Saccular Macula Research Articles

Fgf, Hh, and pax2a differentially regulate expression of pax5 and pou3f3b in vestibular and auditory maculae in the zebrafish otic vesicle.

The vertebrate inner ear contains distinct sensory epithelia specialized for auditory or vestibular function. In zebrafish, the first sensory epithelia form at opposite ends of the otic vesicle and are functionally distinct: the anterior utricular macula is essential for vestibular function whereas the posterior saccular macula is critical for hearing. Mechanisms distinguishing these maculae are not clear. Here, we examined the effects of manipulating Fgf or Hh on expression of pax5 and pou3f3b, unique markers of utricular and saccular identity. We also examined the roles of pax2a and atoh1a/b, early regulators of sensory specification. fgf3 and fgf8a were uniquely required for pax5 and pou3f3b, respectively. Elevating Fgf or blocking Hh expanded expression of pax5 but repressed pou3f3b, while blocking Fgf had the opposite effect. Blocking sensory specification did not affect pax5 or pou3f3b, but both markers were lost in pax2a-/- mutants. Maintenance of pax2a expression requires Fgf, Hh and Pax2a itself. Specification of utricular identity requires high Fgf and is repressed by Hh, whereas saccular identity requires Hh plus low Fgf. pax2a acts downstream of Fgf and Hh to maintain both fates. Comparison with mouse suggests this may reflect a broadly conserved developmental mechanism.

Differential Expression of Na/K-ATPase in the Human Saccule of Patients With and Without Otologic Disease.

Na + , K + -ATPase (Na/K-ATPase) α1 subunit expression in the saccule of patients diagnosed with otologic disease is different compared with normal controls. We have recently characterized changes in the expression of Na/K-ATPase α1 subunit in the normal and pathological cochlea; however, no studies have determined the distribution Na/K-ATPase α1 subunit in the human saccule. The present study uses archival temporal bones to study the expression Na/K-ATPase α1 subunit in the human saccule. Archival celloidin formalin fixed 20-micron thick sections of the vestibule from patients diagnosed with Menière's disease (n = 5), otosclerosis (n = 5), sensorineural hearing loss, and normal hearing and balance (n = 5) were analyzed. Sections containing the saccular macula were immunoreacted with mouse monoclonal antibodies against Na/K-ATPase α1 subunit. Micrographs were acquired using a high-resolution digital camera coupled to a light inverted microscope. In the normal human saccule vestibular sensory epithelium, Na/K-ATPase α1 immunoreactivity (IR) was present in nerve fibers and calyces that surround type I vestibular hair cells and nerve terminals. The transition epithelium cells were also Na/K-ATPase α1 immunoreactive. Comparison between normal and pathological specimens showed that there was a significant reduction of Na/K-ATPase α1 IR in the saccule vestibular sensory epithelium from patients with Menière's disease, otosclerosis, and sensorineural hearing loss. The decrease of Na/K-ATPase-IR α1 in the saccule vestibular sensory epithelium from patients with otopathologies suggests its critical role in inner ear homeostasis and pathology.

Vestibular function for children with insulin dependent diabetes using cervical vestibular evoked myogenic potentials testing.

