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The geniculate ganglion (GG) contains visceral and somatic sensory neurons of the facial nerve. In this study, the number and cell size of sensory neurons in the human GG were investigated. The estimated number of GG neurons ranged from 1,580 to 2,561 (mean ± SD = 1,960 ± 364.6). The cell size of GG neurons ranged from 393.0 to 2,485.4 μm2 (mean ± SD = 1,067.4 ± 99.5 μm2). Sensory neurons in the GG were significantly smaller in size than those in the dorsal root (range = 326.6-5343.4 μm2, mean ± SD = 1,683.2 ± 203.8 μm2) or trigeminal ganglia (range = 349.6-4,889.28 μm2, mean ± SD = 1,529.0 ± 198.48 μm2). Sensory neurons had similar cell body sizes in the GG and nodose ganglion (range = 357.2-3,488.33 μm2, mean ± SD = 1,160.4 ± 156.61 μm2). These findings suggest that viscerosensory neurons have smaller cell bodies than somatosensory neurons. In addition, immunohistochemistry for several neurochemical substances was performed on the human GG. In the ganglion, sensory neurons were mostly immunoreactive for secreted protein, acidic and rich in cysteine-like 1 (94.3%). One third of GG neurons showed vesicular glutamate transporter 2 immunoreactivity (31.3%). Only 7.3% of GG neurons were immunoreactive for transient receptor potential cation channel subfamily V member 1. Sensory neurons in the human GG may respond to gustatory, nociceptive, and/or mechanoreceptive stimuli from tongues, soft palates, and external auditory canals.

Objectives CANVAS is an acronym for cerebellar ataxia, neuropathy and vestibular areflexia syndrome. Limited autopsy data has suggested that CANVAS is caused by a focal dorsal root ganglionopathy that damages Scarpa's (vestibular) ganglion, but spares the Spiral (hearing) ganglion. If the vestibular areflexia of CANVAS is in fact due to ganglionopathy, then there should be global reduction of all vestibular responses. Materials and methods With this hypothesis in mind, a retrospective review of 5 subjects who met the clinical criteria for CANVAS was performed. Recent advances in vestibular testing have made it possible to quantify responses from all 5 vestibular end organs in the inner ear. Results of the Video head impulse test (VHIT), video oculography, caloric test and vestibular evoked myogenic potential (VEMP) were examined to determine if all 5 end organs are nonfunctional in CANVAS. Results Severe reduction of function of the six semicircular canals and ocular VEMPs were observed. Only the cervical VEMPs were present and reproducible, consistent with either partial sparing of the inferior vestibular ganglia, specific embryologic resistance of the saccule to the degeneration or a mechanism for cervical VEMPs that does not require an intact vestibular ganglion. Conclusion Our results suggest that Scarpa´s ganglia dysfunction could be the mechanism for loss of semicircular canal and utricular function in CANVAS patients, but the preservation of the cervical VEMP response is unexplained.

The inner ear is a complex organ comprised of various specialized sensory organs for detecting sound and head movements. The timing of specification for these sensory organs, however, is not clear. Previous fate mapping results of the inner ear indicate that vestibular and auditory ganglia and two of the vestibular sensory organs, the utricular macula (UM) and saccular macula (SM), are lineage related. Based on the medial-lateral relationship where respective auditory and vestibular neuroblasts exit from the otic epithelium and the subsequent formation of the medial SM and lateral UM in these regions, we hypothesized that specification of the two lateral structures, the vestibular ganglion and the UM are coupled and likewise for the two medial structures, the auditory ganglion and the SM. We tested this hypothesis by surgically inverting the primary axes of the otic cup in ovo and investigating the fate of the vestibular neurogenic region, which had been spotted with a lipophilic dye. Our results showed that the laterally-positioned, dye-associated, vestibular ganglion and UM were largely normal in transplanted ears, whereas both auditory ganglion and SM showed abnormalities suggesting the lateral but not the medial-derived structures were mostly specified at the time of transplantation. Both of these results are consistent with a temporal coupling between neuronal and macular fate specifications.

In the standard model for the development of climbing and mossy fiber afferent pathways to the cerebellum, the ingrowing axons target the embryonic Purkinje cell somata (around embryonic ages (E13-E16 in mice). In this report, we describe a novel earlier stage in afferent development. Immunostaining for a neurofilament-associated antigen (NAA) reveals the early axon distributions with remarkable clarity. Using a combination of DiI axon tract tracing, analysis of neurogenin1 null mice, which do not develop trigeminal ganglia, and mouse embryos maintained in vitro, we show that the first axons to innervate the cerebellar primordium as early as E9 arise from the trigeminal ganglion. Therefore, early trigeminal axons are in situ before the Purkinje cells are born. Double immunostaining for NAA and markers of the different domains in the cerebellar primordium reveal that afferents first target the nuclear transitory zone (E9-E10), and only later (E10-E11) are the axons, either collaterals from the trigeminal ganglion or a new afferent source (e.g., vestibular ganglia), seen in the Purkinje cell plate. The finding that the earliest axons to the cerebellum derive from the trigeminal ganglion and enter the cerebellar primordium before the Purkinje cells are born, where they seem to target the cerebellar nuclei, reveals a novel stage in the development of the cerebellar afferents.

Preparation of the temporal bone for light microscopy is an important step in histological studies of the inner ear. Due to the complexity of structures of the inner ear, it is difficult to measure or compare structures of interest without a commonly accepted standardized measure of temporal bone sections. Therefore, standardization of temporal bone sections is very important for histological assessment of sensory hair cells and peripheral ganglion neurons in the cochlear and vestibular systems. The standardized temporal bone sectioning is oriented to a plane parallel to the outer and internal auditory canals. Sections are collected from the epitympanum to the hypotympanum to reveal layers in the order of the crista ampullaris of the superior and lateral semicircular canals, macula utriculi and macula sacculi, superior vestibular ganglion neurons, macula of saccule and inferior vestibular ganglion neurons, cochlear modiolus, endolymphatic duct and endolymphatic sac, and finally the crista ampullaris of the posterior semicircular canal. Moreover, technical details of preparing for temporal bone sectioning including fixation, decalcification, whole temporal bone staining, embedding penetration, and embedding orientation are also discussed.

