivity and frequency selectivity, following short-term visual deprivation in adult mice (Petrus et al. Neuron 81:664-673, 2014). Whether or not these visual deprivation-induced neural changes translate into improved auditory perception and performance remains unclear. As an initial investigation of the effects of adult visual deprivation on auditory behaviors, CBA/CaJ mice underwent binocular enucleation at 3-4 weeks old and were tested on a battery of learned behavioral tasks, acoustic startle response (ASR), and prepulse inhibition (PPI) tests beginning at least 2 weeks after the enucleation procedure. Auditory brain stem responses (ABRs) were also measured to screen for potential effects of visual deprivation on non-behavioral hearing function. Control and enucleated mice showed similar tone detection sensitivity and frequency discrimination in a conditioned lick suppression test. Both groups showed normal reactivity to sound as measured by ASR in a quiet background. However, when startle-eliciting stimuli were presented in noise, enucleated mice showed decreased ASR amplitude relative to controls. Control and enucleated mice displayed no significant differences in ASR habituation, PPI tests, or ABR thresholds, or wave morphology. Our findings suggest that while adult-onset visual deprivation induces cross-modal plasticity at the synaptic and circuit levels, it does not substantially influence simple auditory behavioral performance.
Approximately 15% of American adults report some degree of difficulty hearing in a noisy environment or have auditory filtering difficulties. There are objective clinical tests of auditory filtering, yet few tests exist for mouse models that do not rely on extensive training. We have used reflex modification audiometry (RMA) and developed exclusion criteria for the mouse model. This RMA based test makes use of the acoustic startle response (ASR) and the ability of prepulses to inhibit the ASR [i.e., prepulse inhibition (PPI)] to assess the mouse's ability to detect prepulse signals presented in quiet or embedded in masking noise. We have studied PPI behavior across four inbred mouse strains with normal cochlear function and developed pre-testing exclusion criteria and test/retest reliability measures. Moreover, because both the medial (MOC) and the lateral (LOC) olivocochlear efferent feedback systems have been proposed to improve auditory behavior performance, especially in noisy backgrounds, we have examined PPI abilities in mice (with their littermate controls) either lacking the MOC receptor subunit α9 nicotinic acetylcholine receptor [α9 nAChR (–/–)] or expressing an overactive receptor [Ld'T mutation in α9 nAChR KI], or lacking an LOC efferent neuropeptide, alpha calcitonin gene-related peptide [αCGRP (–/–)] only in the CNS. Because CGRP receptor formation has been shown to mature from juvenile to adult ages, we also studied if this maturation would be reflected in PPI behavioral responses in juvenile and adult (+/+) controls and in adult αCGRP (–/–) animals. We show that 50% PPI response thresholds (sound level with 50% correct responses) in quiet are decreased in the (–/–) α9 nAChR animals, and 50% PPI responses are increased for mice with an overactive receptor (α9 nAChR KI) and are increased in adult mice lacking αCGRP (–/–). However, in background noise, only mice lacking αCGRP exhibited increased 50% PPI response thresholds, as there were no significant differences between α9 nAChR adult mouse lines and their littermate controls. These findings suggest that MOC and LOC olivocochlear neurotransmission work in tandem to improve behavioral responses to sound. These experiments further pave the way for rapid behavioral hearing assessments in other mouse models.
Piccolo and Bassoon are the two largest cytomatrix of the active zone (CAZ) proteins involved in scaffolding and regulating neurotransmitter release at presynaptic active zones (AZs), but have long been discussed as being functionally redundant. We employed genetic manipulation to bring forth and segregate the role of Piccolo from that of Bassoon at central auditory synapses of the cochlear nucleus—the endbulbs of Held. These synapses specialize in high frequency synaptic transmission, ideally poised to reveal even subtle deficits in the regulation of neurotransmitter release upon molecular perturbation. Combining semi-quantitative immunohistochemistry, electron microscopy, and in vitro and in vivo electrophysiology we first studied signal transmission in Piccolo-deficient mice. Our analysis was not confounded by a cochlear deficit, as a short isoform of Piccolo (“Piccolino”) present at the upstream ribbon synapses of cochlear inner hair cells (IHC), is unaffected by the mutation. Disruption of Piccolo increased the abundance of Bassoon at the AZs of endbulbs, while that of RIM1 was reduced and other CAZ proteins remained unaltered. Presynaptic fiber stimulation revealed smaller amplitude of the evoked excitatory postsynaptic currents (eEPSC), while eEPSC kinetics as well as miniature EPSCs (mEPSCs) remained unchanged. Cumulative analysis of eEPSC trains indicated that the reduced eEPSC amplitude of Piccolo-deficient endbulb synapses is primarily due to a reduced readily releasable pool (RRP) of synaptic vesicles (SV), as was corroborated by a reduction of vesicles at the AZ found on an ultrastructural level. Release probability seemed largely unaltered. Recovery from short-term depression was slowed. We then performed a physiological analysis of endbulb synapses from mice which, in addition to Piccolo deficiency, lacked one functional allele of the Bassoon gene. Analysis of the double-mutant endbulbs revealed an increase in release probability, while the synapses still exhibited the reduced RRP, and the impairment in SV replenishment was exacerbated. We propose additive roles of Piccolo and Bassoon in SV replenishment which in turn influences the organization and size of the RRP, and an additional role of Bassoon in regulation of release probability.
Plasticity of myelination represents a mechanism to tune the flow of information by balancing functional requirements with metabolic and spatial constraints. The auditory system is heavily myelinated and operates at the upper limits of action potential generation frequency and speed observed in the mammalian CNS. This study aimed to characterize the development of myelin within the trapezoid body, a central auditory fiber tract, and determine the influence sensory experience has on this process in mice of both sexes. We find that in vitro conduction speed doubles following hearing onset and the ability to support high frequency firing increase s concurrently. Also in this time, the diameter of trapezoid body axons and the thickness of myelin do
uble, reaching mature-like thickness between 25-35 days of age. Earplugs were used to induce approximately 50dB elevation in auditory thresholds. If introduced at hearing onset, trapezoid body fibers developed thinner axons and myelin than age-matched controls. If plugged during adulthood, the thickest trapezoid body fibers also showed a decrease in myelin. These data demonstrate the need for sensory activity in both development and maintenance of myelin and have important implications in the study of myelin plasticity and how this could relate to sensorineural hearing loss following peripheral impairment.