BACKGROUNDHealthy vestibular system adjusts balance during static and dynamic conditions. This is important for normal development (standing up and walking). Vestipulopathies (central and peripheral) are common complications of diabetes in adult population. Related studies are scare in children with type 1 diabetes (T1D). AIMTo assess saccular function of otolith organ in children with T1D and predictors for its dysfunction.METHODSCervical vestibular evoked myogenic potential (cVEMP) was used for objective evaluation. RESULTSThe study included 40 patients (boys = 15; girls = 25). Patients had mean age of 13.63 ± 1.50 years, duration of diabetes of 5.62 ± 2.80 years, frequent attacks of diabetic ketoacidosis (55%) and hypoglycemia (30%), hyperlipidemia (20%), hypertension (12.5%) and peripheral neuropathy (40%). Dizziness was found in 10%. Compared to healthy children (n = 25), patients had prolonged cVEMP P1 and N1 latencies and reduced P1-N1 amplitude. Bilateral cVEMP abnormalities were found in 60% (vs 25% for unilateral abnormalities). Higher frequencies and severe vestibulopathies were found with chronic diabetes of > 5 years, hemoglobin A1c values > 7%, frequent diabetic ketoacidosis and hypoglycemic attacks and presence of dizziness. Regression analyses showed that predictors for prolonged P1 latencies and reduced P1-N1 amplitudes were only chronic diabetes (> 5 years) {odds ratio (OR) = 2.80 [95% confidence interval (CI): 1.80–5.33], P = 0.01; OR = 3.42 (95%CI: 2.82–6.81)} and its severity (hemoglobin A1c > 7%) [OR = 3.05 (95%CI: 2.55–6.82), P = 0.01; OR = 4.20 (95%CI: 3.55–8.50), P = 0.001]. CONCLUSIONDysfunction or injury of the saccular macula and its pathways is prevalent in children with T1D. Optimum glycemic control is important to prevent diabetes related vestipulopathies.

A study of vestibular evoked myogenic potential and clinical features in benign paroxysmal positional vertigo: An institutional experience

Background: Benign paroxysmal positional vertigo (BPPV) is the most common vestibular disorder in adults caused by degeneration of the otolithic organs in most cases but may also be a consequence of head injury, labyrinthitis, and ischemia in the distribution of the anterior vestibular artery or prolonged bed rest. The aim of the study is to find the correlation of alterations in vestibular evoked myogenic potential (VEMP) recordings in BPPV patients, with other associated symptoms. Materials and Methods: The study was conducted in 29 BPPV patients over a 3-year period. All patients were investigated with pure-tone audiometry, bithermal caloric test with Electronystagmography (ENG) recording, and VEMP recording. Clinical tests included Romberg, Sharpened Romberg, and Dix–Hallpike tests. Associated parameters were recorded, and any association with abnormal VEMP was evaluated. Results: VEMP was abnormal in three patients. There was no association of abnormal p or n latency with BPPV. No significant relationship with any clinical parameter was observed. Conclusions: BPPV is associated with the occurrence of abnormal VEMP recordings, possibly due to degeneration of the saccular macula, but a reproducible association is not demonstrable in a significant way.

Three-Dimensional High-Resolution Temporal Bone Histopathology Identifies Areas of Vascular Vulnerability in the Inner Ear

Objectives: Hypothesized causes of vestibular neuritis/labyrinthitis include neuroinflammatory or vascular disorders, yet vascular disorders of the inner ear are poorly understood. Guided by known microvascular diseases of the retina, we developed 2 hypotheses: (1) there exist vascular vulnerabilities of artery channels in cases of hypothetical nerve swelling for the superior, inferior, and vestibulocochlear artery and (2) there are arteriovenous crossings that could compromise vascular flow in disease states. Methods: Two fully mounted and stained temporal bones were used to render three-dimensional reconstructions of the labyrinth blood supply. Using these maps, areas of potential vascular compression were quantified in 50 human temporal bones. Results: Although inner ear arteries and veins mostly travel within their own bony channels, they may be exposed (1) at the entrance into the otic capsule, and (2) where the superior vestibular vein crosses the inferior vestibular artery. At the entry into the otic capsule, the ratio of the soft tissue to total space for the superior vestibular artery was significantly greater than the inferior vestibular artery/cochleovestibular artery (median 44, interquartile range 34–55 vs. 14 [9–17], p < 0.0001). Conclusions: Three-dimensional reconstruction of human temporal bone histopathology can guide vascular studies of the human inner ear. Studies of retinal microvascular disease helped identify areas of vascular vulnerability in cases of hypothetical nerve swelling at the entrance into the otic capsule and at an arteriovenous crossing near the saccular macula. These data may help explain patterns of clinical findings in peripheral vestibular lesions.