The use of viral vectors for inner ear gene therapy is receiving increased attention for treatment of genetic hearing disorders. Most animal studies to date have injected viral suspensions into neonatal ears, via the round window membrane. Achieving transduction of hair cells, or sensory neurons, throughout the cochlea has proven difficult, and no studies have been able to efficiently transduce sensory cells in adult ears while maintaining normal cochlear function. Here, we show, for the first time, successful transduction of all inner hair cells and the majority of outer hair cells in an adult cochlea via virus injection into the posterior semicircular canal. We used a “designer” AAV, AAV2/Anc80L65, in which the main capsid proteins approximate the ancestral sequence state of AAV1, 2, 8, and 9. Our injections also transduced ~10% of spiral ganglion cells and a much larger fraction of their satellite cells. In the vestibular sensory epithelia, the virus transduced large numbers of hair cells and virtually all the supporting cells, along with close to half of the vestibular ganglion cells. We conclude that this viral vector and this delivery route hold great promise for gene therapy applications in both cochlear and vestibular sense organs.

The vestibular system of the inner ear is designed to detect linear acceleration (maculae) and angular acceleration (cristae). Both organs contain hair cells with stereocilia (“hairs”) that detect deflection toward or away from a polarizing kinocilium. Hair cells respond to these deflections by an increase or decrease in transmitter release, respectively, from a constant baseline release. This transmitter generates action potentials in the vestibular nerve fibers that are transmitted to the vestibular complex in the dorsolateral brain stem and to the vestibulocerebellum. The vestibular complex projects to: the spinal cord to change muscle tone in response to vestibular stimuli; the extraocular nuclei to stabilize the eyes with head movement (vestibulo-ocular reflex); the reticular formation to produce autonomic changes in response to vestibular stimulation; the thalamus for relay to the cortex for perception of movement; and interconnects with the vestibulocerebellum to allow for adjustment of vestibular responses due to changing conditions.

To gain insights into the ototoxic effects of aminoglycoside antibiotics (AmAn) and delayed peripheral ganglion neuron death in the inner ear, experimental animal models were widely used with several different approaches including AmAn systemic injections, combination treatment of AmAn and diuretics, or local application of AmAn. In these approaches, systemic AmAn treatment alone usually causes incomplete damage to hair cells in the inner ear. Co-administration of diuretic and AmAn can completely destroy the cochlear hair cells, but it is impossible to damage the vestibular system. Only the approach of AmAn local application can selectively eliminate most sensory hair cells in the inner ear. Therefore, AmAn local application is more suitable for studies for complete hair cell destructions in cochlear and vestibular system and the following delayed peripheral ganglion neuron death. In current studies, guinea pigs were unilaterally treated with a high concentration of gentamicin (GM, 40 mg/ml) through the tympanic membrane into the middle ear cavity. Auditory functions and vestibular functions were measured before and after GM treatment. The loss of hair cells and delayed degeneration of ganglion neurons in both cochlear and vestibular system were quantified 30 days or 60 days after treatment. The results showed that both auditory and vestibular functions were completely abolished after GM treatment. The sensory hair cells were totally missing in the cochlea, and severely destroyed in vestibular end-organs. The delayed spiral ganglion neuron death 60 days after the deafening procedure was over 50%. However, no obvious pathological changes were observed in vestibular ganglion neurons 60 days post-treatment. These results indicated that a high concentration of gentamycin delivered to the middle ear cavity can destroy most sensory hair cells in the inner ear that subsequently causes the delayed spiral ganglion neuron degeneration. This model might be useful for studies of hair cell regenerations, delayed degeneration of peripheral auditory neurons, and/or vestibular compensation. In addition, a potential problem of ABR recording for unilateral deafness and issues about vestibular compensation are also discussed.

The aim of this study was to elucidate the mechanism of isolated vascular vertigo by determining selective and relative ischemic vulnerability of the vestibular structures using a global hypoperfusion model in rats. Sprague-Dawley male rats weighing 330-350 g were subjected to transient global ischemia of the brain using a 4-vessel-occlusion (4VO) model. After permanent occlusion of both vertebral arteries (VA) using electrocauterization, both common carotid arteries (CCAs) were occluded for 5-20 min with ligation. One hour after reperfusion of the CCAs, the animals were sacrificed and subjected to c-Fos staining of the entire cerebellum, brainstem, and vestibular ganglion. The rats in the sham group received the same surgical procedures except the vessel ligation. With 4VO for 5-15 min, both the sham and experimental groups showed a weak and scarce c-Fos expression in the medial vestibular nucleus (MVN), neuron Y, and cochlear nucleus. After 4VO for 20 min, only the MVN began to show a significant difference in the number of c-Fos positive neurons between the experimental and sham groups (33.7±17.7 vs.7.1±5.1, Wilcoxon rank test, p=0.005). With 4VO for up to 20 min, c-Fos positive neurons were not found in other areas of the brainstem and cerebellum, including the superior, lateral, and spinal vestibular nuclei, the vestibular ganglion, the cerebellar cortex, and the deep cerebellar nuclei. The vestibular structures appear to be vulnerable to ischemia more than any other structures in the brainstem and cerebellum. Of the vestibular structures, the MVN is most vulnerable to ischemic insults in rats. These findings are consistent with the common findings of vertigo as an initial and isolated symptom of posterior circulation ischemia in human.

The methionine sulfoxide reductase (Msr) family of proteins is a class of repair enzymes that reduce methionine-S (MsrA) or methionine-R (MsrB) sulfoxide to methionine. Recent studies have reported that mutations in the MSRB3 gene cause autosomal recessive hearing loss in humans, and in mice MsrB3 deficiency leads to profound hearing loss due to hair cell apoptosis and stereocilia degeneration. However, apart from MsrB3, studies on Msr proteins in the inner ear have not yet been reported. In this study, we identified and characterized Msr expression in the cochlea and vestibule. First, we confirmed RNA expression levels of Msr family members in the cochlea and vestibule using reverse transcription PCR and detected Msr family members in both tissues. We also conducted immunohistochemical staining to localize Msr family members within the cochlea and vestibule. In the cochlea, MsrA was detected in supporting cells, spiral ligament, spiral limbus, Reissner's membrane and the spiral ganglion. MsrB1 was specifically expressed in hair cells and the spiral ganglion. MsrB2 was noted in the spiral ganglion, tectorial membrane and stria vascularis. In the vestibule, MsrA and MsrB1 were detected in hair cells and the vestibular ganglion, while MsrB2 was restricted to the vestibular ganglion. In this study, we identified distinct distributions of Msr family members in the organ of Corti and hypothesized that MsrA, MsrB1 and MsrB2 protect proteins in the organ of Corti from oxidative stress.