In childhood, partial hearing loss can produce prolonged deficits in speech perception and temporal processing. However, early therapeutic interventions targeting temporal processing may improve later speech-related outcomes. Gap detection is a measure of auditory temporal resolution that relies on the auditory cortex (ACx), and early auditory deprivation alters intrinsic and synaptic properties in the ACx. Thus, early deprivation should induce deficits in gap detection, which should be reflected in ACx gap sensitivity. We tested whether earplugging-induced, early transient auditory deprivation in male and female Mongolian gerbils caused correlated deficits in behavioral and cortical gap detection, and whether these could be rescued by a novel therapeutic approach: brief exposure to gaps in background noise. Two weeks after earplug removal, animals that had been earplugged from hearing onset throughout auditory critical periods displayed impaired behavioral gap detection thresholds (GDTs), but this deficit was fully reversed by three 1 h sessions of exposure to gaps in noise. In parallel, after earplugging, cortical GDTs increased because fewer cells were sensitive to short gaps, and gap exposure normalized this pattern. Furthermore, in deprived animals, both first-spike latency and first-spike latency jitter increased, while spontaneous and evoked firing rates decreased, suggesting that deprivation causes a wider range of perceptual problems than measured here. These cortical changes all returned to control levels after gap exposure. Thus, brief stimulus exposure, perhaps in a salient context such as the unfamiliar placement into a testing apparatus, rescued impaired gap detection and may have potential as a remediation tool for general auditory processing deficits.
Corticostriatal circuits play a fundamental role in regulating many behaviors, and their dysfunction is associated with many neurological disorders. In contrast, sensory disorders, like hearing loss (HL), are commonly linked with processing deficits at or below the level of the auditory cortex (ACx). However, HL can be accompanied by non-sensory deficits, such as learning delays, suggesting the involvement of regions downstream of ACx. Here, we show that transient developmental HL differentially affected the ACx and its downstream target, the sensory striatum. Following HL, both juvenile ACx layer 5 and striatal neurons displayed an excitatory-inhibitory imbalance and lower firing rates. After hearing was restored, adult ACx neurons recovered balanced excitatory-inhibitory synaptic gain and control-like firing rates, but striatal neuron synapses and firing properties did not recover. Thus, a brief period of abnormal cortical activity may induce cellular impairments that persist into adulthood and contribute to neurological disorders that are striatal in origin.
Auditory activity plays an important role in the development of the auditory system. Decreased activity can result from conductive hearing loss (CHL) associated with otitis media, which may lead to long-term perceptual deficits. The effects of CHL have been mainly studied at later stages of the auditory pathway, but early stages remain less examined. However, changes in early stages could be important because they would affect how information about sounds is conveyed to higher-order areas for further processing and localization. We examined the effects of CHL at auditory nerve synapses onto bushy cells in the mouse anteroventral cochlear nucleus following occlusion of the ear canal. These synapses, called endbulbs of Held, normally show strong depression in voltage-clamp recordings in brain slices. After 1 week of CHL, endbulbs showed even greater depression, reflecting higher release probability. We observed no differences in quantal size between control and occluded mice. We confirmed these observations using mean-variance analysis and the integration method, which also revealed that the number of release sites decreased after occlusion. Consistent with this, synaptic puncta immunopositive for VGLUT1 decreased in area after occlusion. The level of depression and number of release sites both showed recovery after returning to normal conditions. Finally, bushy cells fired fewer action potentials in response to evoked synaptic activity after occlusion, likely because of increased depression and decreased input resistance. These effects appear to reflect a homeostatic, adaptive response of auditory nerve synapses to reduced activity. These effects may have important implications for perceptual changes following CHL.
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Sound deprivation by conductive hearing loss increases hearing thresholds, but little is known about the response of the auditory brainstem during and after conductive hearing loss. Here, we show in young adult rats that 10 d of monaural conductive hearing loss (i.e., earplugging) leads to hearing deficits that persist after sound levels are restored. Hearing thresholds in response to clicks and frequencies higher than 8 kHz remain increased after a 10 d recovery period. Neural output from the cochlear nucleus measured at 10 dB above threshold is reduced and followed by an overcompensation at the level of the lateral lemniscus. We assessed whether structural and molecular substrates at auditory nerve (endbulb of Held) synapses in the cochlear nucleus could explain these long-lasting changes in hearing processing. During earplugging, vGluT1 expression in the presynaptic terminal decreased and synaptic vesicles were smaller. Together, there was an increase in postsynaptic density (PSD) thickness and an upregulation of GluA3 AMPA receptor subunits on bushy cells. After earplug removal and a 10 d recovery period, the density of synaptic vesicles increased, vesicles were also larger, and the PSD of endbulb synapses was larger and thicker. The upregulation of the GluA3 AMPAR subunit observed during earplugging was maintained after the recovery period. This suggests that GluA3 plays a role in plasticity in the cochlear nucleus. Our study demonstrates that sound deprivation has long-lasting alterations on structural and molecular presynaptic and postsynaptic components at the level of the first auditory nerve synapse in the auditory brainstem.
Significance statement:
Despite being the second most prevalent form of hearing loss, conductive hearing loss and its effects on central synapses have received relatively little attention. Here, we show that 10 d of monaural conductive hearing loss leads to an increase in hearing thresholds, to an increased central gain upstream of the cochlear nucleus at the level of the lateral lemniscus, and to long-lasting presynaptic and postsynaptic structural and molecular effects at the endbulb of the Held synapse. Knowledge of the structural and molecular changes associated with decreased sensory experience, along with their potential reversibility, is important for the treatment of hearing deficits, such as hyperacusis and chronic otitis media with effusion, which is prevalent in young children with language acquisition or educational disabilities.
Synapses between cochlear nerve terminals and hair cells are the most vulnerable elements in the inner ear in both noise-induced and age-related hearing loss, and this neuropathy is exacerbated in the absence of efferent feedback from the olivocochlear bundle. If age-related loss is dominated by a lifetime of exposure to environmental sounds, reduction of acoustic drive to the inner ear might improve cochlear preservation throughout life. To test this, we removed the tympanic membrane unilaterally in one group of young adult mice, removed the olivocochlear bundle in another group and compared their cochlear function and innervation to age-matched controls one year later. Results showed that tympanic membrane removal, and the associated threshold elevation, was counterproductive: cochlear efferent innervation was dramatically reduced, especially the lateral olivocochlear terminals to the inner hair cell area, and there was a corresponding reduction in the number of cochlear nerve synapses. This loss led to a decrease in the amplitude of the suprathreshold cochlear neural responses. Similar results were seen in two cases with conductive hearing loss due to chronic otitis media. Outer hair cell death was increased only in ears lacking medial olivocochlear innervation following olivocochlear bundle cuts. Results suggest the novel ideas that 1) the olivocochlear efferent pathway has a dramatic use-dependent plasticity even in the adult ear and 2) a component of the lingering auditory processing disorder seen in humans after persistent middle-ear infections is cochlear in origin.