Observation in inner ear of tree shrew using scanning electron microscope and the Atoh1 distribution in cochlea.

This study aimed to observe the ultrastructure on the surface of the inner ear of a normal tree shrew using scanning electron microscope (SEM). The specimens of cochlea, macula utriculi, macula sacculi, and crista ampullaris of the normal adult tree shrew were collected and observed by SEM. We used immunofluorescence for cochlear protein Atoh1 staining. We observed that cochlea of the tree shrew is centered on the cochlear axis, circling about 3.5 times from bottom to top of the cochlea. The organ of Corti is located between medial and lateral grooves, including inner and outer hair cells as well as supporting cells. Maculae staticae include macula of saccule and macula of utricle, and the surface of macula is covered with a large number of otoliths. We found a gelatinous layer below the otoliths, followed by the layer of the honeycomb structure. The hair cell cilia of macula and crista ampullaris include one kinocilium and more stereocilia. There is no obvious cross structure but numerous hair cell cilia on semicircular canal crista ampullaris. Immunofluorescence staining showed that protein Atoh1 is mainly distributed in the nucleus of the cochlea's inner and outer hair cells. The observation of the inner ear structure under SEM elucidate the fine surface morphological structure of the entire cochlea, the vestibular maculae staticae, and crista ampullaris, providing new insight into the structure and function of the inner ear of tree shrew. HIGHLIGHTS: This article is the first to describe the inner ear ultrastructure of a small primate tree shrew by scanning electron microscopy (SEM). Under an SEM, the phalangeal processes of Deiter cells in tree shrews were observed to be connected to the tip of a neighboring hair cell, which was different from that of Deiters' cells in guinea pigs, and this crossed one hair cell, and connected to the tip of the third hair cell. It was observed that the crista ampullaris of tree shrews were horseshoe-shaped, and similar to that of humans and monkeys, this had no obvious "cross-shaped hump" structure. Tree shrew's ABR threshold value curve conforms to the mammalian U-shaped curve, wave III is the main wave of ARB, its sensory frequency may be higher 8 kHz, and the characteristics of the stereocilia of tree shrew we have observed may be related to the perception of higher frequency hearing.

Sex Associated Effects of Noise Pollution in Stone Sculpin (Paracottus knerii) as a Model Object in the Context of Human-Induced Rapid Environmental Change.

Simple SummaryIn this comprehensive multidisciplinary study, we applied a novel multilevel approach to stone sculpins Paracottus knerii Dybowski, 1874, as model organisms and test for the first time the hypothesis of sex-dependent differences in response to long-term noise exposure in fish. The results testify that the stone sculpin females appeared to experience excessive stress, while the males showed adaptive recalibrations. These effects may be explained by a unique adaptive strategy of offspring care in the stone sculpin males and their biological role in reproductive behavior within the species. The findings obtained may help to elucidate the links between noise exposure in the context of human-induced rapid environmental change (HIREC), long-term sex-related changes in fishes, and the possible further evolutionary success of a species. Such HIREC modeling not only provides information about the potential consequences under anthropogenic pressure but also can help identify the natural mechanisms of stress resistance in different species, including those related to sex, and also contribute to the development of effective environmental management practices.This work simulates the consequences of HIREC using stone sculpins as model organisms. Sex-dependent effects of long-term noise exposure at mean sound pressure levels of 160–179 dB re 1 μPa (SPLpk–pk) were measured. We applied a multilevel approach to testing the stress response: a comparative analysis of the macula sacculi and an assessment of hematological and molecular stress responses. Noise exposure resulted in hair cell loss, changes in some cytometric parameters in blood, and an increase in the number of functionally active mitochondria in the red blood cells of males and its decrease in females, demonstrating a mitochondrial allostatic load and depletion of functional reserve. Finally, a statistically significant decrease in the telomerase activity of the auditory epithelium and a shortening of telomere length in the brain as molecular markers of stress were observed after noise exposure only in females. No significant decrease in telomerase activity and shortening of telomere length in nerve target tissues were observed in stressed males. However, we recorded an increase in the telomerase activity in male gonads. This sex-dependent difference in load may be associated with accelerated cellular aging in females and lower stress-related long-term risk in males. In this article, we discuss possible reasons for these noise-induced stress effects.

