Tectorial Research Articles

A model for the relation between stimulus frequency and spontaneous otoacoustic emissions in lizard papillae

Spontaneous otoacoustic emissions (SOAEs) and stimulus frequency otoacoustic emissions (SFOAEs) have been described from lizard ears. Although there are several models for these systems, none has modeled the characteristics of both of these types of otoacoustic emissions based upon their being derived from hair cells as active oscillators. Data from the ears of two lizard species, one lacking a tectorial membrane and one with a chain of tectorial sallets, as described by Bergevin et al. ["Coupled, active oscillators and lizard otoacoustic emissions," AIP Conf. Proc. 1403, 453 (2008)], are modeled as an array of coupled self-sustained oscillators. The model, originally developed by Vilfan and Duke ["Frequency clustering in spontaneous otoacoustic emissions from a lizard's ear," Biophys. J. 95, 4622-4630 (2008)], well describes both the amplitude and phase characteristics of SFOAEs and the relation between SFOAEs and SOAEs.

Mutations of the Gene Encoding Otogelin Are a Cause of Autosomal-Recessive Nonsyndromic Moderate Hearing Impairment

Already 40 genes have been identified for autosomal-recessive nonsyndromic hearing impairment (arNSHI); however, many more genes are still to be identified. In a Dutch family segregating arNSHI, homozygosity mapping revealed a 2.4 Mb homozygous region on chromosome 11 in p15.1-15.2, which partially overlapped with the previously described DFNB18 locus. However, no putative pathogenic variants were found in USH1C, the gene mutated in DFNB18 hearing impairment. The homozygous region contained 12 additional annotated genes including OTOG, the gene encoding otogelin, a component of the tectorial membrane. It is thought that otogelin contributes to the stability and strength of this membrane through interaction or stabilization of its constituent fibers. The murine orthologous gene was already known to cause hearing loss when defective. Analysis of OTOG in the Dutch family revealed a homozygous 1bp deletion, c.5508delC, which leads to a shift in the reading frame and a premature stop codon, p.Ala1838ProfsX31. Further screeningof 60 unrelated probands from Spanish arNSHI families detected compound heterozygous OTOG mutations in one family, c.6347C>T (p.Pro2116Leu) and c. 6559C>T (p.Arg2187X). The missense mutation p.Pro2116Leu affects a highly conserved residue in the fourth von Willebrand factor type D domain of otogelin. The subjects with OTOG mutations have a moderate hearing impairment, which can be associated with vestibular dysfunction. The flat to shallow "U" or slightly downsloping shaped audiograms closely resembled audiograms of individuals with recessive mutations in the gene encoding α-tectorin, another component of the tectorial membrane. This distinctive phenotype may represent a clue to orientate the molecular diagnosis.

Modeling normal and hearing-impaired monaural and binaural signal detection in the presence of noise

Psychoacoustical investigations have demonstrated that monaural and binaural signal detection is affected by existence of distracting noise. The most prominent phenomena are co-modulation masking release (CMR) in monotic listening, and binaural masking level difference (BMLD) in diotic listening. Both CMR and BMLD are significantly deteriorates in hearing-impaired listeners. Both CMR and BMLD phenomena are tested by a complete model of the auditory system for normal and hearing-impaired systems. Prediction of the amplitude discrimination results are obtained by deriving the Cramer Rao lower bound (CRLB) of the neural activity. The auditory system model includes a complete cochlear model with integrated outer hair cells and tectorial membrane; an inner hair cell-synapse model that transduce the cilia motion to auditory nerve instantaneous rate; Inferior Colliculus that receives inputs from both ears and process them by excitatory-inhibitory (EI) cells. The AN activity is considered as a non-homogeneous Poisson process (NHHP). We have recently showed that EI cells are NHHP as well, if their inputs behave as NHHP. Therefore, CRLB can be derived analytically from both AN and IC outputs. We have successfully predicted major CMR and BMLD properties as a function of frequency and noise properties for normal and impaired auditory system.