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It is not known why tinnitus occurs in some cases of hearing damage but not others. Abnormalities of excitation-inhibition balance could influence whether tinnitus develops and its severity if it does. Animal models of hearing damage, which also produce tinnitus based on behavioral evidence, have identified abnormalities of GABAergic inhibition, both cortically and subcortically. However, the precise relationships of GABA inhibitory changes to tinnitus itself, as opposed to other consequences of hearing damage, remain uncertain. Here, we used magnetic resonance spectroscopy to non-invasively quantify GABA in the left (LAC) and right (RAC) auditory cortices of a group of 14 patients with lateralized tinnitus (eight left ear) and 14 controls matched for age, sex, and hearing. We also explored the potential relationships with other brain metabolites (i.e., choline, N-acetylaspartate, and creatine). The presence of tinnitus was associated with a reduction in auditory cortex GABA concentration. Regardless of tinnitus laterality, post hoc testing indicated reductions that were significant in RAC and nonsignificant in LAC. Tinnitus severity and hearing loss were correlated positively with RAC choline but not GABA. We discuss the results in the context of current models of tinnitus and methodological constraints.
Significance statement:
Permanently affecting one in seven adults, tinnitus lacks both widely effective treatments and adequate understanding of its brain mechanisms. Existing animal models represent tinnitus that may not be distinguishable from homeostatic responses to the auditory insults used to induce it. Human studies can be well controlled in this regard but are usually not (with few even matching control subjects for hearing loss) and are limited in scope as a result of relying solely on non-invasive recording techniques. Here, we exploit recent advances in non-invasive spectroscopic techniques to establish, in a human study tightly controlled for hearing loss and hyperacusis, that tinnitus is associated with a significant reduction in auditory cortex GABA concentration, which has implications for understanding and treatment of the condition.
Large intersubject variability in the susceptibility to noise-induced hearing loss (NIHL) is known to occur in both humans and animals. It has been suggested that the olivocochlear system (OCS) plays a significant role in protecting the cochlea from exposure to high levels of noise. A mini literature review about the scientific evidence from animal and human studies about the association between the function of the OCS and susceptibility to NIHL was carried out. Animal data consistently show that de-efferented ears exhibit larger temporary threshold shift (TTS) and permanent threshold shift (PTS) than efferented ears. Data from human studies do not consistently show a correlation between the strength of the OCS function and amount of TTS. Further research on human subjects is required to determine how the OCS function could be used to predict susceptibility to NIHL in individual subjects.
As a consequence of rearing newborn kittens in an abnormal acoustic environment, the cochleotopic representation in primary auditory cortex (AI) develops abnormally. Kittens were exposed to a continuous 8 kHz FM (+I kHz) signal (55-75 dB SPL) during a period from birth to three months of age. At maturity, frequency maps in primary auditory cortex were determined and compared with age-matched controls. We find a significant expansion of the &12 kHz frequency region of the map.
During nervous system development, critical periods are usually defined as early periods during which manipulations dramatically change neuronal structure or function, whereas the same manipulations in mature animals have little or no effect on the same property. Neurons in the ventral cochlear nucleus (CN) are dependent on excitatory afferent input for survival during a critical period of development. Cochlear removal in young mammals and birds results in rapid death of target neurons in the CN. Cochlear removal in older animals results in little or no neuron death. However, the extent to which hair-cell-specific afferent activity prevents neuronal death in the neonatal brain is unknown. We further explore this phenomenon using a new mouse model that allows temporal control of cochlear hair cell deletion. Hair cells express the human diphtheria toxin (DT) receptor behind the Pou4f3 promoter. Injections of DT resulted in nearly complete loss of organ of Corti hair cells within 1 week of injection regardless of the age of injection. Injection of DT did not influence surrounding supporting cells directly in the sensory epithelium or spiral ganglion neurons (SGNs). Loss of hair cells in neonates resulted in rapid and profound neuronal loss in the ventral CN, but not when hair cells were eliminated at a more mature age. In addition, normal survival of SGNs was dependent on hair cell integrity early in development and less so in mature animals. This defines a previously undocumented critical period for SGN survival.
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Hyperpolarization-activated non-specific cation permeable channels (HCN) mediate IH currents which are modulated by cGMP, cAMP and by nitric oxide (NO) signalling. Channel properties depend upon subunit composition (HCN1-4 and accessory subunits) as demonstrated in expression systems, however physiological relevance requires investigation in native neurons with intact intracellular signalling. Here we use the superior olivary complex (SOC), which exhibits a distinctive pattern of HCN1 and HCN2 expression, to investigate NO modulation of the respective IH currents, and compare properties in wild type and HCN1 knockout mice. The medial nucleus of the trapezoid body (MNTB) expresses HCN2 subunits exclusively, and sends inhibitory projections to the medial and lateral superior olives (MSO, LSO) and the superior paraolivary nucleus (SPN). In contrast to the MNTB, these target nuclei possess an IH with fast kinetics, and express HCN1 subunits. NO is generated in the SOC following synaptic activity and here we show that NO selectively suppresses HCN1, while enhancing IH mediated by HCN2 subunits. NO hyperpolarizes the half-activation of HCN1-mediated currents and slows the kinetics of native IH currents in the MSO, LSO and SPN. This modulation was independent of cGMP and absent in transgenic mice lacking HCN1. Independently, NO signalling depolarizes the half-activation of HCN2-mediated IH currents in a cGMP-dependent manner. Thus NO selectively suppresses fast HCN1-mediated IH and facilitates a slow HCN2-mediated IH , so generating a spectrum of modulation, dependent on the local expression of HCN1 and/or HCN2 and the actions of NO signalling. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Data from our laboratory show that the auditory brain is highly malleable by experience. We establish a base of knowledge that describes the normal structure and workings at the initial stages of the central auditory system. This research is expanded to include the associated pathology in the auditory brain stem created by hearing loss. Utilizing the congenitally deaf white cat, we demonstrate the way that cells, synapses, and circuits are pathologically affected by sound deprivation. We further show that the restoration of auditory nerve activity via electrical stimulation through cochlear implants serves to correct key features of brain pathology caused by hearing loss. The data suggest that rigorous training with cochlear implants and/or hearing aids offers the promise of heretofore unattained benefits.
Atypical medial olivo-cochlear (MOC) feedback from brainstem to cochlea has been proposed to play a role in tinnitus, but even well-constructed tests of this idea have yielded inconsistent results. Here, it was hypothesized that low sound tolerance (mild to moderate hyperacusis), which can accompany tinnitus or occur on its own, might contribute to the inconsistency. Sound-level tolerance (SLT) was assessed in subjects (all men) with clinically normal or near-normal thresholds to form threshold-, age-, and sex-matched groups: (1) no tinnitus/high SLT, (2) no tinnitus/low SLT, (3) tinnitus/high SLT, and (4) tinnitus/low SLT. MOC function was measured from the ear canal as the change in magnitude of distortion-product otoacoustic emissions (DPOAE) elicited by broadband noise presented to the contralateral ear. The noise reduced DPOAE magnitude in all groups ("contralateral suppression"), but significantly more reduction occurred in groups with tinnitus and/or low SLT, indicating hyper-responsiveness of the MOC system compared to the group with no tinnitus/high SLT. The results suggest hyper-responsiveness of the interneurons of the MOC system residing in the cochlear nucleus and/or MOC neurons themselves. The present data, combined with previous human and animal data, indicate that neural pathways involving every major division of the cochlear nucleus manifest hyperactivity and/or hyper-responsiveness in tinnitus and/or low SLT. The over-activation may develop in each pathway separately. However, a more parsimonious hypothesis is that top-down neuromodulation is the driving force behind ubiquitous over-activation of the auditory brainstem and may correspond to attentional spotlighting on the auditory domain in tinnitus and hyperacusis.