Evaluation of retrootolithic function using galvanic vestibular-evoked myogenic potentials in patients with benign paroxysmal positional vertigo

The purpose is to investigate possible vestibulopathy in patients with benign paroxysmal positional vertigo (BPPV), inner ear tests, including cervical and ocular vestibular-evoked myogenic potentials (cVEMPs and oVEMPs) via various stimulation modes, were adopted. Fifty BPPV patients were enrolled in this study. All patients underwent pure tone audiometry, cVEMPs, oVEMPs, and caloric tests. The recurrence status, abnormal rates of inner ear tests, and the characteristic parameters of VEMPs, such as wave latencies and amplitudes, were analyzed. In affected ears, the abnormal rates of acoustic cVEMPs, vibratory oVEMPs, galvanic cVEMPs, and galvanic oVEMPs were 62%, 28%, 36%, and 14%, respectively. The abnormalities of acoustic cVEMPs were significantly larger than those of vibratory oVEMPs, and acoustic/vibratory VEMPs had significantly higher abnormal rates than the corresponding galvanic VEMPs. BPPV patients may have both otolithic and neural dysfunctions. Otolithic organ damage occurs more frequently than retrootolithic neural degeneration, and the saccular macula might have a greater extent of damage than the utricular macula.

Calcium functional imaging with high-resolution CT in the inner ear

Although the otolith and otolith organs correlate with vertigo and instability, there is no method to investigate them without harmful procedures. We will create the technique for 3D microanatomical images of them, and investigate the in vivo internal state and metabolisms. The otolith and otolith organs images were reconstructed from a texture synthesis algorithm under the skull volume rendering algorithm using a cutting-plane method. The utricular macula was elongated pea-shaped. The saccular macula was almost bud-shaped. The changes in the amount of CaCO3 in the maculae and the endolymphatic sac showed various morphologies, reflecting the balance status of each subject. Both shapes and volumes were not always constant depending on time. In Meniere’s disease (MD), the saccular macula was larger and the utricular macula was smaller. In benign paroxysmal positional vertigo (BPPV), the otolith increased in the utricular macula but did not change much in the saccular macula. The saccule, utricle, and endolymphatic sac were not constantly shaped according to their conditions. These created 3D microanatomical images can allow detailed observations of changes in physiological and biological information. This imaging technique will contribute to our understanding of pathology and calcium metabolism in the in vivo vestibulum.

Calretinin Immunoreactivity in the VIIIth Nerve and Inner Ear Endorgans of Ranid Frogs.

Calcium-binding proteins are essential for buffering intracellular calcium concentrations, which are critical for regulating cellular processes involved in neuronal computations. One such calcium-binding protein, calretinin, is present in many neurons of the central nervous system as well as those which innervate cranial sensory organs, although often with differential distributions in adjacent cellular elements. Here, we determined the presence and distribution of calretinin-immunoreactivity in the peripheral vestibular and auditory system of ranid frogs. Calretinin-immunoreactivity was observed in ganglion cells innervating the basilar and amphibian papilla, and in a subpopulation of ganglion cells innervating the saccular epithelium. In contrast, none of the ganglion cells innervating the lagena, the utricle, or the three semicircular canals were calretinin-immunopositive, suggesting that this calcium-binding protein is a marker for auditory but not vestibular afferent fibers in the frog. The absence of calretinin in vestibular ganglion cells corresponds with the lack of type I hair cells in anamniote vertebrates, many of which in amniotes are contacted by the neurites of large, calyx-forming calretinin-immunopositive ganglion cells. In the sensory epithelia of all endorgans, the majority of hair cells were strongly calretinin-immunopositive. Weakly calretinin-immunopositive hair cells were distributed in the intermediate region of the semicircular canal cristae, the central part of the saccular macula, the utricular, and lagenar striola and the medial part of the amphibian papilla. The differential presence of calretinin in the frog vestibular and auditory sensory periphery might reflect a biochemical feature related to firing patterns and frequency bandwidths of self-motion versus acoustic stimulus encoding, respectively.