Vestibular System Changes in Sudden Deafness With and Without Vertigo

To investigate the vestibular system changes in sudden deafness with vertigo (SDwV) and sudden deafness without vertigo (SDwoV) and the cause of persistent canal paresis (CP) in SDwV patients. Retrospective study. Four temporal bones from the affected ear in 4 patients with unilateral sudden deafness (SD), 2 SDwV and 2 SDwoV, were selected. Four contralateral temporal bones with normal-hearing ears were defined as the control. Morphologic findings of the labyrinth, the number of Scarpa's ganglion cells, and the density of vestibular hair cells were investigated in all temporal bones. Clinical data and the results of vestibular tests of 11 patients with unilateral SD, as a separate group, also were investigated. Atrophic change of the organ of Corti, tectorial membrane, and stria vascularis in cochlea, and deposits and atrophic otoconial membrane in vestibular sense organs were seen on affected ears more than control ears. The density of Type I hair cells seemed to decrease on the saccular macula and the posterior semicircular canal crista on affected ears, and there was no remarkable difference between SDwV and SDwoV. In 1 patient with SDwoV who died 10 months after the onset of SD, there were large amount of deposits on the cupula, the atrophied otoconial membrane was peeling off from the saccular macula, and the saccular membrane collapsed to the saccular macula in the affected ear. In the clinical data, all SDwV who were examined within 2 years from the onset had CP, and all SDwV had profound hearing loss. There is no remarkable difference between SDwV and SDwoV in the number of Scarpa's ganglion cells and the density of vestibular hair cells. The damage of the extracellular superstructure is seen in SD with or without vertigo. The damage of extracellular superstructure is potentially one of the causes of persistent CP in patients with SD.

How are inner hair cells stimulated? Evidence for multiple mechanical drives

Recent studies indicate that the gap over outer hair cells (OHCs) between the reticular lamina (RL) and the tectorial membrane (TM) varies cyclically during low-frequency sounds. Variation in the RL-TM gap produces radial fluid flow in the gap that can drive inner hair cell (IHC) stereocilia. Analysis of RL-TM gap changes reveals three IHC drives in addition to classic SHEAR. For upward basilar-membrane (BM) motion, IHC stereocilia are deflected in the excitatory direction by SHEAR and OHC-MOTILITY, but in the inhibitory direction by TM-PUSH and CILIA-SLANT. Upward BM motion causes OHC somatic contraction which tilts the RL, compresses the RL-TM gap over IHCs and expands the RL-TM gap over OHCs, thereby producing an outward (away from the IHCs) radial fluid flow which is the OHC-MOTILITY drive. For upward BM motion, the force that moves the TM upward also compresses the RL-TM gap over OHCs causing inward radial flow past IHCs which is the TM-PUSH drive. Motions that produce large tilting of OHC stereocilia squeeze the supra-OHC RL-TM gap and caused inward radial flow past IHCs which is the CILIA-SLANT drive. Combinations of these drives explain: (1) the reversal at high sound levels of auditory nerve (AN) initial peak (ANIP) responses to clicks, and medial olivocochlear (MOC) inhibition of ANIP responses below, but not above, the ANIP reversal, (2) dips and phase reversals in AN responses to tones in cats and chinchillas, (3) hypersensitivity and phase reversals in tuning-curve tails after OHC ablation, and (4) MOC inhibition of tail-frequency AN responses. The OHC-MOTILITY drive provides another mechanism, in addition to BM motion amplification, that uses active processes to enhance the output of the cochlea. The ability of these IHC drives to explain previously anomalous data provides strong, although indirect, evidence that these drives are significant and presents a new view of how the cochlea works at frequencies below 3 kHz.