It has previously been shown that environmental enrichment can enhance structural plasticity in the brain and thereby improve cognitive and behavioral function. In this study, we reared developmentally noise-exposed rats in an acoustic-enriched environment for ∼4 weeks to investigate whether or not enrichment could restore developmentally degraded behavioral and neuronal processing of sound frequency. We found that noise-exposed rats had significantly elevated sound frequency discrimination thresholds compared with age-matched naive rats. Environmental acoustic enrichment nearly restored to normal the behavioral deficit resulting from early disrupted acoustic inputs. Signs of both degraded frequency selectivity of neurons as measured by the bandwidth of frequency tuning curves and decreased long-term potentiation of field potentials recorded in the primary auditory cortex of these noise-exposed rats also were reversed partially. The observed behavioral and physiological effects induced by enrichment were accompanied by recovery of cortical expressions of certain NMDA and GABAA receptor subunits and brain-derived neurotrophic factor. These studies in a rodent model show that environmental acoustic enrichment promotes recovery from early noise-induced auditory cortical dysfunction and indicate a therapeutic potential of this noninvasive approach for normalizing neurological function from pathologies that cause hearing and associated language impairments in older children and adults.
Sensory deprivation can induce profound changes to central processing during developmental critical periods (CPs), and the
recovery of normal function is maximal if the sensory input is restored during these epochs. Therefore, we asked whether mild
and transient hearing loss (HL) during discrete CPs could induce changes to cortical cellular physiology. Electrical and inhibitory
synaptic properties were obtained from auditory cortex pyramidal neurons using whole-cell recordings after bilateral earplug
insertion or following earplug removal. Varying the age of HL onset revealed brief CPs of vulnerability for membrane and firing
properties, as well as, inhibitory synaptic currents. These CPs closed 1 week after ear canal opening on postnatal day (P)
18. To examine whether the cellular properties could recover from HL, earplugs were removed prior to (P17) or after (P23),
the closure of these CPs. The earlier age of hearing restoration led to greater recovery of cellular function, but firing
rate remained disrupted. When earplugs were removed after the closure of these CPs, several changes persisted into adulthood.
Therefore, long-lasting cellular deficits that emerge from transient deprivation during a CP may contribute to delayed acquisition
of auditory skills in children who experience temporary HL.
Manipulations of the sensory environment typically induce greater changes to the developing nervous system than they do in adulthood. The relevance of these neural changes can be evaluated by examining the age-dependent effects of sensory experience on quantitative measures of perception. Here, we measured frequency modulation (FM) detection thresholds in adult gerbils and investigated whether diminished auditory experience during development or in adulthood influenced perceptual performance. Bilateral conductive hearing loss (CHL) of ≈30 dB was induced either at postnatal day 10 or after sexual maturation. All animals were then trained as adults to detect a 5 Hz FM embedded in a continuous 4 kHz tone. FM detection thresholds were defined as the minimum deviation from the carrier frequency that the animal could reliably detect. Normal-hearing animals displayed FM thresholds of 25 Hz. Inducing CHL, either in juvenile or adult animals, led to a deficit in FM detection. However, this deficit was greater for juvenile onset hearing loss (89 Hz) relative to adult onset hearing loss (64 Hz). The effects could not be attributed to sensation level, nor were they correlated with proxies for attention. The thresholds displayed by CHL animals were correlated with shallower psychometric function slopes, suggesting that hearing loss was associated with greater variance of the decision variable, consistent with increased internal noise. The results show that decreased auditory experience has a greater impact on perceptual skills when initiated at an early age and raises the possibility that altered development of CNS synapses may play a causative role.
Key points
Severe forms of hearing loss during development are well known to profoundly alter synaptic structure and function through the auditory neuraxis; however, the pre‐ and postsynaptic modifications that occur during development following moderate forms of unilateral hearing loss remain unknown.
We performed anatomical and electrophysiological experiments at the calyx of Held synapse in slices taken from mature mice developing with a unilateral conductive hearing loss and compared populations of synapses in the same animal that were either sound deprived or sound experienced.
Compared to normal hearing mice, we found that calyx of Held synapses that were both sound deprived and sound experienced as a result of a unilateral conductive hearing loss were (1) structurally more complex, (2) had smaller synaptic currents and a readily releasable pool size, and (3) were more excitable.
Despite these changes in structure and function, spiking fidelity within the populations maintained a continuum as in normal hearing mice such that heterogeneities remained bilaterally symmetric.
Preservations in the heterogeneity in spiking fidelity via synaptic remodelling may ensure that a functional stability important for the ability to code sound localization cues is maintained despite asymmetries in hearing experience during development.
Abstract
Structure and function of central synapses are profoundly influenced by experience during developmental sensitive periods. Sensory synapses, which are the indispensable interface for the developing brain to interact with its environment, are particularly plastic. In the auditory system, moderate forms of unilateral hearing loss during development are prevalent but the pre‐ and postsynaptic modifications that occur when hearing symmetry is perturbed are not well understood. We investigated this issue by performing experiments at the large calyx of Held synapse. Principal neurons of the medial nucleus of the trapezoid body (MNTB) are innervated by calyx of Held terminals that originate from the axons of globular bushy cells located in the contralateral ventral cochlear nucleus. We compared populations of synapses in the same animal that were either sound deprived (SD) or sound experienced (SE) after unilateral conductive hearing loss (CHL). Middle ear ossicles were removed 1 week prior to hearing onset (approx. postnatal day (P) 12) and morphological and electrophysiological approaches were applied to auditory brainstem slices taken from these mice at P17–19. Calyces in the SD and SE MNTB acquired their mature digitated morphology but these were structurally more complex than those in normal hearing mice. This was accompanied by bilateral decreases in initial EPSC amplitude and synaptic conductance despite the CHL being unilateral. During high‐frequency stimulation, some SD synapses displayed short‐term depression whereas others displayed short‐term facilitation followed by slow depression similar to the heterogeneities observed in normal hearing mice. However SE synapses predominantly displayed short‐term facilitation followed by slow depression which could be explained in part by the decrease in release probability. Furthermore, the excitability of principal cells in the SD MNTB had increased significantly. Despite these unilateral changes in short‐term plasticity and excitability, heterogeneities in the spiking fidelity among the population of both SD and SE synapses showed similar continuums to those in normal hearing mice. Our study suggests that preservations in the heterogeneity in spiking fidelity via synaptic remodelling ensures symmetric functional stability which is probably important for retaining the capability to maximally code sound localization cues despite moderate asymmetries in hearing experience.