The morphology of the trigeminal ganglion in human fetus was investigated by means of the tract-tracing method using the lipophilic dye DiI-C18-(3) (1,1'-double octadecane 3,3,3'3'-tetramethyl indole carbonyl cyanine-perchlorate), hematoxylin-eosin (HE) stain, and three-dimensional computer reconstruction models. The trigeminal ganglion was flat in the dorsoventral direction, and DiI staining revealed that the trigeminal ganglion cells were somatotopically distributed in the ganglion in a way that reflected the mediolateral order of the three branches. Ganglion cells of the ophthalmic nerve were distributed in the anteromedial part of the trigeminal ganglion, those of the mandibular nerve were in the posterolateral part, and those of the maxillary nerve were localized in the intermediate part. DiI labeled both ganglion cells and nerve fibers in the trigeminal ganglion; the ganglion cells varied in size and appeared as round- or oval-shaped, the neurites connected the cell soma, and some bipolar neurons were also observed. The number of embryonic trigeminal ganglion cells did not significantly change with gestational age, but the cell diameter, area, and perimeter significantly increased. The motor root leaves the pons, runs along the sensory root, passes the ventral surface of the ganglion, and finally runs together with the mandibular nerve. The findings reported here elucidate the morphology, development, and somatotopic organization of the trigeminal ganglion and reveal the trigeminal nerve motor root pathway along the trigeminal ganglion and mandibular nerve in the human fetus.

Vestibular ganglion cells, which convey sense of motion from vestibular hair cells to the brainstem, are known to degenerate with aging and after vestibular neuritis. Thus, regeneration of vestibular ganglion cells is important to aid in the recovery of balance for associated disorders.The present study derived hNSCs from induced pluripotent stem cells (iPSCs) and transplanted these cells into mouse utricle tissues. After a 7-day co-culture period, histological and electrophysiological examinations of transplanted hNSCs were performed.Injected hNSC-derived cells produced elongated axon-like structures within the utricle tissue that made contact with vestibular hair cells. A proportion of hNSC-derived cells showed spontaneous firing activities, similar to those observed in cultured mouse vestibular ganglion cells. However, hNSC-derived cells around the mouse utricle persisted as immature neurons or occasionally differentiated into putative astrocytes. Moreover, electrophysiological examination showed hNSC-derived cells around utricles did not exhibit any obvious spontaneous firing activities.Injected human neural stem cells (hNSCs) showed signs of morphological maturation including reconnection to denervated hair cells and partial physiological maturation, suggesting hNSC-derived cells possibly differentiated into neurons.

This study aimed to investigate the genetic causes of vestibular dysfunction. We used vestibular sensory-evoked potentials (VsEPs) to characterize the vestibular function of 35 inbred mouse strains selected from the Hybrid Mouse Diversity Panel and demonstrated strain-dependent phenotypic variation in vestibular function. Using these phenotypic data, we performed the first genome-wide association study controlling for population structure that has revealed two highly suggestive loci, one of which lies within a haplotype block containing five genes (Stard6, 4930503L19Rik, Poli, Mbd2, Dcc) on Chr. 18 (peak SNP rs29632020), one gene, deleted in colorectal carcinoma (Dcc) has a well-established role in nervous system development. An in-depth analysis of Dcc-deficient mice demonstrated elevation in mean VsEP threshold for Dcc +/− mice (−11.86 dB) compared to wild-type (−9.68 dB) littermates. Synaptic ribbon studies revealed Dcc −/− (P0) and Dcc +/− (6-week-old) mice showed lower density of the presynaptic marker (CtBP2) as compared to wild-type controls. Vestibular ganglion cell counts of Dcc −/− (P0) was lower than controls. Whole-mount preparations showed abnormal innervation of the utricle, saccule, and crista ampullaris at E14.5, E16.5, and E18.5. Postnatal studies were limited by the perinatal lethality in Dcc −/− mice. Expression analyses using in situ hybridization and immunohistochemistry showed Dcc expression in the mouse vestibular ganglion (E15.5), and utricle and crista ampullaris (6-week-old), respectively. In summary, we report the first GWAS for vestibular functional variation in inbred mice and provide evidence for the role of Dcc in the normal innervation of the peripheral vestibular system.

The study was carried out on three 4-month old female pigs. All the animals were deeply anesthetized and transcardially perfused with 4% buffered paraformaldehyde (pH 7.4). Vestibular ganglia (VG) were collected and processed for double-labelling immunofluorescence method. The preparations were examined under the Zeiss LSM 710 confocal microscope equipped with adequate filter blocks. Neurons forming VG were round or oval in shape with a round nucleus in the center. The majority of them (58%) were medium (M) (31-50 μm in diameter) while 28 % and 14% were small (S) (up to 30 μm in diameter) or large (L) (above 50 μm in diameter) in size, respectively. Double-labeling immunofluorescence revealed that VG neurons stained for CGRP (approx. 81%; among them 70.5%, 26.2% and 3.3% were M, S and L in size, respectively), VACHT (57%; 63% M, 24% S, 13% L), Met-Enk (25%; 60% M, 12% S, 28% L), VIP (20%; 88% M, 6% S, L), NPY (15%; 67% M, 20% S, 13% L), GAL (15%; 74% M, 21% S, 5% L), SP (12%; 69% M, 25% S, 6% L) and NOS-positive (12%; 50% S, 50% M). The most abundant populations of intraganglionic nerve fibers were those which stained for CGRP or Met-Enk, whereas only single SP- or NOS-positive nerve terminals were observed.