Audiometric characteristics of two Dutch families with non-ocular Stickler syndrome (COL11A2)

ObjectiveTo evaluate hearing impairment and cochlear function in non-ocular Stickler syndrome. Study designMultifamily study. Patients & methodsTen patients from two different families with non-ocular Stickler syndrome (Stickler syndrome type 3) were included. Six members of the first family and four members of the second family participated in this study. Otorhinolaryngologic examinations were performed. Pure-tone and speech audiograms were obtained. Longitudinal analysis was performed. Psychophysical measurements, including loudness scaling, gap detection, difference limen for frequency and speech perception in noise were administered to assess cochlear function at a deeper level. ResultsAffected individuals in the first family were carriers of a heterozygous splice donor mutation in the COL11A2 gene. Affected individuals in the second family were carriers of a novel heterozygous missense mutation in COL11A2. Both families showed bilateral, non-progressive hearing impairment with childhood onset. The severity of the hearing impairment exhibited inter- and intrafamilial variability and was mostly mild to moderate. The results of the psychophysical measurements were similar to those previously published for DFNA8/12 (TECTA) and DFNA13 (COL11A2) patients and thus consistent with an intra-cochlear conductive hearing impairment. This is in line with the theory that mutations in COL11A2 affect tectorial membrane function. ConclusionHearing impairment in non-ocular Stickler syndrome is characterized by non-progressive hearing loss, present since childhood, and mostly mild to moderate in severity. Psychophysical measurements in non-ocular Stickler patients were suggestive of intra-cochlear conductive hearing impairment.

MAGNETIC RESONANCE IMAGING OF THE LIGAMENTOUS STRUCTURES OF THE OCCIPITOATLANTOAXIAL REGION IN THE DOG

Our objectives were to establish a magnetic resonance (MR) protocol for the examination of, and then describe, the normal ligaments and the supporting structures of the occipitoatlantoaxial region. This was done in 10 cadaver dogs. In addition, MR images of three patients with cervical pain localized to the occipitoatlantoaxial region are included to provide examples of ligamentous abnormalities. All ligaments were hypointense in all pulse sequences. The apical, dorsal atlantoaxial, and dorsal longitudinal vertebral ligaments were seen best in the sagittal T1W and PD-weighted images. The transverse ligament was best visualized in the transverse plane in all pulse sequences and appeared to be confluent with the dorsal longitudinal vertebral ligament dorsal to the dens in the sagittal plane. A 20° dorsal plane reconstructed image in 0.6-mm slice thickness was necessary to visualize the alar ligaments, which were visible in 9/10 dogs. The dorsal longitudinal vertebral ligament appeared continuous with the apical ligament and tectorial membrane. Abnormalities in clinically affected dogs included thickening of the alar ligaments, absence of transverse ligament and elongation, and irregularity of the apical ligament.

TECTA mutations in Japanese with mid-frequency hearing loss affected by zona pellucida domain protein secretion

TECTA gene encodes α-tectorin, the major component of noncollagenous glycoprotein of the tectorial membrane, and has a role in intracochlear sound transmission. The TECTA mutations are one of the most frequent causes of autosomal dominant (AD) hearing loss and genotype-phenotype correlations are associated with mutations of TECTA in exons according to α-tectorin domains. In this study, we investigated the prevalence of hearing loss caused by TECTA mutations in Japanese AD hearing loss families, and confirmed genotype-phenotype correlation, as well as the intracellular localization of missense mutations in the α-tectorin domain. TECTA mutations were detected in 2.9% (4/139) of our Japanese AD hearing loss families, with the prevalence in moderate hearing loss being 7.7% (4/52), and all patients showed typical genotype-phenotype correlations as previously described. The present in vitro study showed differences of localization patterns between wild type and mutants, and suggested that each missense mutation may lead to a lack of assembly of secretion, and may reduce the incorporation of α-tectorin into the tectorial membrane.