Endolymphatic Potential Measured From Developing and Adult Mouse Inner Ear.

The mammalian inner ear has two major parts, the cochlea is responsible for hearing and the vestibular organ is responsible for balance. The cochlea and vestibular organs are connected by a series of canals in the temporal bone and two distinct extracellular fluids, endolymph and perilymph, fill different compartments of the inner ear. Stereocilia of mechanosensitive hair cells in the cochlea and vestibular end organs are bathed in the endolymph, which contains high K+ ions and possesses a positive potential termed endolymphatic potential (ELP). Compartmentalization of the fluids provides an electrochemical gradient for hair cell mechanotransduction. In this study, we measured ELP from adult and neonatal C57BL/6J mice to determine how ELP varies and develops in the cochlear and vestibular endolymph. We measured ELP and vestibular microphonic response from saccules of neonatal mice to determine when vestibular function is mature. We show that ELP varies considerably in the cochlear and vestibular endolymph of adult mice, ranging from +95 mV in the basal turn to +87 mV in the apical turn of the cochlea, +9 mV in the saccule and utricle, and +3 mV in the semicircular canal. This suggests that ELP is indeed a local potential, despite the fact that endolymph composition is similar. We further show that vestibular ELP reaches adult-like magnitude around post-natal day 6, ~12 days earlier than maturation of cochlear ELP (i.e., endocochlear potential). Maturation of vestibular ELP coincides with the maturation of vestibular microphonic response recorded from the saccular macula, suggesting that maturation of vestibular function occurs much earlier than maturation of hearing in mice.

The Anatomical and Physiological Basis of Clinical Tests of Otolith Function. A Tribute to Yoshio Uchino.

Otolithic receptors are stimulated by gravitoinertial force (GIF) acting on the otoconia resulting in deflections of the hair bundles of otolithic receptor hair cells. The GIF is the sum of gravitational force and the inertial force due to linear acceleration. The usual clinical and experimental tests of otolith function have used GIFs (roll tilts re gravity or linear accelerations) as test stimuli. However, the opposite polarization of receptors across each otolithic macula is puzzling since a GIF directed across the otolith macula will excite receptors on one side of the line of polarity reversal (LPR at the striola) and simultaneously act to silence receptors on the opposite side of the LPR. It would seem the two neural signals from the one otolith macula should cancel. In fact, Uchino showed that instead of canceling, the simultaneous stimulation of the oppositely polarized hair cells enhances the otolithic response to GIF—both in the saccular macula and the utricular macula. For the utricular system there is also commissural inhibitory interaction between the utricular maculae in each ear. The results are that the one GIF stimulus will cause direct excitation of utricular receptors in the activated sector in one ear as well as indirect excitation resulting from the disfacilitation of utricular receptors in the corresponding sector on the opposite labyrinth. There are effectively two complementary parallel otolithic afferent systems—the sustained system concerned with signaling low frequency GIF stimuli such as roll head tilts and the transient system which is activated by sound and vibration. Clinical tests of the sustained otolith system—such as ocular counterrolling to roll-tilt or tests using linear translation—do not show unilateral otolithic loss reliably, whereas tests of transient otolith function [vestibular evoked myogenic potentials (VEMPs) to brief sound and vibration stimuli] do show unilateral otolithic loss. The opposing sectors of the maculae also explain the results of galvanic vestibular stimulation (GVS) where bilateral mastoid galvanic stimulation causes ocular torsion position similar to the otolithic response to GIF. However, GVS stimulates canal afferents as well as otolithic afferents so the eye movement response is complex.