Although protective effects of the cochlea's efferent feedback pathways have been well documented, prior work has focused on hair cell damage and cochlear threshold elevation and, correspondingly, on the high sound pressure levels (>100 dB SPL) necessary to produce them. Here we explore the noise-induced loss of cochlear neurons that occurs with lower-intensity exposures and in the absence of permanent threshold shifts. Using confocal microscopy to count synapses between hair cells and cochlear nerve fibers, and using measurement of auditory brainstem responses and otoacoustic emissions to assess cochlear presynaptic and postsynaptic function, we compare the damage from a weeklong exposure to moderate-level noise (84 dB SPL) in mice with varying degrees of cochlear de-efferentation induced by surgical lesion to the olivocochlear pathway. Such exposure causes minimal acute threshold shifts and no chronic shifts in mice with normal efferent feedback. In de-efferented animals, there was up to 40% loss of cochlear nerve synapses and a corresponding decline in the amplitude of the auditory brainstem response. Quantitative analysis of the de-efferentation in inner versus outer hair cell areas suggested that outer hair cell efferents are the most important in minimizing this neuropathy, presumably by virtue of their sound-evoked feedback reduction of cochlear amplification. The moderate nature of this acoustic overexposure suggests that cochlear neurons are at risk even in everyday acoustic environments, so the need for cochlear protection is plausible as a driving force in the design of this feedback pathway.
Behavioral adaption to a changing environment is critical for an animal's survival. How well the brain can modify its functional properties based on experience essentially defines the limits of behavioral adaptation. In adult animals the extent to which experience shapes brain function has not been fully explored. Moreover, the perceptual consequences of experience-induced changes in the brains of adults remain unknown. Here we show that the tonotopic map in the primary auditory cortex of adult rats living with low-level ambient noise underwent a dramatic reorganization. Behaviorally, chronic noise-exposure impaired fine, but not coarse pitch discrimination. When tested in a noisy environment, the noise-exposed rats performed as well as in a quiet environment whereas the control rats performed poorly. This suggests that noise-exposed animals had adapted to living in a noisy environment. Behavioral pattern analyses revealed that stress or distraction engendered by the noisy background could not account for the poor performance of the control rats in a noisy environment. A reorganized auditory map may therefore have served as the neural substrate for the consistent performance of the noise-exposed rats in a noisy environment.
The acoustic rearing environment can alter central auditory coding properties, yet altered neural coding is seldom linked with specific deficits to adult perceptual skills. To test whether developmental hearing loss resulted in comparable changes to perception and sensory coding, we examined behavioral and neural detection thresholds for sinusoidally amplitude modulated (sAM) stimuli. Behavioral sAM detection thresholds for slow (5 Hz) modulations were significantly worse for animals reared with bilateral conductive hearing loss (CHL), as compared to controls. This difference could not be attributed to hearing thresholds, proficiency at the task, or proxies for attention. Detection thresholds across the groups did not differ for fast (100 Hz) modulations, a result paralleling that seen in humans. Neural responses to sAM stimuli were recorded in single auditory cortex neurons from separate groups of awake animals. Neurometric analyses indicated equivalent thresholds for the most sensitive neurons, but a significantly poorer detection threshold for slow modulations across the population of CHL neurons as compared to controls. The magnitude of the neural deficit matched that of the behavioral differences, suggesting that a reduction of sensory information can account for limitations to perceptual skills.
Synapses formed by one cell type onto another cell type tend to show characteristic short-term plasticity, which varies from facilitating to depressing depending on the particular system. Within a population of synapses, plasticity can also be variable, and it is unknown how this plasticity is determined on a cell-by-cell level. We have investigated this in the mouse cochlear nucleus, where auditory nerve (AN) fibers contact bushy cells (BCs) at synapses called "endbulbs of Held." Synapses formed by different AN fibers onto one BC had plasticity that was more similar than would be expected at random. Experiments using MK-801 indicated that this resulted in part from similarity in the presynaptic probability of release. The similarity was not present in immature synapses but emerged after the onset of hearing. In addition, the phenomenon occurred at excitatory synapses in the cerebellum. This indicates that postsynaptic cells coordinate the plasticity of their inputs, which suggests that plasticity is of fundamental importance to synaptic function.
Plasticity in the medial and lateral olivocochlear (MOC and LOC) systems in response to chronic exposure to background noise was investigated. Three different age-groups of young mice were exposed to the same chronic moderate noise conditions with either immediate tissue harvest or harvest following restoration to quiet conditions, with age matched controls. Cochleae were dissected and standard immunohistochemistry protocols were used to label hair cells with antibodies against myosin 6 and olivocochlear synaptic terminals with synaptic vesicle protein 2 (SV2). Specimens were imaged using confocal microscopy, and density of SV2 labeling was quantified. There was no statistically significant difference in MOC SV2 density between mice raised in noise and age matched controls for any group. However, there was a statistically significant increase in LOC SV2 density for adult mice raised in noise, particularly at higher frequency regions. This could suggest a protective upregulation of the efferent system against chronic moderate noise exposure. The increase in LOC innervation persisted for juvenile mice raised in noise with subsequent restoration to quiet conditions. These data suggest that the LOC system demonstrates sound-dependent plasticity, but that synaptic morphology may be altered for a substantial time period after exposure to noise ceases.
The anatomy and physiology of olivocochlear (OC) efferents are reviewed. To help interpret these, recent advances in cochlear mechanics are also reviewed. Lateral OC (LOC) efferents innervate primary auditory-nerve (AN) fiber dendrites. The most important LOC function may be to reduce auditory neuropathy. Medial OC (MOC) efferents innervate the outer hair cells (OHCs) and act to turn down the gain of cochlear amplification. Cochlear amplification had been thought to act only through basilar membrane (BM) motion, but recent reports show that motion near the reticular lamina (RL) is amplified more than BM motion, and that RL-motion amplification extends to several octaves below the local characteristic frequency. Data on efferent effects on AN-fiber responses, otoacoustic emissions (OAEs) and human psychophysics are reviewed and reinterpreted in the light of the new cochlear-mechanical data. The possible origin of OAEs in RL motion is considered. MOC-effect measuring methods and MOC-induced changes in human responses are also reviewed, including that ipsilateral and contralateral sound can produce MOC effects with different patterns across frequency. MOC efferents help to reduce damage due to acoustic trauma. Many, but not all, reports show that subjects with stronger contralaterally-evoked MOC effects have better ability to detect signals (e.g. speech) in noise, and that MOC effects can be modulated by attention.