Loss of Mammal-specific Tectorial Membrane Component Carcinoembryonic Antigen Cell Adhesion Molecule 16 (CEACAM16) Leads to Hearing Impairment at Low and High Frequencies

The vertebrate-restricted carcinoembryonic antigen gene family evolves extremely rapidly. Among their widely expressed members, the mammal-specific, secreted CEACAM16 is exceptionally well conserved and specifically expressed in the inner ear. To elucidate a potential auditory function, we inactivated murine Ceacam16 by homologous recombination. In young Ceacam16(-/-) mice the hearing threshold for frequencies below 10 kHz and above 22 kHz was raised. This hearing impairment progressed with age. A similar phenotype is observed in hearing-impaired members of Family 1070 with non-syndromic autosomal dominant hearing loss (DFNA4) who carry a missense mutation in CEACAM16. CEACAM16 was found in interdental and Deiters cells and was deposited in the tectorial membrane of the cochlea between postnatal days 12 and 15, when hearing starts in mice. In cochlear sections of Ceacam16(-/-) mice tectorial membranes were significantly more often stretched out as compared with wild-type mice where they were mostly contracted and detached from the outer hair cells. Homotypic cell sorting observed after ectopic cell surface expression of the carboxyl-terminal immunoglobulin variable-like N2 domain of CEACAM16 indicated that CEACAM16 can interact in trans. Furthermore, Western blot analyses of CEACAM16 under reducing and non-reducing conditions demonstrated oligomerization via unpaired cysteines. Taken together, CEACAM16 can probably form higher order structures with other tectorial membrane proteins such as α-tectorin and β-tectorin and influences the physical properties of the tectorial membrane. Evolution of CEACAM16 might have been an important step for the specialization of the mammalian cochlea, allowing hearing over an extended frequency range.

Estimation of optimal insertion angle in a mammalian outer hair cell stereocilium

Optimal insertion angle of mammalian stereocilia is estimated from the finite element analysis of the tip motion of outer hair cells (OHCs) stereocilia. The OHC stereocilia motion in the acousticolateral system appears to result in the mechanoelectrical transduction channels. Deflection of the hair bundle towards the tallest row of stereocilia causes increased probability of opening of ion channels. In this work, we focus on one of the physical features of the OHC stereocilium, the initial insertion angle of the tallest row into the tectorial membrane (TM), and its effects on the stereocilia's deflection motion. A three-dimensional model was built for the tallest stereocilium and the TM at the region where the best frequency was 500Hz. The mechanical interactions between the embedded stereocilia and the TM have been implemented into the finite element simulation. We found that, the optimum insertion angle of the tallest stereocilium into the TM was 69.8°, where the stereocilium is maximally deflected. This quantity is consistent with the histological observation obtained from the literature.

The anterior shear and distraction tests for craniocervical instability. An evaluation using magnetic resonance imaging

Screening for integrity of the ligaments of the craniocervical complex has been suggested prior to the application of manual techniques to the upper cervical spine. However, most tests proposed lack validation limiting their usefulness clinically. This study examined the effect of the anterior shear test for the transverse ligament and the distraction test for the tectorial membrane in normal volunteers. MRI was performed in supine in neutral and end-range stress test positions in 16 individuals using proton density-weighted sequences and a standard head coil in a 3-T system. Measurements were made with respect to a strictly standardised protocol. The anterior shear test was assessed using changes in atlantodental interval and distance from the anterior arch of the atlas to the posterior aspect of the odontoid process. Distraction testing for the tectorial membrane was assessed by changes in basion-dental interval and by direct measurement of the tectorial membrane. Differences were compared using Wilcoxon Sign Rank tests or paired t-test depending upon each variables assessment of normality. Anterior shear testing resulted in a 0.41 mm mean increase in atlantodental interval (p = 0.03) and 0.35 mm mean increase in axial plane distance (p = 0.05). Distraction testing for the tectorial membrane resulted in a 0.64 mm increase in basion-dental interval (p < 0.01) and a 1.11 mm increase in direct ligament length measurement (p = 0.02). Reliability of measurements ranged from moderate to substantial. These results indicate that these tests produce a consistent direct effect on the transverse ligament and the tectorial membrane which is consistent with their theorised mechanism for clinical use.