Molecular and cellular responses to long-term sound exposure in peled (Coregonus peled).

This research examined the impacts of acoustic stress in peled (Coregonus peled Gmelin, 1788), a species commonly cultivated in Russia. This study presents a comparative analysis of the macula sacculi and otoliths, as well as primary hematological and secondary telomere stress responses, in control and sound-exposed peled. The authors measured the effects of long-term (up to 18 days) exposure to a 300 Hz tone at mean sound pressure levels of 176-186 dB re 1 μPa (SPLpk-pk); the frequency and intensity were selected to approximate loud acoustic environments associated with cleaning equipment in aquaculture settings. Acoustic exposure resulted in ultrastructure changes to otoliths, morphological damage to sensory hair cells of the macula sacculi, and a gradual decrease in the number of functionally active mitochondria in the red blood cells but no changes to telomeres. Changes were apparent following at least ten days of acoustic exposure. These data suggest that acoustic exposure found in some aquaculture settings could cause stress responses and auditory damage to peled and, potentially, other commercially important species. Reducing sound levels in fish rearing facilities could contribute to the formation of effective aquaculture practices that mitigate noise-induced stress in fishes.

Constant severe imbalance following traumatic otoconial loss: a new explanation of residual dizziness.

Benign paroxysmal positional vertigo (BPPV) is the most common type of vertigo, caused by otoconia falling from the utricle into a semicircular canal (SCC). After successful repositioning maneuvers residual dizziness (RD) has been described and several reasons are used to explain RD. It can last for only a few days or weeks, but also much longer. We present a patient with a severe traumatic loss of otoconia from both maculae utriculi and a persistent imbalance more than 9years. We think that the loss of otoconia from the utricular and probably also saccular macula induced a sudden reduction of her ability to sense gravity thus logically explaining her symptoms. We show the vestibular test results also supporting our hypothesis and we extrapolate this support to other forms of so far unexplained dizziness especially increasing imbalance with aging. We also discuss the normal c- and oVEMP indicating intact haircell function and supporting our hypothesis of isolated otoconial loss as the major cause for imbalance.

Temporal bone histopathology in MELAS syndrome.

ObjectivesDescribe the histopathology of the temporal bones in MELAS (myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes) syndrome. The syndrome results from a known point mutation in mitochondrial DNA.MethodsHistopathology analysis of a pair of temporal bones from the oldest surviving MELAS syndrome temporal bone donor. Histopathologic findings were correlated with known premortem clinical data.ResultsThe inner ears showed severe but incomplete atrophy of the stria vascularis for the length of the cochleae. In contrast, the organ of Corti and inner hair cells appeared intact with some loss of outer hair cells. Other than moderate loss at the basal turn, spiral ganglion cells numbers were normal. The vestibular neuroepithelium was mostly normal with the exception of moderate degeneration of the macula sacculi and partial collapse of the saccular wall on the right. The cerebral cortex had infarct‐like lesions with adjacent gliosis.ConclusionThis is an analysis of the oldest patient with MELAS syndrome to date, an addition to only two previously published patients. It supports the notion that hearing loss is a result of dysfunction of the stria vascularis and not loss of hair cells or neurons. Patterns of vestibular pathology are in agreement to in‐vivo measurements. These findings support auditory rehabilitation with cochlear implants and may be relevant to hearing loss due to other mitochondrial mutations.Level of evidence4

Transcriptomic Analyses of Inner Ear Sensory Epithelia in Zebrafish.