In cases of acquired sensorineural hearing loss, death of cochlear neurons is thought to arise largely as a result of sensory-cell loss. However, recent studies of acoustic overexposure report massive degeneration of the cochlear nerve despite complete hair cell survival (Kujawa and Liberman, J Neurosci 29:14077-14085, 2009). To assess the primary loss of spiral ganglion cells (SGCs) in human ears, neuronal counts were performed in 100 temporal bones from 100 individuals, aged newborn to 100 years, selected to include only cases with a normal population of inner and outer hair cells. Ganglion cell counts declined at a mean rate of 100 cells per year of life. There were no significant gender or inter-aural differences, and a slight increase in degeneration in the basal turn re upper turns was not statistically significant. The age-related decline in SGCs was significantly less than that in prior studies that included ears with hair cell loss (Otte et al., Laryngoscope 88:1231-1246, 1978), but significantly more than for analogous data on vestibular ganglion cells in cases without vestibular hair cell loss (Velazquez-Villasenor et al., Ann Otol Rhinol Laryngol Suppl 181:14-19, 2000). The age-related decline in SGC counts may contribute to the well-known decline in hearing-in-noise performance, and the data will help in interpretation of histopathological findings from temporal bones with known otologic disease.

INTRODUCTION In vestibular schwannoma (VS) surgery, the arachnoidal duplication, based on an epiarachnoidal origin of the tumor, is reputedly induced by medial growth of tumor and helpful in atraumatic dissection. This study was intended to verify the epiarachnoidal origin of VS. MATERIALS AND METHODS We studied 49 human temporal bones (TBs) specimens. Twenty-two TBs from 18 patients with VS were selected. An additional series of 27 TBs without any tumor within the internal auditory meatus were also included. We identified the location of the meninges and the position of the transition zone inside the meatus and described the lateral extension of the subarachnoid spaces. RESULTS In VS specimens, psammoma bodies were seen at the fundus along the arachnoidal layer. No connective tissue or protrusion of a psammoma body was observed between the nerves and the VS. High magnification failed to demonstrate any meningeal cleavage plane between the facial or cochlear nerve and the tumor. The subarachnoid space was visible within the internal auditory meatus and extended from the porus to the fundus. In every case, the transition zone, the vestibular ganglion, or the VS was located in the subarachnoid fluid space. CONCLUSION We were not able to identify any layer between tumor and the intrameatal contents and did not observe any conjunctive-tissue capsule surrounding the intrameatal VS, as an epiarachnoidal tumor origin would suggest. These observations are in contradiction with the descriptions concerning the epiarachnoidal origin of VS.

The concept that reactivation of latent neurotropic viruses (i.e. Herpesviridae group) in the vestibular ganglion is responsible for recurrent vestibulopathies is presented. A similar histopathologic degeneration of vestibular ganglion cells in vestibular neuronitis (VN), Ménière’s disease and benign paroxysmal positional vertigo is presented to support this concept. The clinical response (relief of vertigo) to the administration of antiviral medication in these syndromes provides practical evidence of a viral neuropathy in patients with recurrent vertigo. Relief of vertigo after this treatment was 90% in VN, Ménière’s disease and VN. The relief of positional vertigo (benign paroxysmal positional vertigo) was 66%.

Introduction Dizziness is a common symptom in patients with vestibulo-cochlear schwannoma (VS), and several recent studies have identified this symptom as the single most important concerning the quality of life. Clinical and histological observations regarding hearing loss have suggested that this may be caused by both cochlear and retrocochlear mechanisms. Multiple mechanisms may also be at play in the case of dizziness, which may broaden perspectives of therapeutic approach. This study presents a systematic and detailed assessment of vestibular histopathology in temporal bones from patients with VS. Methods Retrospective analysis of vestibular system histopathology in temporal bones from 17 patients with unilateral VS. The material was obtained from The Copenhagen Temporal Bone Collection. Results Vestibular schwannomas were associated with atrophy of the vestibular ganglion, loss of fiber density of the peripheral vestibular nerve branches, and atrophy of the neuroepithelium of the vestibular end organs. In cases with small tumors, peripheral disease occurred only in the tissue structures innervated by the specific nerve from which the tumor originated. Conclusion Vestibular schwannomas are associated with distinctive disease of the peripheral vestibular tissue structures, suggesting anterograde degeneration and that dizziness in these patients may be caused by deficient peripheral vestibular nerve fibers, neurons, and end organs. In smaller tumors, a highly localized disease occurs, which opens perspectives of differentiated clinical assessment and subsequent, targeted therapy.

The auditory-vestibular ganglion (AVG) is formed by the division of otic placode-derived neuroblasts, which then differentiate into auditory and vestibular afferent neurons. The developmental mechanisms that regulate neuronal cell fate determination, axonal pathfinding and innervation of otic neurons are poorly understood. The present study characterized the expression of myosin VIIA, along with the neuronal markers, Islet1, NeuroD1 and TuJ1, in the developing avian ear, during Hamburger–Hamilton (HH) stages 16–40. At early stages, when neuroblasts are delaminating from the otic epithelium, myosin VIIA expression was not observed. Myosin VIIA was initially detected in a subset of neurons during the early phase of neuronal differentiation (HH stage 20). As the AVG segregates into the auditory and vestibular portions, myosin VIIA was restricted to a subset of vestibular neurons, but was not present in auditory neurons. Myosin VIIA expression in the vestibular ganglion was maintained through HH stage 33 and was downregulated by stage 36. Myosin VIIA was also observed in the migrating processes of vestibular afferents as they begin to innervate the otic epithelium HH stage 22/23. Notably, afferents targeting hair cells of the cristae were positive for myosin VIIA while afferents targeting the utricular and saccular maculae were negative (HH stage 26–28). Although previous studies have reported that myosin VIIA is restricted to sensory hair cells, our data shows that myosin VIIA is also expressed in neurons of the developing chick ear. Our study suggests a possible role for myosin VIIA in axonal migration/pathfinding and/or innervation of vestibular afferents. In addition, myosin VIIA could be used as an early marker for vestibular neurons during the development of the avian AVG.