Quantitative X-ray Tomography of the Mouse Cochlea

Imaging with hard X-rays allows visualizing cochlear structures while maintaining intrinsic qualities of the tissue, including structure and size. With coherent X-rays, soft tissues, including membranes, can be imaged as well as cells making use of the so-called in-line phase contrast. In the present experiments, partially coherent synchrotron radiation has been used for micro-tomography. Three-dimensional reconstructions of the mouse cochlea have been created using the EM3D software and the volume has been segmented in the Amira Software Suite. The structures that have been reconstructed include scala tympani, scala media, scala vestibuli, Reissner's membrane, basilar membrane, tectorial membrane, organ of Corti, spiral limbus, spiral ganglion and cochlear nerve. Cross-sectional areas of the scalae were measured. The results provide a realistic and quantitative reconstruction of the cochlea.

Response to a Pure Tone in a Nonlinear Mechanical-Electrical-Acoustical Model of the Cochlea

In this article, a nonlinear mathematical model is developed based on the physiology of the cochlea of the guinea pig. The three-dimensional intracochlear fluid dynamics are coupled to a micromechanical model of the organ of Corti and to electrical potentials in the cochlear ducts and outer hair cells (OHC). OHC somatic electromotility is modeled by linearized piezoelectric relations whereas the OHC hair-bundle mechanoelectrical transduction current is modeled as a nonlinear function of the hair-bundle deflection. The steady-state response of the cochlea to a single tone is simulated in the frequency domain using an alternating frequency time scheme. Compressive nonlinearity, harmonic distortion, and DC shift on the basilar membrane (BM), tectorial membrane (TM), and OHC potentials are predicted using a single set of parameters. The predictions of the model are verified by comparing simulations to available in vivo experimental data for basal cochlear mechanics. In particular, the model predicts more amplification on the reticular lamina (RL) side of the cochlear partition than on the BM, which replicates recent measurements. Moreover, small harmonic distortion and DC shifts are predicted on the BM, whereas more significant harmonic distortion and DC shifts are predicted in the RL and TM displacements and in the OHC potentials.

Pediatric atlanto-occipital dissociation: radiographic findings and clinical outcome

Study design: Retrospective diagnostic feasibility study and clinical review.Objectives: To evaluate the feasibility of making an initial atlanto-occipital dissociation (AOD) diagnosis from four radiological measurements of the craniocervical relationship on lateral cervical spine x-rays and to assess the AOD patients' clinical outcomes relative to their magnetic resonance imaging (MRI) findings.Methods: The Powers ratio, Wackenheim line, basion-dens distance (BDD), and the C1/2:C2/3 interspinous ratio were measured in 58 pediatric controls and ten MRI-confirmed patients with AOD. The ability to identify the required anatomical landmarks and make the measurements was noted and sensitivity and specificity calculated. The correspondence between the clinical presentation and outcomes for patients with AOD and their MRI features was investigated.Results: Clear landmarks for measuring interspinous ratio and Wackenheim line were confirmed by all x-rays. The BDD was measureable in 90% and the Powers ratio could be calculated in only possible in 59%. The interspinous ratio and BDD offered high sensitivities and specificity. Although the Wackenheim line was consistantly measured, it conferred a low sensitivity but reasonable specificity. The Powers ratio offered high specificity with low sensitivity. On MRI, all patients with AOD had apical ligament disruption, with a high rate of interspinous ligamentous injury (8/9); prevertebral swelling (7/9); retroclival hematoma (6/9); and tectorial membrane injury (4/9). The only MRI feature associated with poor outcome was that of altered cord signal. Both patients who died had cord signal changes on T1- and T2-weighted images. The third patient with cord signal change was limited to T2 changes with a normal T1. He had a C5-L3 sensory deficit that resolved. The degree of tectorial membrane injury did not appear to influence outcome.Conclusions: The BDD and interspinous ratio offer the best measures for initial x-ray diagnosis of AOD. This will alert the surgeon to the need for MRI. These patients often have a reduced level of consciousness, thus making clinical evaluation difficult. The MRI findings, although apparently indicative of severe abnormality, did not actually correspond to outcomes except for the presence of T1 cord signal changes that matched with severe neurological impairment and subsequent death.

