Biased synaptopathy as a central mechanism of age-related hearing loss.
Different properties of sounds are encoded by different subcortical circuits. Real-time auditory scene analysis requires multiple parallel streams of information encoded by these circuits to converge at the auditory cortex, forming auditory objects in space (Bregman 1994). This process begins at the cochlear nucleus (CN). As the first central auditory station, the CN receives information about sounds from the spiral ganglion neurons (SGNs) via the central synapses formed by the auditory nerve fibres (ANFs). A number of cell types exist in the CN, each of which assumes specialized morphology and physiology suitable for extracting certain features of sounds. Bushy cells are specialized in receiving and transmitting temporal information, which is critical for sound localization and speech comprehension. Much effort has been devoted to revealing the details of innervation in bushy cells, although the level of resolution has been limited by the lack of appropriate tools to distinguish different fibre types. In this issue of The Journal of Physiology, taking advantage of the molecular markers for distinct presynaptic fibres originating from the SGNs, Wang et al. (2021) investigated explicitly the innervation impinging upon single bushy cells in the mouse CN.
Lu Y
The Journal Of Physiology
2021
2021-01-31
<table width="91" style="border-collapse:collapse;width:68pt;"><colgroup><col width="91" style="width:68pt;" /></colgroup><tbody><tr style="height:15pt;"><td width="91" height="20" class="xl18" style="width:68pt;height:15pt;"><a href="http://doi.org/10.1113/JP281348">http://doi.org/10.1113/JP281348</a></td>
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Binaural interaction of bone-conducted auditory brainstem responses in children with congenital atresia of the external auditory canal.
Adolescent; Audiometry; Auditory; Bilateral/congenital/physiopathology; Bone Conduction/*physiology; Brain Stem/*physiology; Child; Conductive/congenital/physiopathology; Ear; Ear Canal/*abnormalities/physiopathology; Evoked Potentials; Evoked Response; Hearing Loss; Humans; Middle/abnormalities; Preschool; Pure-Tone; Temporal Bone/abnormalities
Bilateral bone-conducted auditory brainstem responses (BC-ABRs) were recorded in children with atresia of the external auditory canal bilaterally (AECB) in order to compare the response characteristics to normal hearing adults. The binaural interaction component (BIC) of the ABR occurs when the sum of the monaural-evoked ABR amplitudes are different in amplitude when compared to the binaural-evoked ABR amplitude. Previous electrophysiological work from our lab has shown that children with AECB lateralize bone-conducted (BC) sound. Furthermore, we have found in normal-hearing adults that BICs exist using BC clicks. In adults, BC-BIC occurred in the latency region corresponding to waves IV-VI, whereas for children with AECB corresponding peak latencies occurred earlier. Same as normal-hearing adults, BC-ABR IV-V complex peak amplitudes for sum of the BC-monaural right and
Sheykholeslami Kianoush; Habiby Kermany Mohammad; Sebastein Schmerber; Kaga Kimitaka
International journal of pediatric otorhinolaryngology
2003
2003-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s0165-5876(03)00197-6" target="_blank" rel="noreferrer noopener">10.1016/s0165-5876(03)00197-6</a>
Brain microvascular pathology in Susac syndrome: an electron microscopic study of five cases
hearing loss; Susac syndrome; electron microscopy; encephalopathy; branch retinal artery occlusion; cerebral vasculitis; corpus callosal lesions
Susac syndrome is a rare, immune-mediated disease characterized by encephalopathy, branch retinal artery occlusion, and hearing loss. Herein, we describe the electron microscopic findings of three brain biopsies and two brain autopsies performed on five patients whose working clinical diagnosis was Susac syndrome. In all five cases, the key findings were basement membrane thickening and collagen deposition in the perivascular space involving small vessels and leading to thickening of vessel walls, narrowing, and vascular occlusion. These findings indicate that Susac syndrome is a microvascular disease. Mononuclear cells were present in the perivascular space, underlining the inflammatory nature of the pathology. Though nonspecific, the changes can be distinguished from genetic and acquired small vessel diseases. The encephalopathy of Susac syndrome overlaps clinically with degenerative and infectious conditions, and brain biopsy may be used for its diagnosis. Its vascular etiology may not be obvious on light microscopy, and electron microscopy is important for its confirmation.
Agamanolis Dimitri P; Prayson Richard A; Asdaghi Negar; Gultekin Sakir H; Bigley Kim; Rennebohm Robert M
Ultrastructural Pathology
2019
2019-11-16
Journal Article
<a href="http://doi.org/10.1080/01913123.2019.1692117" target="_blank" rel="noreferrer noopener">10.1080/01913123.2019.1692117</a>
PMID: 31736417
Diminished behavioral and neural sensitivity to sound modulation is associated with moderate developmental hearing loss.
Female; Male; Animals; Gerbillinae; *Attention; *Behavior; Neurons; Animal; Hearing Loss; Afferent/pathology; Conductive/pathology/*physiopathology
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.