Analysis of gene expression has the potential to assist in the understanding of multiple cellular processes including proliferation, cell-fate specification, senesence, and activity in both healthy and disease states. Zebrafish model has been increasingly used to understand the process of hearing and the development of the vertebrate auditory system. Within the zebrafish inner ear, there are three otolith organs, each containing a sensory macula of hair cells. The saccular macula is primarily involved in hearing, the utricular macula is primarily involved in balance and the function of the lagenar macula is not completely understood. The goal of this study is to understand the transcriptional differences in the sensory macula associated with different otolith organs with the intention of understanding the genetic mechanisms responsible for the distinct role each organ plays in sensory perception. The sensory maculae of the saccule, utricle, and lagena were dissected out of adult Et(krt4:GFP)sqet4 zebrafish expressing green fluorescent protein in hair cells for transcriptional analysis. The total RNAs of the maculae were isolated and analyzed by RNA GeneChip microarray. Several of the differentially expressed genes are known to be involved in deafness, otolith development and balance. Gene expression among these otolith organs was very well conserved with less than 10% of genes showing differential expression. Data from this study will help to elucidate which genes are involved in hearing and balance. Furthermore, the findings of this study will assist in the development of the zebrafish model for human hearing and balance disorders. Anat Rec, 303:527-543, 2020. © 2019 American Association for Anatomy.

Peripheral Vestibular Organ Degeneration After Temporal Bone Fracture: A Human Otopathology Study.

Vestibular symptoms are a common sequela of temporal bone fractures (TBFs). The mechanisms of injury to the peripheral vestibular system following TBF, however, are not well described. Herein, we aimed to investigate the histopathology of the peripheral vestibular system in patients who sustained TBFs. Retrospective human specimen analysis. Specimens from the National Temporal Bone Pathology Registry with (cases) and without (controls) TBFs were evaluated. Specimens were analyzed by light microscopy for vestibular hair cell and/or dendritic degeneration, presence of endolymphatic hydrops, blockage of the endolymphatic duct, and number of Scarpa ganglion cells (ScGCs) in the superior and inferior vestibular nerves. Seven temporal bones (TBs) from five individuals with TBFs, and seven TBs from six age-matched individuals without a history of head injury met inclusion and exclusion criteria. All fractures involved the otic capsule. Severe degeneration of the cristae was identified in the semicircular canals in all TBF cases. The utricular and saccular maculae showed mild to severe degeneration in the TBF cases. Vestibular hydrops (n = 2 TBs) and blockage of the endolymphatic duct (n = 3 TBs) were also present in the TBF cases. There was a decrease of 52.6% in the mean total ScGC count in the TBF cases (n = 3 TBs) compared to age-matched controls (n = 7 TBs, P = .015). There was a mean loss of 53% of the ScGCs in the superior vestibular nerve and a mean loss of 52.3% of the ScGCs in the inferior vestibular nerve compared to age-matched controls (P = .033 and P = .021, respectively). In a cohort of patients with TBFs, there were distinct peripheral vestibular changes including reduction of ScGCs. NA Laryngoscope, 130:752-760, 2020.

Otolithic Receptor Mechanisms for Vestibular-Evoked Myogenic Potentials: A Review.

Air-conducted sound and bone-conduced vibration activate otolithic receptors and afferent neurons in both the utricular and saccular maculae, and trigger small electromyographic (EMG) responses [called vestibular-evoked myogenic potentials (VEMPs)] in various muscle groups throughout the body. The use of these VEMPs for clinical assessment of human otolithic function is built on the following logical steps: (1) that high-frequency sound and vibration at clinically effective stimulus levels activate otolithic receptors and afferents, rather than semicircular canal afferents, (2) that there is differential anatomical projection of otolith afferents to eye muscles and neck muscles, and (3) that isolated stimulation of the utricular macula induces short latency responses in eye muscles, and that isolated stimulation of the saccular macula induces short latency responses in neck motoneurons. Evidence supports these logical steps, and so VEMPs are increasingly being used for clinical assessment of otolith function, even differential evaluation of utricular and saccular function. The proposal, originally put forward by Curthoys in 2010, is now accepted: that the ocular vestibular-evoked myogenic potential reflects predominantly contralateral utricular function and the cervical vestibular-evoked myogenic potential reflects predominantly ipsilateral saccular function. So VEMPs can provide differential tests of utricular and saccular function, not because of stimulus selectivity for either of the two maculae, but by measuring responses which are predominantly determined by the differential neural projection of utricular as opposed to saccular neural information to various muscle groups. The major question which this review addresses is how the otolithic sensory system, with such a high density otoconial layer, can be activated by individual cycles of sound and vibration and show such tight locking of the timing of action potentials of single primary otolithic afferents to a particular phase angle of the stimulus cycle even at frequencies far above 1,000 Hz. The new explanation is that it is due to the otoliths acting as seismometers at high frequencies and accelerometers at low frequencies. VEMPs are an otolith-dominated response, but in a particular clinical condition, semicircular canal dehiscence, semicircular canal receptors are also activated by sound and vibration, and act to enhance the otolith-dominated VEMP responses.