Toll-like receptor 2 and Toll-like receptor 4 participates in mediation of acute otitis media and mortality in pneumococcal infections in mice

To investigate the roles of Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) in host defense against Streptococcus pneumoniae infection in the middle ear. Wild-type (WT) C57BL/6J, TLR2-deficient (TLR2(-/-)) and TLR4-deficient (TLR4(-/-)) mice were inoculated with Streptococcus pneumoniae (1 × 10(6)CFU) through the tympanic membrane. All animals were tested the mouse ABR thresholds and tympanometry measurement before, and 1 day, 3 days and 7 days following pneumococcal challenge. Blood bacterial titer were determined by plating 50 µl volumes of 10-fold diluted blood. Histological analysis of middle ear and inner ear were performed by fixation, decalcification, embedded section, and counterstained with hematoxylin/eosin and toluidine blue staining. Semi-quantitative RT-PCR was applied to determine mRNA accumulation of TLR2 and TLR4 related genes. Forty of 68 TLR2(-/-) mice and twenty-one of 59 TLR4(-/-) mice showed bacteremia and died within 3 days after the pneumococcal challenge, however, only 9 of 52 WT mice died. The survive mice were shown have more severe hearing loss in the TLR2(-/-) and TLR4(-/-) mice than in the WT mice, indicated by ABR thresholds, at 3 or 7 days postinoculation. The histological pathology was characterized by effusion and tissue damage in the middle ear, and in the TLR2(-/-) and TLR4(-/-) mice, the outcome of infection became more severe at 7 days. At both 3 and 7 days after challenge, the TLR2(-/-) mice had higher blood bacterial titers than WT mice (P < 0.05). Temporal bone histopathologic change indicated that 3 days after the pneumococcal challenge, the TLR2(-/-) and TLR4(-/-) mice showed effusion and tissue damage in the middle ear, and the infection became more severe at 7 days postinoculation. TLR2(-/-) mice showed severe inflammatory cell infiltration in the cochlear, the organ of Corti showed the outer hair cells damage, the tectorial membrane swelling, degeneration of the stria vascularis, and severe loss of spiral ganglion cells; However, the WT mice was not found the cell infiltration and tissue damage in the cochlear, the organ of Corti shown normal of outer hair cells. Mast cells were not found in the middle ear mucosa of TLR2(-/-) mice, but in the TLR4(-/-) and WT mice, more mast cells were found in the middle ear mucosa of effusion ear by 3 and 7 days postchallenge. Moreover, by 3 days postchallenge, the mRNA accumulation levels of NF-κB, tumor necrosis factor alpha (TNFα), interleukin1β, MIP-1α, MUC5AC and MUC5B were significantly lower in the ears of TLR2(-/-) mice than that in WT and TLR4(-/-) mice. TLR2(-/-) mice may produce relatively low levels of proinflammatory cytokines following pneumococcal challenge, thus hindering the clearance of bacteria from the middle ear and leading to sepsis and high mortality rate. This study indicated that TLR2 and TLR4 are important in the molecular pathogenesis and host response to otitis media.