Rosen Merri J; Sarro Emma C; Kelly Jack B; Sanes Dan H
PloS one
2012
1905-7
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1371/journal.pone.0041514" target="_blank" rel="noreferrer noopener">10.1371/journal.pone.0041514</a>
Homozygosity for a mutation affecting the catalytic domain of tyrosyl-tRNA synthetase (YARS) causes multisystem disease
Adult; Biochemistry & Molecular Biology; Catalytic Domain; Child; Female; gene; Genetic Diseases; Genetic Predisposition to Disease; Genetics & Heredity; Hearing Loss; Heterozygote; Homozygote; Humans; impairment; Inborn; Infant; lactic-acidosis; Loss of Function Mutation; Male; mechanisms; Mutation; myopathy; Newborn; onset; Pedigree; Phenotype; phenotypic variability; Preschool; recessive mutations; Sensorineural; Severity of Illness Index; swiss-model; Tyrosine-tRNA Ligase; variant; Whole Exome Sequencing; Yeasts
Aminoacyl-tRNA synthetases (ARSs) are critical for protein translation. Pathogenic variants of ARSs have been previously associated with peripheral neuropathy and multisystem disease in heterozygotes and homozygotes, respectively. We report seven related children homozygous for a novel mutation in tyrosyl-tRNA synthetase (YARS, c.499C > A, p.Pro167Thr) identified by whole exome sequencing. This variant lies within a highly conserved interface required for protein homodimerization, an essential step in YARS catalytic function. Affected children expressed a more severe phenotype than previously reported, including poor growth, developmental delay, brain dysmyelination, sensorineural hearing loss, nystagmus, progressive cholestatic liver disease, pancreatic insufficiency, hypoglycemia, anemia, intermittent proteinuria, recurrent bloodstream infections and chronic pulmonary disease. Related adults heterozygous for YARS p.Pro167Thr showed no evidence of peripheral neuropathy on electromyography, in contrast to previous reports for other YARS variants. Analysis of YARS p.Pro167Thr in yeast complementation assays revealed a loss-of-function, hypomorphic allele that significantly impaired growth. Recombinant YARS p.Pro167Thr demonstrated normal subcellular localization, but greatly diminished ability to homodimerize in human embryonic kidney cells. This work adds to a rapidly growing body of research emphasizing the importance of ARSs in multisystem disease and significantly expands the allelic and clinical heterogeneity of YARS-associated human disease. A deeper understanding of the role of YARS in human disease may inspire innovative therapies and improve care of affected patients.
Williams Katie B; Brigatti Karlla W; Puffenberger Erik G; Gonzaga-Jauregui Claudia; Griffin Laurie B; Martinez Erick D; Wenger Olivia K; Yoder Mark A; Kandula Vinay V R; Fox Michael D; Demczko Matthew M; Poskitt Laura; Furuya Katryn N; Reid Jeffrey G; Overton John D; Baras Aris; Miles Lili; Radhakrishnan Kadakkal; Carson Vincent J; Antonellis Anthony; Jinks Robert N; Strauss Kevin A
Human Molecular Genetics
2019
1905-7
<a href="http://doi.org/10.1093/hmg/ddy344" target="_blank" rel="noreferrer noopener">10.1093/hmg/ddy344</a>
Noise-induced cochlear synaptopathy: Past findings and future studies.
*Auditory Perception; *Hearing; *Hearing loss; *Molecular approach; *Preclinical model; *Spiral ganglion; *Synaptic loss; *Synaptic Transmission; Animals; Auditory; Hair Cells; Hearing Loss; Hearing Tests; Humans; Inner/*pathology; Noise-Induced/diagnosis/*pathology/physiopathology/psychology; Noise/*adverse effects; Predictive Value of Tests; Psychoacoustics; Spiral Ganglion/*pathology/physiopathology; Synapses/*pathology
For decades, we have presumed the death of hair cells and spiral ganglion neurons are the main cause of hearing loss and difficulties understanding speech in noise, but new findings suggest synapse loss may be the key contributor. Specifically, recent preclinical studies suggest that the synapses between inner hair cells and spiral ganglion neurons with low spontaneous rates and high thresholds are the most vulnerable subcellular structures, with respect to insults during aging and noise exposure. This cochlear synaptopathy can be "hidden" because this synaptic loss can occur without permanent hearing threshold shifts. This new discovery of synaptic loss opens doors to new research directions. Here, we review a number of recent studies and make suggestions in two critical future research directions. First, based on solid evidence of cochlear synaptopathy in animal models, it is time to apply molecular approaches to identify the underlying molecular mechanisms; improved understanding is necessary for developing rational, effective therapies against this cochlear synaptopathy. Second, in human studies, the data supporting cochlear synaptopathy are indirect although rapid progress has been made. To fully identify changes in function that are directly related this hidden synaptic damage, we argue that a battery of tests including both electrophysiological and behavior tests should be combined for diagnosis of "hidden hearing loss" in clinical studies. This new approach may provide a direct link between cochlear synaptopathy and perceptual difficulties.