Hizli, Omer/0000-0001-6822-2679; Adams, Meredith/0000-0002-7962-3475 WOS: 000367745700022 PubMed: 26307578 Objective Dizziness associated with vestibular schwannoma is usually ascribed to retrolabyrinthine mechanisms. The goal of this study was to determine if quantitative peripheral vestibular (labyrinthine) otopathology was present in a series of patients with vestibular schwannoma. Study Design Comparative human temporal bone study. Setting Otopathology laboratory. Subjects and Methods Temporal bones from 12 subjects with unilateral sporadic vestibular schwannoma were included. Based on differential interference contrast microscopy, type I and II vestibular hair cell counts were performed on each vestibular sense organ with minimal autolysis in which the neuroepithelium was oriented perpendicular to the plane of section. Hair cell densities (cells per 0.01-mm(2) surface area) and the presence of endolymphatic hydrops and precipitate within the endolymph or perilymph were compared between the tumor ears and the contralateral (control) ears. Results Compared with the contralateral ears, vestibular schwannoma ears had significantly more endolymphatic hydrops (P = .049) and precipitate in the endolymph and perilymph (P = .005), lower densities of type I and II vestibular hair cells in the lateral canal cristae (mean differences, respectively: 25.2 [P = .001] and 10.8 [P < .001]) and utricle (mean differences, respectively: 26.8 and 10.4 [P < .001]), and lower densities of type I hair cells and the same density of type II hair cells in the saccule (mean differences, respectively: 26.5 [P < .001] and 0.9 [P = .46]). Conclusion Peripheral vestibular otopathology, manifested as reductions of vestibular hair cell densities, was identified in ears with vestibular schwannoma. Labyrinthine as well as retrolabyrinthine pathology may contribute to tumor-related vestibular dysfunction. National Institutes of Health / National Institute on Deafness and Other Communication DisordersUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Deafness & Other Communication Disorders (NIDCD) [U24 DC011968-01]; International Hearing Foundation; Starkey Foundation; 5M Lions International; Scientific and Technological Research Council of TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) This work was funded by the National Institutes of Health / National Institute on Deafness and Other Communication Disorders (U24 DC011968-01), the International Hearing Foundation, the Starkey Foundation, and 5M Lions International. Omer Hizli and Serdar Kaya also received the Scientific and Technological Research Council of Turkey Scholarship.

Intrinsic differences in neurons of the vestibular ganglia result in the increased likelihood of superior vestibular ganglion involvement in vestibular neuritis.Vestibular neuritis is hypothesized to result from herpes simplex type I (HSV1) infection or reactivation in vestibular ganglia. Involvement of the inferior vestibular ganglion is extremely rare in patients with vestibular neuritis.Primary cultures of rat superior and inferior vestibular ganglion neurons (VGNs) were cultivated separately. Neurons were lytically and latently infected with HSV1 with a US11-green fluorescent protein (GFP) chimera. Percentage lytic infection and baseline reactivation was assessed by microscopy for GFP fluorescence. Trichostatin-A (TSA) was used to stimulate HSV1 reactivation. Virion production was assessed by viral titers. Relative numbers of latency-associated (LAT) transcripts were determined by real-time reverse-transcription polymerase chain reaction (real-time RT-PCR).Lytic infection rates were equivalent between the two ganglia (p0.05). Lytic infections yielded similar amounts of plaque-forming units (p0.05). Relative amounts of LAT transcripts did not differ between latently infected superior and inferior VGNs. Latently infected cultures showed no differences in rates of baseline and TSA-induced HSV1 reactivation (p0.05). Production of virions was not significantly different between reactivated, latently infected superior versus inferior VGNs (p = 0.45).Differences in prevalence of superior and inferior vestibular neuritis do not result from intrinsic differences in HSV1 infection or virion production of these neurons. Other factors, such as the length and width of the bony canal containing the ganglia and nerves, account for the greater involvement of the superior vestibular ganglion in vestibular neuritis.

The recording of vestibular evoked myogenic potentials is a relatively new neuro-otologic method which gives specific information about the function of the sacculus and the inferior vestibular nerve on each side separately. The main indications for this method are vestibular schwannoma and fistula of the labyrinth, involvement of the sacculus or the inferior vestibular nerve in Meniere's disease and vestibular neuritis, vertigo of unknown etiology, and forensic questions.

The acquisition of ion channels is critical to the formation of neuronal pathways in the peripheral and central nervous systems. This study describes the different types of inward currents (I i ) recorded from the soma of isolated cochleovestibular ganglion (CVG) cells of the embryonic chicken, Gallus gallus. Cells were isolated for whole-cell tight-seal recording from embryonic day (ED) 3, an age when the CVG is a cell cluster, to ED 9, an age when the cochlear and vestibular ganglia (CG, VG) are distinct structures. Results show Na + and Ca + currents (I Na and I Ca ) are acquired by ED 3, although / Na dominates with greater density levels that peak by ED 6-7 in VG neurons. In the CG, / Na acquisition is slower, reaching peak values by ED 8-9. Isolation of I Ca , using Ba 2+ as the charge carrier, showed both transient (I BaT )- and sustained (I BaL )-type currents on ED 3. Unlike I Na , I Ba density varied with age and ganglion. Total I Ba increased steadily, showing a decline only in CG cells on ED 8-9 as a result of a decrease in I BaT . I BaL density increased over time, reaching a maximum on ED 6-7 in VG cells, followed by a decline on ED 8-9. In comparison, I BaL in CG neurons, did not increase significantly beyond mean values measured on ED 5. The early onset of these currents and the variations in Ca 2+ channel expression between the ganglia suggests that intracellular signals relevant to phenotypic differentiation begin within these early time frames.

To delineate the vestibular afferent innervation in the vestibular efferent nucleus in the brainstem, neurobiotin or biotinylated dextran amine was injected into the superior Scarpa's ganglion of Sprague-Dawley rats. The locations of vestibular efferent neurons in the brainstem were identified by neutral red or choline acetyltransferase staining. Of the three pairs of vestibular efferent nuclei, labeled fibers and bouton-like endings were found only within the dorsolateral vestibular efferent nucleus on the ipsilateral side. Labeled afferent terminals with bouton-like varicosities were observed in the vicinity of cell bodies or dendrites of these efferent neurons. Our findings suggest that vestibular primary afferents may exert direct influence on vestibular efferent neurons, constituting an ipsilateral close-loop arrangement in the central vestibular system.