Hear, Hear! Thyroid Hormone Transporters in Cochlear Development

Hearing is one of the most sensitive functions controlled by thyroid hormone (TH). It therefore appears to be of utmost importance to define the transporters that mediate TH passage within the auditory system because mutations in specific TH transporter genes may be connected to pathological findings. In this issue of Endocrinology, Sharlin et al. (1) provide detailed information on the temporal and spatial expression pattern of several TH transporter candidates in the mouse cochlea where these transporters may act as decisive gatekeepers. These data not only enlarge our understanding about TH traffic and action in the hearing system but also establish a sound basis for further studies such as the analysis of TH transporter-deficient mice. The development of hearing in humans as well as in rodents is highly dependent on sufficient TH supply. TH deprivation particularly during late fetal and neonatal stages can result in hearing impairments or even in deafness if TH substitution is not instituted within a critical time window (2, 3). Consequently, hearing impairment is common in geographic areas with a prevalence of iodine deficiency and is also evident in various forms of thyroid disorders such as congenital hypothyroidism (4) or resistance to TH (5, 6). A major target of TH in the auditory system is the cochlea where TH promotes the terminal differentiation of a variety of cell types. In particular, TH regulates the remodeling of the greater epithelial ridge and the tectorial membrane as well as the differentiation of the sensory epithelium that contains the sound-transducing hair cells. During this complexprocessof cochleadifferentiation, the amount of T3 as the receptor active form of TH is intriguingly tightly regulated by the type 2 deiodinase (Dio2) and type 3 deiodinase (Dio3) (7). The latter enzyme, which inactivates T4 and T3 by inner ring deiodination, is predominantly expressed at late prenatal stages and is thought to prevent a premature stimulation of TH receptors (TR). Consequently, Dio3 knockout mice display an accelerated cochlea differentiation and auditory defects (8). In contrast, Dio2 exhibits outer ring deiodinase activity and is responsible for converting T4 to T3. The postnatal rise in Dio2 activity with a peak at d 7 leads to an amplification of the cochlear T3 levels particularly during the time period when the differentiation of the auditory system is most dependent on sufficient T3 supply (7). Accordingly, Dio2 knockout mice suffer from hearing loss as well, but in contrast to Dio3 / mice, they show a retarded cochlear development (9). In light of these findings, it appears not too surprising that mouse mutants deficient in TR display severe cochlear defects as well (10, 11). Another mechanism by which the amount of T3 can be locally controlled is a differential expression of TH transporters. Studies in mouse mutants have revealed that the inactivation of the TH transporter monocarboxylate transporter 8 [Mct8 (Slc16a2)] results in an impaired transport of T3 via the blood-brain barrier and, consequently, in a hypothyroid situation in the central nervous system (CNS) (12–14). Patients with inactivating mutations in the X-linked MCT8 gene suffer from a severe form of psychomotor retardation and neurological impairments indicating that the human brain may even be more dependent on MCT8 for mediating TH entry into the brain than the mouse CNS (15–17). Other transporters such as the organic anion transporting polypeptide-1c1 [Oatp1c1 (Slco1c1)], the monocarboxylate transporter Mct10 (Slc16a10), or the L-type amino acid transporters Lat1 (Slc7a5) and Lat2 (Slc7a8) have been discussed to contribute signif-

Vibration responses of the organ of Corti and the tectorial membrane to electrical stimulation

Coupling of somatic electromechanical force from the outer hair cells (OHCs) into the organ of Corti is investigated by measuring transverse vibration patterns of the organ of Cori and tectorial membrane (TM) in response to intracochlear electrical stimulation. Measurement places at the organ of Corti extend from the inner sulcus cells to Hensen's cells and at the lower (and upper) surface of the TM from the inner sulcus to the OHC region. These locations are in the neighborhood of where electromechanical force is coupled into (1) the mechanoelectrical transducers of the stereocilia and (2) fluids of the organ of Corti. Experiments are conducted in the first, second, and third cochlear turns of an in vitro preparation of the adult guinea pig cochlea. Vibration measurements are made at functionally relevant stimulus frequencies (0.48-68 kHz) and response amplitudes (<15 nm). The experiments provide phase relations between the different structures, which, dependent on frequency range and longitudinal cochlear position, include in-phase transverse motions of the TM, counterphasic transverse motions between the inner hair cell and OHCs, as well as traveling-wave motion of Hensen's cells in the radial direction. Mechanics of sound processing in the cochlea are discussed based on these phase relationships.