Objectives/hypothesis:
To define the clinical features and natural history of pediatric tinnitus from a practicing otolaryngologist's perspective and formulate hypotheses therein.
Study design:
Retrospective chart review.
Methods:
A retrospective chart review of the electronic medical record was undertaken. Only relevant records with a prior otolaryngology clinic visit and audiologic testing were included. Patients seen during the last 2 years of the study period were contacted and completed a questionnaire to assess change in tinnitus and quantify potential alterations in quality of life, associated symptoms, and natural history.
Results:
One hundred eighty subjects with mean/median age of 11.5/11.5 years were identified. Hearing loss was identified in 40 subjects (22.2%). Etiology of tinnitus was identified in 95 subjects (52.8 %). Tinnitus-specific and/or nonspecific therapies were given to 80 subjects (44.4%). Of the 54 available subjects, 28 (51.9%) participated in the telephone questionnaire. Tinnitus complaints shifted favorably to the improvement or resolution categories (P = .001) between the initial clinic visit and the telephone interview. Shorter duration of tinnitus was associated with a higher probability of having improved tinnitus (P = .046).
Conclusions:
This study distinguishes pediatric tinnitus from adult tinnitus in terms of lower association with underlying hearing loss, lower likelihood of reported anxiety, and higher likelihood of improvement and resolution. There are opportunities for tinnitus prevention in the areas of reducing head injury and noise-induced hearing loss.
Level of evidence:
4 Laryngoscope, 2017.
Objectives/hypothesis:
Medications for pediatric tinnitus are not widely used due to a lack of evidence-based information. The modification of risk factors is essential in pediatric tinnitus; however, there is a lack of systematic reviews despite several reports on risk factors. This study performed a systematic review and meta-analysis of available literature to evaluate risk factors of pediatric tinnitus.
Methods:
Studies reporting the risk factors of pediatric tinnitus were systematically reviewed by searching the MEDLINE, PubMed, and Embase databases for studies published from database inception to 2016. The selected articles included clinical or epidemiological studies conducted with at least 50 subjects and at least one risk factor, including age, gender, hearing loss, noise exposure, or smoking.
Results:
Eleven studies involving a total of 28,358 individuals were identified. Increased age was not a significant risk factor with a standardized median difference of 0.16 (95% confidence interval [CI]: -0.01 to 0.33). However, there was a significant correlation between increased age and tinnitus in the adolescent population. The odds ratio (OR) was 1.37 for female gender (95% CI: 1.17 to 1.60), 2.39 for hearing loss (95% CI: 1.48 to 3.87), and 11.35 for noise exposure (95% CI: 1.87 to 68.77). Two studies in adolescents showed statistical significance for smoking as a risk factor in developing tinnitus (OR: 6.05, 95% CI: 1.81 to 20.21).
Conclusions:
Older-aged adolescents, as well as those who are females and those with hearing loss may have a higher risk of tinnitus. Noise exposure in the general pediatric population and smoking in adolescents may represent especially important risk factors in pediatric tinnitus. Laryngoscope, 2017.
This investigation compared the development of neuronal excitability in the ventral nucleus of the trapezoid body (VNTB) between two strains of mice with differing progression rates for age-related hearing loss. In contrast to CBA/Ca (CBA) mice, the C57BL/6J (C57) strain are subject to hearing loss from a younger age and are more prone to damage from sound over-exposure. Higher firing rates in the medial olivocochlear system (MOC) are associated with protection from loud sounds and these cells are located in the VNTB. We postulated that reduced neuronal firing of the MOC in C57 mice could contribute to hearing loss in this strain by reducing efferent protection. Whole cell patch clamp was used to compare the electrical properties of VNTB neurons from the two strains initially in two age groups: before and after hearing onset at ∼ P9 and ∼P16, respectively. Prior to hearing onset VNTB neurons electrophysiological properties were identical in both strains, but started to diverge after hearing onset. One week after hearing onset VNTB neurons of C57 mice had larger amplitude action potentials but in contrast to CBA mice, their waveform failed to accelerate with increasing age, consistent with the faster inactivation of voltage-gated potassium currents in C57 VNTB neurons. The lower frequency action potential firing of C57 VNTB neurons at P16 was maintained to P28, indicating that this change was not a developmental delay. We conclude that C57 VNTB neurons fire at lower frequencies than in the CBA strain, supporting the hypothesis that reduced MOC firing could contribute to the greater hearing loss of the C57 strain.
The consequences of developmental hearing loss have been reported to include both sensory and cognitive deficits. To investigate these issues in a non-human model, auditory learning and asymptotic psychometric performance were compared between normal hearing (NH) adult gerbils and those reared with conductive hearing loss (CHL). At postnatal day 10, before ear canal opening, gerbil pups underwent bilateral malleus removal to induce a permanent CHL. Both CHL and control animals were trained to approach a water spout upon presentation of a target (Go stimuli), and withhold for foils (Nogo stimuli). To assess the rate of task acquisition and asymptotic performance, animals were tested on an amplitude modulation (AM) rate discrimination task. Behavioral performance was calculated using a signal detection theory framework. Animals reared with developmental CHL displayed a slower rate of task acquisition for AM discrimination task. Slower acquisition was explained by an impaired ability to generalize to newly introduced stimuli, as compared to controls. Measurement of discrimination thresholds across consecutive testing blocks revealed that CHL animals required a greater number of testing sessions to reach asymptotic threshold values, as compared to controls. However, with sufficient training, CHL animals approached control performance. These results indicate that a sensory impediment can delay auditory learning, and increase the risk of poor performance on a temporal task.
Unlabelled:
Sensory pathways display heightened plasticity during development, yet the perceptual consequences of early experience are generally assessed in adulthood. This approach does not allow one to identify transient perceptual changes that may be linked to the central plasticity observed in juvenile animals. Here, we determined whether a brief period of bilateral auditory deprivation affects sound perception in developing and adult gerbils. Animals were reared with bilateral earplugs, either from postnatal day 11 (P11) to postnatal day 23 (P23) (a manipulation previously found to disrupt gerbil cortical properties), or from P23-P35. Fifteen days after earplug removal and restoration of normal thresholds, animals were tested on their ability to detect the presence of amplitude modulation (AM), a temporal cue that supports vocal communication. Animals reared with earplugs from P11-P23 displayed elevated AM detection thresholds, compared with age-matched controls. In contrast, an identical period of earplug rearing at a later age (P23-P35) did not impair auditory perception. Although the AM thresholds of earplug-reared juveniles improved during a week of repeated testing, a subset of juveniles continued to display a perceptual deficit. Furthermore, although the perceptual deficits induced by transient earplug rearing had resolved for most animals by adulthood, a subset of adults displayed impaired performance. Control experiments indicated that earplugging did not disrupt the integrity of the auditory periphery. Together, our results suggest that P11-P23 encompasses a critical period during which sensory deprivation disrupts central mechanisms that support auditory perceptual skills.