Using intracellular staining with horseradish peroxidase (HRP), Sato et al. (1989) demonstrated the course and termination in the vestibular nuclei of electrophysiologically identified single axons originating from the three semicircular canals. All semicircular canal-activated afferents terminated on all vestibular nuclei. The morphology of physiologically identified otolith-activated afferents (Imagawa et al. 1995, 1998) and 2nd order vestibular neurons (Meng et al. 2002) was investigated by similar methodology with HRP. The ascending branches of otolith axons give off collaterals with boutons in the caudal part of the superior nucleus. The descending branches coursed caudally through the lateral part of the descending nucleus, and gave off collaterals with boutons in the lateral, descending and medial vestibular nuclei. In summary, our data now complete the catalogue of the morphology of individual primary neurons innervating vestibular end organs, i.e. the three canals and the two otolith orngas. As a whole, canal and otolith afferents basically project to the same vestibular nuclei, although there are noticeable quantitative differences. Otolith projections to areas outside the vestibu-lar nuclei where ipsilateral abducens nucleus and reticular formation are present are quite different (Uchino et al. 1994, 1996).The morphology of vestibular neurons was studied by similar methodology with HRP (See Wilson and Melvill Jones 1979). The otolith-activated 2nd order vestibular neurons were pyramidal, elongated and ovoidal in shape. Most of the labeled cells were medium to large. There was no apparent correlation between morphology and the different types of otolith- and canal-activated vestibular neurons. Thus, it seems likely that the functional type of vestibular neurons cannot be presumed on the basis of their morphology alone.

Unilateral peripheral vestibular lesions are characterized by rapid recovery from the static symptoms, called vestibular compensation, a process likely involving brain plasticity. The hatchling chick offers a promising model for studies of this process. Ganglionectomy is performed, since it provides a reproducible lesion. Here, we describe a surgical approach for vestibular ganglionectomy and the identification of the otolith nerves, using drawings and digital images of the surgical field to assist in visualizing and accessing this small, complex, and highly vascular region of the inner ear. A retroauricular approach was used in 4-8-day-old hatchling chicks. Broad access and easy identification of the otolith nerves were achieved by cauterizing the caudal auricular artery and vein in the exoccipital bone and excising the surrounding exoccipital and squamosal bones. The vestibular ganglion was accessed by removing the bony medial wall of the vestibule. Dura mater covering the ganglion was opened, the primary vestibular fibers were cut at the lateral brain surface, and the anterior and posterior parts of the vestibular ganglion were extirpated. At 24 h after surgery, the survival rate was 87% and complete ganglionectomy was achieved in 85% of operated animals.

The function of the zinc finger transcription factor GATA3 was studied in a newly established, conditionally immortal cell line derived to represent auditory sensory neuroblasts migrating from the mouse otic vesicle at embryonic day E10.5. The cell line, US/VOT-33, expressed GATA3, the bHLH transcription factor NeuroD and the POU-domain transcription factor Brn3a, as do auditory neuroblasts in vivo. When GATA3 was knocked down reversibly with antisense oligonucleotides, NeuroD was reversibly down-regulated. Auditory and vestibular neurons form from neuroblasts that express NeuroD and that migrate from the antero-ventral, otic epithelium at E9.5-10.5. On the medial side, neuroblasts and epithelial cells express GATA3 but on the lateral side they do not. At E13.5 most auditory neurons express GATA3 but no longer express NeuroD, whereas vestibular neurons express NeuroD but not GATA3. Neuroblasts expressing NeuroD and GATA3 were located in the ventral, otic epithelium, the adjacent mesenchyme and the developing auditory ganglion. The results suggest that auditory and vestibular neurons arise from different, otic epithelial domains and that they gain their identity prior to migration. In auditory neuroblasts, NeuroD appears to be dependent on the expression of GATA3.

The metabolism of glutamate, the most likely neurotransmitter of vestibular ganglion cells, includes synthesis from glutamine by the enzyme glutaminase. We used microdissection combined with a fluorometric assay to measure glutaminase activity in the vestibular nerve root and nuclei of rats with unilateral vestibular ganglionectomy. Glutaminase activity in the lesioned-side vestibular nerve root decreased by 62% at 4 days after ganglionectomy and remained at similar values through 30 days. No change occurred in the contralateral vestibular nerve root. Glutaminase activity changes in the vestibular nuclei were lesser in magnitude and more complex, including contralateral increases as well as ipsilateral decreases. At 4 days after ganglionectomy, glutaminase activity was 10-20% lower in individual lesioned-side nuclei compared with their contralateral counterparts. By 14 and 30 days after ganglionectomy, there were no statistically significant differences between the nuclei on the two sides. This transient asymmetry of glutaminase activities in the vestibular nuclei contrasts with the sustained asymmetry in the vestibular nerve root and suggests that intrinsic, commissural, or descending pathways are involved in the recovery of chemical symmetry. This recovery resembles our previous finding for glutamate concentrations in the vestibular nuclei and may partially underlie central vestibular compensation after peripheral lesions.

Sense organ deposits have been described in temporal bones from patients with vestibular neuronitis, Meniere's disease, and benign paroxysmal positional vertigo that are not found in a comparable series of temporal bones without vestibulopathy. Because the recurrent vestibulopathies are caused by vestibular ganglionitis and the vestibulocochlear anastomosis was degenerated in these temporal bones, the deposits may represent the end buds of regenerating efferent axons injured in passage through the vestibular ganglion. Such neural buds have been described with transmission electron microscopy in animals after vestibular nerve transection and in a human temporal bone with endolymphatic hydrops. The buds may be visible by light microscopy, because their size is comparable to that of hair cell nuclei and they stain blue with hematoxylin because of their nucleic acid content. The variable location and size of these deposits (buds) in the labyrinthine sense organs is described to aid in the recognition of efferent system injury in human temporal bones.

We performed an immunohistochemical investigation of the distribution of glucocorticoid receptors (GRs) in the murine inner ear and found that GRs were expressed extensively, but with various degrees of immunoreactivity in different regions. We observed the strongest GR expression in the type III fibrocytes of the spiral ligament. Although the immunoreactivity of the cochlear hair cells and of the vestibular sensory epithelia was weak, the neighboring cochlear supporting cells and the subepithelial regions of the vestibular sensory epithelia were immunostained. Staining for GRs was also positive in the spiral ganglia and vestibular ganglia, as well as in the endolymphatic sac. The role of GRs in the inner ear is discussed.