Inner ear morphological correlates of ultrasonic hearing in frogs

Three species of anuran amphibians (Odorrana tormota, Odorrana livida and Huia cavitympanum) have recently been found to detect ultrasounds. We employed immunohistochemistry and confocal microscopy to examine several morphometrics of the inner ear of these ultrasonically sensitive species. We compared morphological data collected from the ultrasound-detecting species with data from Rana pipiens, a frog with a typical anuran upper cut-off frequency of ∼3 kHz. In addition, we examined the ears of two species of Lao torrent frogs, Odorrana chloronota and Amolops daorum, that live in an acoustic environment approximating those of ultrasonically sensitive frogs. Our results suggest that the three ultrasound-detecting species have converged on small-scale functional modifications of the basilar papilla (BP), the high-frequency hearing organ in the frog inner ear. These modifications include: 1. reduced BP chamber volume, 2. reduced tectorial membrane mass, 3. reduced hair bundle length, and 4. reduced hair cell soma length. While none of these factors on its own could account for the US sensitivity of the inner ears of these species, the combination of these factors appears to extend their hearing bandwidth, and facilitate high-frequency/ultrasound detection. These modifications are also seen in the ears of O. chloronota, suggesting that this species is a candidate for high-frequency hearing sensitivity. These data form the foundation for future functional work probing the physiological bases of ultrasound detection by a non-mammalian ear.

Auditory mechanics of the tectorial membrane and the cochlear spiral

This review is timely and relevant because new experimental and theoretical findings suggest that cochlear mechanics from the nanoscale to the macroscale are affected by the mechanical properties of the tectorial membrane and the cochlea's spiral shape. Main tectorial membrane themes addressed in this review are composition and morphology, nanoscale mechanical interactions with the outer hair cell bundle, macroscale longitudinal coupling, fluid interaction with inner hair cell bundles, and macroscale dynamics and waves. Main cochlear spiral themes are macroscale, low-frequency energy focusing and microscale organ of Corti shear gain. Recent experimental and theoretical findings reveal exquisite sensitivity of cochlear mechanical performance to tectorial membrane structural organization, mechanics, and its positioning with respect to hair bundles. The cochlear spiral geometry is a major determinant of low-frequency hearing. These findings suggest a number of important research directions.

Temporal Bone Findings in a Case of Susac's Syndrome

To describe the histopathologic findings in the temporal bones of a patient with Susac's syndrome (SS). The key clinical features of SS consist of symptoms of encephalopathy, visual defects due to occlusion of branches of the retinal artery, and sensorineural hearing loss. The otopathology in SS has not been described. A 51-year-old woman was hospitalized with severe headache, rapidly progressive encephalopathy, and bilateral low-frequency sensorineural hearing loss. Magnetic resonance imaging showed lesions of the corpus callosum. Fluorescein angiography of the eyes showed focal areas of irregular retinal artery caliber and leakage from small vessels. SS was diagnosed. She died of a pulmonary embolus 1 month after onset of symptoms. Both temporal bones were prepared in celloidin and examined using light microscopy. Findings were nearly identical in both temporal bones. The apical halves of both cochleae showed widespread atrophy of structures of the cochlear duct (inner and outer hair cells, tectorial membranes, striae vasculares, spiral ligaments, and spiral limbi). The apical parts of both cochleae also showed apparent occlusion of capillaries within the stria vascularis and related areas of the cochlear duct. Cochlear neurons were present in normal numbers. There was no endolymphatic hydrops. The vestibular sense organs were normal for age. This first reported otopathologic case of SS with hearing loss showed atrophy and degeneration involving the apical halves of the cochlear duct without inflammation or infection. The findings were consistent with capillary occlusion as being responsible for the atrophy.