Significance statement:
Sensory systems are particularly malleable during development. This heightened degree of plasticity is beneficial because it enables the acquisition of complex skills, such as music or language. However, this plasticity comes with a cost: nervous system development displays an increased vulnerability to the sensory environment. Here, we identify a precise developmental window during which mild hearing loss affects the maturation of an auditory perceptual cue that is known to support animal communication, including human speech. Furthermore, animals reared with transient hearing loss display deficits in perceptual learning. Our results suggest that speech and language delays associated with transient or permanent childhood hearing loss may be accounted for, in part, by deficits in central auditory processing mechanisms.
Hearing loss among the elderly correlates with diminished social, mental, and physical health. Age-related cochlear cell death does occur, but growing anatomical evidence suggests that synaptic rearrangements on sensory hair cells also contribute to auditory functional decline. Here we present voltage-clamp recordings from inner hair cells of the C57BL/6J mouse model of age-related hearing loss, which reveal that cholinergic synaptic inputs re-emerge during aging. These efferents are functionally inhibitory, using the same ionic mechanisms as do efferent contacts present transiently before the developmental onset of hearing. The strength of efferent inhibition of inner hair cells increases with hearing threshold elevation. These data indicate that the aged cochlea regains features of the developing cochlea and that efferent inhibition of the primary receptors of the auditory system re-emerges with hearing impairment.
Synaptic changes in the auditory periphery are increasingly recognized as important factors in hearing loss. To date, anatomical work has described the loss of afferent contacts from cochlear hair cells. However, relatively little is known about the efferent innervation of the cochlea during hearing loss. We performed intracellular recordings from mouse inner hair cells across the lifespan and show that efferent innervation of inner hair cells arises in parallel with the loss of afferent contacts and elevated hearing threshold during aging. These efferent neurons inhibit inner hair cells, raising the possibility that they play a role in the progression of age-related hearing loss.
Copyright © 2015 the authors 0270-6474/15/359701-06$15.00/0.
Significance
Synapses with high probability of neurotransmitter release ( P r ) depress during prolonged activity, which reduces the faithful transfer of information. Auditory nerve synapses onto bushy cells show particularly strong depression at physiologically relevant rates of activity, which raises the question of how bushy cells transmit information when sound levels are high for a prolonged period. After rearing mice in constant, nondamaging noise, auditory nerve synapses changed from high to low P r , with a corresponding increase in the number of release sites, which increased spike fidelity during high activity. Neither quantal size nor average excitatory postsynaptic current changed. After returning to control conditions, P r recovered to high. These changes seem to reflect a homeostatic response to enhance fidelity.
Cochlear activity is regulated by the olivo-cochlear bundle, which originates from the brainstem and projects onto the hair cells and auditory nerve fibers. Two efferent components can be distinguished: the medial and lateral olivo-cochlear efferent originating from the medial, and the lateral nuclei of the superior olivary complex. The input of the efferent systems on hair cells occurs during development and persists in the adult cochlea. Recent studies have shown that the efferent innervations are required to set the activity pattern in developing hair cells and auditory nerve fibers and to protect the synaptic structures in adult cochlea. In addition, efferent innervations undergo plasticity during pathological conditions such as noise-trauma or aging. This review discusses the mechanisms underlying the control of the hair cells and afferent fibers excitability by efferent neurons and their putative role in developing adult and pathological conditions.
Tinnitus and hyperacusis, commonly seen in adults, are also reported in children. Although clinical studies found children with tinnitus and hyperacusis often suffered from recurrent otitis media, there is no direct study on how temporary hearing loss in the early age affects the sound loudness perception. In this study, sound loudness changes in rats affected by perforation of the tympanic membranes (TM) have been studied using an operant conditioning based behavioral task. We detected significant increases of sound loudness and susceptibility to audiogenic seizures (AGS) in rats with bilateral TM damage at postnatal 16 days. As increase to sound sensitivity is commonly seen in hyperacusis and tinnitus patients, these results suggest that early age hearing loss is a high risk factor to induce tinnitus and hyperacusis in children. In the TM damaged rats, we also detected a reduced expression of GABA receptor δ and α6 subunits in the inferior colliculus (IC) compared to the controls. Treatment of vigabatrin (60 mg/kg/day, 7-14 days), an anti-seizure drug that inhibits the catabolism of GABA, not only blocked AGS, but also significantly attenuated the loudness response. Administration of vigabatrin following the early age TM damage could even prevent rats from developing AGS. These results suggest that TM damage at an early age may cause a permanent reduction of GABA tonic inhibition which is critical towards the maintenance of normal loudness processing of the IC. Increasing GABA concentration during the critical period may alleviate the impairment in the brain induced by early age hearing loss.
The physiology of the efferent cochlear innervation and the pathophysiology of tinnitus are 2 important but rather obscure chapters of neuro-otology. The possible interference of the medial olivocochlear bundle (MOCB) in the pathophysiology of tinnitus is not only a matter of strong controversy but also a field with possible important clinical and therapeutic implications. The aim of this study was to reveal the differences in study population, design, and methodology that may have attributed the conflicting results in the existing clinical trials.
A review of the relevant literature published between January 1990 and June 2013 was conducted via the PubMed database (www.pubmed.org) with the search terms "tinnitus" and "otoacoustic emissions and suppression or efferent."
Clinical studies on patients with additional pathologic abnormalities that may implicate the MOCB, such as hyperacousis or auditory neuropathy, were excluded.
The 15 relevant studies were reviewed for critical differences in the recruitment of their study population and control group, as well as their methods of testing and evaluating the results.
The different methods and study parameters are compared to each other. Factors known to attribute different MOCB responses, possibly responsible for the controversial results, are highlighted.
The remarkable heterogeneity of the existing studies does not allow for safe conclusions. Insufficient knowledge on the physiology of the MOCB reflex seems to preclude the formation of a consensus on the optimal protocol for the evaluation of its function. Further research is definitely needed.
The role of the corticofugal efferent auditory system in the origin or maintenance of tinnitus is currently mostly overlooked. Changes in the balance between excitation and inhibition after an auditory trauma are likely to play a role in the origin of tinnitus. The efferent auditory system can be expected to be involved in such changes.
The goal of this article was to investigate the current knowledge of the functional efferent auditory system in humans, mostly based on animal research, and to look for new possibilities to try to answer the question of the specific role(s) of the corticofugal efferent auditory system in tinnitus.
Literature review.
Several suggestions for future research are made, for studies in humans as well as in animals.
We think that it will be worthwhile to investigate the efferent auditory system and its relations to tinnitus in the near future. With this article, we hope to inspire such work.