Object. The authors studied the cadaveric heads of 22 adults to describe the internal acoustic meatus (IAM) and its contents. Special attention was paid to the length of the arachnoidal and dural sheaths surrounding the neural structures, including the vestibular ganglion. An additional goal of this study was to verify anatomically the concept of arachnoidal duplication, which is reputedly induced by medial growth of vestibular neuromas and helpful in atraumatic dissection. Methods. Twelve cadaveric heads (24 IAMs) were injected with colored latex and fixed in formalin. Cautious removal of the skull vault and the brain or the skull base allowed superior and anteroinferior views of the IAM, respectively. Photographs were obtained after removal of the bone canal and dissection of the meninges with the aid of optic magnification. Ten IAMs were prepared for histological study and the osteological anatomy of the fundus was endoscopically described for the remaining 10. The dura mater covered the bone structures of the IAM, and the arachnoidal membrane of the cerebellopontine cistern invaginated into this dural cul-de-sac as a “muff.” The entire neurovascular content of the IAM, including the vestibular ganglion, was surrounded by this arachnoidal sheath in which cerebrospinal fluid circulated. The length of this arachnoidal sheath was the same ventrally and dorsally and, in all specimens, the entrance of the cochleovestibulofacial complex into the subarachnoid space was located at the fundus level. Conclusions. In this study the authors demonstrated the existence of an acousticofacial cistern containing every nerve of the vestibulocochleofacial complex, including the vestibular ganglion from which acoustic neuromas develop. These findings clearly contradict the theory of the duplication of arachnoidal layers during medial growth of vestibular neuromas and may explain some of the intraoperative difficulties encountered in the atraumatic dissection of these tumors.

Ramsay Hunt’s hypothesis that herpes zoster oticus results from reactivation of the varicella zoster virus (VZV) in the geniculate ganglion is supported by the detection of viral genome in archival temporal bones of normals and Ramsay Hunt patients by the polymerase chain reaction. Ramsay Hunt syndrome is characterized by the presence of cochleovestibular symptoms in association with facial paralysis. VZV has also been demonstrated in the spiral and/or vestibular ganglion. Two cases are reported in which cochleovestibular symptoms outweighed the facial nerve symptoms, presumably representing VZV reactivation in the spiral and/or vestibular ganglion. From these observations and the known dormancy of VZV in non-neuronal satellite cells, it is argued that the cochleovestibular symptoms in Ramsay Hunt syndrome may result from VZV transmission across the nerves inside the internal auditory canal and that prompt treatment with an antiviral-corticosteroid combination might be justified in the management of any acute non-hydropic cochleovestibular syndrome.

An unambiguous delineation of the exact numbers and/or proportions of calyx-only, dimorph, and bouton-only vestibular afferents is needed to continue studies concerning vestibular integration in the nervous system. Here, we take advantage of immunocytochemical properties of three groups of vestibular afferents. We utilize calretinin to delineate the calyx-only population, and peripherin to stain the bouton-only afferents. An additional subgroup of afferents that stain with calbindin, but not calretinin is also introduced. The size of the cells that stain with these markers was determined. Cells that are calbindin-positive overlap the sizes of Nissl-stained somata. Cells that stain with peripherin or calretinin are non-overlapping with calretinin cells being the largest and peripherin-positive cells the smallest. Twenty percent of the ganglion cells were peripherin positive, another 20% stained with calretinin antibodies, 30% stained with calbindin, and all cells in Scarpa’s ganglion stained with parvalbumin. Most of the calretinin-positive cells also stained with calbindin. One-third of the calbindin-positive population stained only with calbindin. These studies indicate that the calyx- and bouton-only populations of vestibular afferents in gerbil comprise at least 40% of the nerve. In addition, at least 10% of the nerve also stains with calbindin and neither calretinin nor peripherin. Based on indirect evidence, we hypothesize that these are a subpopulation of dimorph afferents. This study has provided an anatomical instrument (in addition to intracellular physiological methods) to study separate populations of vestibular afferents.

Vestibular nerve branches innervating the sensory epithelia of the three semicircular canals or of the three otolith organs of frogs were selectively labeled in-vitro with biocytin. Labeled afferent fibers from the semicircular canals, utricle, and lagena were encountered in each of the four vestibular nuclei and their projections overlapped considerably. Saccular afferent fibers projected to the dorsal (acoustic) nuclei and smaller projections to the vestibular nuclei were regionally restricted. Per semicircular canal or otolith organ about equal numbers (11-14) of medium sized vestibular neurons (between 7.5 and 17 microm in diameter) were dye-coupled to afferent fibers. Most of these dye-coupled vestibular neurons were located in the lateral and descending vestibular nuclei between the VIIIth and IXth nerves. The superior vestibular nucleus was relatively free of dye-coupled vestibular neurons. The location of this subpopulation of central vestibular neurons supports the notion that these neurons are part of a particular vestibulospinal pathway. In addition, from each of the canal and/or otolith organs about 3-4 efferent vestibular neurons were labeled retrogradely. These neurons (between 15 and 26 microm in diameter) were located ventral to the vestibular nuclear complex. The branching of efferent vestibular neurons was shown by the presence of neurons that were double labeled by two different fluorescent dyes applied in the same experiment to the anterior and posterior ramus of the same VIIIth nerve, respectively. The branching of these efferent neuron axons explained the presence of collaterals and terminals in the sensory epithelia of a number of untreated ipsilateral endorgans.

This study presents the first direct evidence for herpes simplex virus type 1 (HSV-1) infection in the neurons of the vestibular ganglion. Although many investigators have reported electron microscopic evidence of HSV-1 infection in sensory ganglia, HSV-1 infection in the vestibular ganglion has not been described. Vestibular ganglion neurons have a unique structure, with a loose myelin sheath instead of the satellite cell sheath that is seen in other ganglia. This loose myelin is slightly different from compact myelin which is known as too tight for HSV-1 to penetrate. The role of loose myelin in terms of HSV-1 infection is completely unknown. Therefore, in an attempt to evaluate the role of loose myelin in HSV-1 infection, we looked for HSV-1 particles, or any effects mediated by HSV-1, in the vestibular ganglion as compared with the geniculate ganglion. At the light microscopic level, some neurons with vacuolar changes were observed, mainly in the distal portion of the vestibular ganglion where the communicating branch from the geniculate ganglion enters. At the electron microscopic level, vacuoles, dilated rough endoplasmic reticulum and Golgi vesicles occupied by virus were observed in both ganglia neurons. In contrast, viral infections in Schwann and satellite cells were observed only in the geniculate ganglion, but not in the vestibular ganglion. These results suggest that loose myelin is an important barrier to HSV-1 infection, and it must play an important role in the prevention of viral spread from infected neurons to other cells.