Kobel Megan; Le Prell Colleen G; Liu Jennifer; Hawks John W; Bao Jianxin
Hearing research
2017
2017-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.heares.2016.12.008" target="_blank" rel="noreferrer noopener">10.1016/j.heares.2016.12.008</a>
Variable Effects of Acoustic Trauma on Behavioral and Neural Correlates of Tinnitus In Individual Animals.
inferior colliculus; gap-induced prepulse inhibition of the acoustic startle reflex; hearing loss; prepulse audiometry; single unit recording; tinnitus
The etiology of tinnitus is known to be diverse in the human population. An appropriate animal model of tinnitus should incorporate this pathological diversity. Previous studies evaluating the effect of acoustic over exposure (AOE) have found that animals typically display increased spontaneous firing rates and bursting activity of auditory neurons, which often has been linked to behavioral evidence of tinnitus. However, only a subset of studies directly associated these neural correlates to individual animals. Furthermore, the vast majority of tinnitus studies were conducted on anesthetized animals. The goal of this study was to test for a possible relationship between tinnitus, hearing loss, hyperactivity and bursting activity in the auditory system of individual unanesthetized animals following AOE. Sixteen mice were unilaterally exposed to 116 dB SPL narrowband noise (centered at 12.5 kHz) for 1 h under ketamine/xylazine anesthesia. Gap-induced prepulse inhibition of the acoustic startle reflex (GPIAS) was used to assess behavioral evidence of tinnitus whereas hearing performance was evaluated by measurements of auditory brainstem response (ABR) thresholds and prepulse inhibition PPI audiometry. Following behavioral assessments, single neuron firing activity was recorded from the inferior colliculus (IC) of four awake animals and compared to recordings from four unexposed controls. We found that AOE increased spontaneous activity in all mice tested, independently of tinnitus behavior or severity of threshold shifts. Bursting activity did not increase in two animals identified as tinnitus positive (T+), but did so in a tinnitus negative (T-) animal with severe hearing loss (SHL). Hyperactivity does not appear to be a reliable biomarker of tinnitus. Our data suggest that multidisciplinary assessments on individual animals following AOE could offer a powerful experimental tool to investigate mechanisms of tinnitus.
Longenecker Ryan J; Galazyuk Alexander V
Frontiers in behavioral neuroscience
2016
1905-7
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.3389/fnbeh.2016.00207" target="_blank" rel="noreferrer noopener">10.3389/fnbeh.2016.00207</a>
Vestibular-evoked myogenic potentials in three patients with large vestibular aqueduct.
Adult; Auditory Threshold/*physiology; Auditory/*physiology; Bilateral/diagnosis/etiology; Child; Evoked Potentials; Female; Hearing Loss; Humans; Preschool; Saccule and Utricle/*physiopathology; Sensorineural/diagnosis/etiology; Tomography; Vestibular Aqueduct/*abnormalities/*physiopathology; Vestibular Diseases/complications/congenital/*physiopathology; Vestibular Function Tests; X-Ray Computed
An enlarged vestibular aqueduct (LVA) is a common congenital inner ear anomaly responsible for some unusual vestibular and audiological symptoms. Most of the cases show bilateral early onset and progressive hearing loss in children. The gross appearance on CT scan of the inner ear is generally normal. However, precise measurements of the inner ear components reveal abnormal dimensions, which may account for the accompanying auditory and vestibular dysfunction. Despite extensive studies on hearing and the vestibular apparatus, saccular function is not studied. To our knowledge this is the first report of saccular malfunction in three patients with LVA by means of vestibular evoked myogenic potentials. Conventional audiograms revealed bilateral severe sensorineural hearing loss in two patients and mixed type hearing loss in one patient. Two of the patients complained about vertigo and dizziness but vestibular assessments of the patients showed normal results. The diagnosis had been made by high-resolution CT scans and MR images of the skull that showed LVA in the absence of other anomalies. The VEMP threshold measured from the ear with LVA in two patients with unilateral enlargement of the vestibular aqueduct was 75-80 dB nHL whereas the threshold from normal ears was 95 dB nHL. The third patient with mixed type hearing loss and bilateral LVA had VEMP responses despite a big air-bone gap in the low frequency range. The VEMP in this patient was greater in amplitude and lower in threshold in the operated ear (the patient had a tympanoplasty which did not improve her hearing). These findings and results of other patients with Tullio phenomenon and superior semicircular canal dehiscence, who also showed lower VEMP threshold, confirmed the theory of a 'third window' that allows volume and pressure displacements, and thus larger deflection of the vestibular sensors, which would cause the vestibular organ to be more responsive to sound and pressure changes.
Sheykholeslami Kianoush; Schmerber Sebastien; Habiby Kermany Mohammad; Kaga Kimitaka
Hearing research
2004
2004-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/S0378-5955(04)00018-8" target="_blank" rel="noreferrer noopener">10.1016/S0378-5955(04)00018-8</a>