Endbulb of Held terminals of auditory nerve fibers (ANF) transmit auditory information at hundreds per second to bushy cells (BCs) in the anteroventral cochlear nucleus (AVCN). Here, we studied the structure and function of endbulb synapses in mice that lack the presynaptic scaffold bassoon and exhibit reduced ANF input into the AVCN. Endbulb terminals and active zones were normal in number and vesicle complement. Postsynaptic densities, quantal size and vesicular release probability were increased while vesicle replenishment and the standing pool of readily releasable vesicles were reduced. These opposing effects canceled each other out for the first evoked EPSC, which showed unaltered amplitude. We propose that ANF activity deprivation drives homeostatic plasticity in the AVCN involving synaptic upscaling and increased intrinsic BC excitability. In vivo recordings from individual mutant BCs demonstrated a slightly improved response at sound onset compared to ANF, likely reflecting the combined effects of ANF convergence and homeostatic plasticity. Further, we conclude that bassoon promotes vesicular replenishment and, consequently, a large standing pool of readily releasable synaptic vesicles at the endbulb synapse.
Acoustic overexposure can cause a permanent loss of auditory nerve fibers without destroying cochlear sensory cells, and despite complete recovery of cochlear thresholds (Kujawa and Liberman, 2009), as measured by gross neural potentials such as the auditory brainstem response (ABR). To address this nominal paradox, we recorded responses from single auditory nerve fibers in guinea pigs exposed to this type of neuropathic noise (4-8 kHz octave band at 106 dB SPL for 2 hrs). Two weeks post exposure, ABR thresholds had recovered to normal, while suprathreshold ABR amplitudes were reduced. Both thresholds and amplitudes of distortion-product otoacoustic emissions fully recovered, suggesting recovery of hair cell function. Loss of up to 30% of auditory-nerve synapses on inner hair cells was confirmed by confocal analysis of the cochlear sensory epithelium imunostained for pre- and post-synaptic markers. In single-fiber recordings, at two weeks post-exposure, frequency tuning, dynamic range, post-onset adaptation, first-spike latency and its variance, and other basic properties of auditory nerve response were all completely normal in the remaining fibers. The only physiological abnormality was a change in population statistics suggesting a selective loss of fibers with low- and medium- spontaneous rates. Selective loss of these high-threshold fibers would explain how ABR thresholds can recover despite such significant noise-induced neuropathy. A selective loss of high-threshold fibers may contribute the problems hearing in noisy environments that characterize the aging auditory system.
To date, the functional and physiological impact on the mature brain of moderate-level environmental noises that do not cause noticeable peripheral deficits remains largely unstudied. Here we show that exposing adult rats to structured noise at a sound pressure level of 65 dB, which is markedly below the broadly accepted safety level standard, results in behavioural impairments and substantially impairs the function of the auditory cortex. The strong deterioration in cortical processing of acoustic inputs is independent of the modulation rates of structured noises. Almost equally strong effects result from 10-h daily versus 24-h daily exposure regimens. These results indicate that there can be substantial negative consequences for the auditory system documented at the cortical level, attributable to environmental exposure to structured noises delivered under conditions that do not directly impact hearing sensitivity. These noises are deemed to be 'safe' and are often present in modern human environments.
Early experience of structured inputs and complex sound features generate lasting changes in tonotopy and receptive field properties of primary auditory cortex (A1). In this study we tested whether these changes are severe enough to alter neural representations and behavioral discrimination of speech. We exposed two groups of rat pups during the critical period of auditory development to pulsed-noise or speech. Both groups of rats were trained to discriminate speech sounds when they were young adults, and anesthetized neural responses were recorded from A1. The representation of speech in A1 and behavioral discrimination of speech remained robust to altered spectral and temporal characteristics of A1 neurons after pulsed-noise exposure. Exposure to passive speech during early development provided no added advantage in speech sound processing. Speech training increased A1 neuronal firing rate for speech stimuli in naïve rats, but did not increase responses in rats that experienced early exposure to pulsed-noise or speech. Our results suggest that speech sound processing is resistant to changes in simple neural response properties caused by manipulating early acoustic environment.
It has become increasingly clear that even occasional exposure to loud sounds in occupational or recreational settings can cause irreversible damage to the hair cells of the cochlea and the auditory nerve fibers, even if the resulting partial loss of hearing sensitivity, usually accompanied by tinnitus, disappears within hours or days of the exposure. Such exposure may explain at least some cases of poor speech intelligibility in noise in the face of a normal or near-normal audiogram. Recent findings from our laboratory suggest that long-term changes to auditory brain function-potentially leading to problems with speech intelligibility-can be effected by persistent, passive exposure to more moderate levels of noise (in the 70 dB SPL range) in the apparent absence of damage to the auditory periphery (as reflected in normal distortion product otoacoustic emissions and auditory brainstem responses). Specifically, passive exposure of adult cats to moderate levels of band-pass-filtered noise, or to band-limited ensembles of dense, random tone pips, can lead to a profound decrease of neural activity in the auditory cortex roughly in the exposure frequency range, and to an increase of activity outside that range. This can progress to an apparent reorganization of the cortical tonotopic map, which is reminiscent of the reorganization resulting from hearing loss restricted to a part of the hearing frequency range, although again, no hearing loss was apparent after our moderate-level sound exposure. Here, we review this work focusing specifically on the potential hearing problems that may arise despite a normally functioning auditory periphery.
Tinnitus perception depends on the presence of its neural correlates within the auditory neuraxis and associated structures. Targeting specific circuits and receptors within the central nervous system in an effort to relieve the perception of tinnitus and its impact on one's emotional and mental state has become a focus of tinnitus research. One approach is to upregulate endogenous inhibitory neurotransmitter levels (e.g., glycine and GABA) and selectively target inhibitory receptors in key circuits to normalize tinnitus pathophysiology. Thus, the basic functional and molecular properties of two major ligand-gated inhibitory receptor systems, the GABA(A) receptor (GABA(A)R) and glycine receptor (GlyR) are described. Also reviewed is the rationale for targeting inhibition, which stems from reported tinnitus-related homeostatic plasticity of inhibitory neurotransmitter systems and associated enhanced neuronal excitability throughout most central auditory structures. However, the putative role of the medial geniculate body (MGB) in tinnitus has not been previously addressed, specifically in terms of its inhibitory afferents from inferior colliculus and thalamic reticular nucleus and its GABA(A)R functional heterogeneity. This heterogeneous population of GABA(A)Rs, which may be altered in tinnitus pathology, and its key anatomical position in the auditory CNS make the MGB a compelling structure for tinnitus research. Finally, some selective compounds, which enhance tonic inhibition, have successfully ameliorated tinnitus in animal studies, suggesting that the MGB and, to a lesser degree, the auditory cortex may be their primary locus of action. These pharmacological interventions are examined in terms of their mechanism of action and why these agents may be effective in tinnitus treatment. This article is part of a Special Issue entitled Tinnitus Neuroscience.