In vivo recording of the vestibular microphonic in mammals

BackgroundThe Vestibular Microphonic (VM) has only featured in a handful of publications, mostly involving non-mammalian and ex vivo models. The VM is the extracellular analogue of the vestibular hair cell receptor current, and offers a tool to monitor vestibular hair cell activity in vivo. ObjectiveTo characterise features of the VM measured in vivo in guinea pigs, using a relatively simple experimental setup. MethodsThe VM, evoked by bone-conducted vibration (BCV), was recorded from the basal surface of either the utricular or saccular macula after surgical removal of the cochlea, in 27 guinea pigs. ResultsThe VM remained after vestibular nerve blockade, but was abolished following end-organ destruction or death. The VM reversed polarity as the recording electrode tracked across the utricular or saccular macula surface, or through the utricular macula. The VM could be evoked by BCV stimuli of frequencies between 100 Hz and 5 kHz, and was largest to vibrations between 600 Hz and 800 Hz. Experimental manipulations demonstrated a reduction in the VM amplitude with maculae displacement, or rupture of the utricular membrane. ConclusionsResults mirror those obtained in previous ex vivo studies, and further demonstrate that vestibular hair cells are sensitive to vibrations of several kilohertz. Changes in the VM with maculae displacement or rupture suggest utricular hydrops may alter vestibular hair cell sensitivity due to either mechanical or ionic changes.

Ontogenetic development of the inner ear saccule and utricle in the Lusitanian toadfish: Potential implications for auditory sensitivity

Studies addressing structure-function relationships of the fish auditory system during development are sparse compared to other taxa. The Batrachoididae has become an important group to investigate mechanisms of auditory plasticity and evolution of auditory-vocal systems. A recent study reported ontogenetic improvements in the inner ear saccule sensitivity of the Lusitanian toadfish, Halobatrachus didactylus, but whether this results from changes in the sensory morphology remains unknown. We investigated how the macula and organization of auditory receptors in the saccule and utricle change during growth in this species. Inner ear sensory epithelia were removed from the end organs of previously PFA-fixed specimens, from non-vocal posthatch fry (<1.4 cm, standard length) to adults (>23 cm). Epithelia were phalloidin-stained and analysed for area, shape, number and orientation patterns of hair cells (HC), and number and size of saccular supporting cells (SC).Saccular macula area expanded 41x in total, and significantly more (relative to body length) among vocal juveniles (2.3–2.9 cm). Saccular HC number increased 25x but HC density decreased, suggesting that HC addition is slower relative to epithelial growth. While SC density decreased, SC apical area increased, contributing to the epithelial expansion.The utricule revealed increased HC density (striolar region) and less epithelial expansion (5x) with growth, contrasting with the saccule that may have a different developmental pattern due to its larger size and main auditory functions. Both macula shape and HC orientation patterns were already established in the posthatch fry and retained throughout growth in both end organs.We suggest that previously reported ontogenetic improvements in saccular sensitivity might be associated with changes in HC number (not density), size and/or molecular mechanisms controlling HC sensitivity. This is one of the first studies investigating the ontogenetic development of the saccule and utricle in a vocal fish and how it potentially relates to auditory enhancement for acoustic communication.