Dysequilibrium of aging in humans has been speculated to arise from progressive deterioration within anatomical components of the vestibular system. An integral part of this system is vestibular ganglions, which are bipolar neurons that relay peripheral vestibular information to the central nervous system. To assess the effect of aging on the number of human vestibular ganglion neurons, assumption-free stereology in the form of the optical fractionator was used on 20 serially sectioned archival human temporal bone specimens. Donors had no history of vestibular pathology and ranged in age from 2 to 88 years. An average of 25,812 (coefficient of variation = 0.13) vestibular ganglion neurons was found throughout this age range, a significant departure from the results of past studies. Logistics-based regression analysis pointed to a nonlinear pattern of decline in the neuronal population: the number of cells remained roughly constant at about 28,952 cells in youth and then declined gradually between 30 and 60 years of age before leveling off at approximately 23,349 cells in older individuals. This study confirmed the existence of an age-related decline in the primary neurons of the human vestibular system, thus providing one anatomical basis for the increased incidence of imbalance seen with age. J. Comp. Neurol. 431:437–443, 2001. © 2001 Wiley-Liss, Inc.

Quantitative assessments of vestibular hair cells and Scarpa's ganglion cells were performed on 17 temporal bones from 10 individuals who had well-documented clinical evidence of aminoglycoside ototoxicity (streptomycin, kanamycin, and neomycin). Assessment of vestibular hair cells was performed by Nomarski (differential interference contrast) microscopy. Hair cell counts were expressed as densities (number of cells per 0.01 mm2 surface area of the sensory epithelium). The results were compared with age-matched normal data. Streptomycin caused a significant loss of both type I and type II hair cells in all 5 vestibular sense organs. In comparing the ototoxic effect on type I versus type II hair cells, there was greater type I hair cell loss for all 3 cristae, but not for the maculae. The vestibular ototoxic effects of kanamycin appeared to be similar to those of streptomycin, but the small sample size precluded definitive conclusions from being made. Neomycin did not cause loss of vestibular hair cells. Within the limits of this study (maximum postototoxicity survival time of 12 months), there was no significant loss of Scarpa's ganglion cells for any of the 3 drugs. The findings have implications in several clinical areas, including the correlation of vestibular test results to pathological findings, the rehabilitation of patients with vestibular ototoxicity, the use of aminoglycosides to treat Meniere's disease, and the development of a vestibular prosthesis.

Scarpa's ganglion cell counts were performed in 106 serially sectioned, normal human temporal bones from 75 individuals. Of these 106 bones, 15 were from neonates less than 30 days old, 14 were from infants between the ages of 1 and 12 months, and the remainder were distributed throughout each decade of life, with sample sizes ranging from 4 to 10 per decade. All temporal bones had to meet 2 criteria: no symptoms or signs of inner ear disease except for presbycusis in the medical case history and no abnormality in the inner ear on light microscopy. The total ganglion cell counts declined significantly with age at an average rate of 57 cells per year. The age-related decline was significantly greater in the superior division than in the inferior division. There was also a significant sex effect, independent of age: for any age, the count in men averaged 1,526 cells higher than in women. There was no significant interaural difference. Mathematical models were developed to compute the mean and 95% prediction intervals for Scarpa's ganglion cell counts in terms of age and sex parameters. The counts and models will serve as a normative database against which to compare counts made in temporal bones from subjects with known vestibular disorders.

The morphology and immunohistochemistry of inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-kappa B) were studied on the spiral and vestibular ganglion of young and old ddy mice. The significant decrease in the number of the spiral ganglion cells and a significant expression of iNOS and NF-kappa B were observed in old mice. In contrast, in the vestibular ganglion of all animals examined, decrease in the number of the ganglion cells or expression of iNOS and NF-kappa B were not observed. Although the relevance of enzymatic systems for the protection of vestibular ganglion cells in old individuals from harmful oxidative stress increased with aging should be further clarified, lack of harmful stress due to nitric oxide (NO) may be one of the plausible reasons for that the vestibular ganglion cells were not decreased in number with aging, since iNOS was not detected in the vestibular ganglion cells in the animals tested in the present study.

Vestibular neuritis is a common cause of partial unilateral vestibular paralysis, which usually spares posterior semicircular canal function. The cause is assumed to be a viral reactivation of latent herpes simplex virus type 1 (HSV-1) in human vestibular ganglia. The existence of an anastomosis between the intermediate nerve and the superior vestibular nerve suggests the question of whether selective affliction of the superior vestibular nerve is the result of migration of HSV-1 from the geniculate ganglion along this faciovestibular anastomosis. We determined the distribution of HSV-1 among geniculate ganglia, vestibular ganglia, and within Scarpa's ganglion by examining 35 human temporal bones by polymerase chain reaction. HSV-1 was found in 66% of geniculate ganglia and 60% of vestibular ganglia; all examined parts of vestibular ganglia were almost equally HSV-1 infected. Our data provided no support for viral migration along this anastomosis or for a preferential latency of HSV-1 in the superior vestibular nerve. We suggest that the common double innervation of the posterior ampulla by two nerves running in two separate bony canals could offer an alternative explanation for the regular sparing of posterior canal function in vestibular neuritis.

Recent morphophysiological studies have described three different subpopulations of vestibular afferents. The purpose of this study was to determine whether peripherin, a 56-kDa type III intermediate filament protein present in small sensory neurons in dorsal root ganglion and spiral ganglion cells, would also label thin vestibular afferents. Peripherin immunohistochemistry was done on vestibular sensory organs (cristae ampullares, utriculi and sacculi) of chinchillas, rats, and mice. In these sensory organs, immunoreactivity was confined to the extrastriolar region of the utriculus and the peripheral region of the crista. The labelled terminals were all boutons, except for an occasional calyx. In vestibular ganglia, immunoreactivity was restricted to small vestibular ganglion cells with thin axons. The immunoreactive central axons of vestibular ganglion cells form narrow bundles as they pass through the caudal spinal trigeminal tract. As they exit this tract, several bundles coalesce to form a single, narrow bundle passing caudally through the ventral part of the lateral vestibular nucleus. Finally, we conclude that all labelled axons and terminals were vestibular afferents rather than efferents, as no immunoreactivity in the vestibular efferent nucleus of the brainstem was observed.

The subpopulation of primary vestibular afferents (PVA) displaying immunoreactivity for the calcium binding protein Calbindin D-28k (Calb) is constituted of particularly large bipolar neurons in the vestibular ganglion (VG) that innervate the central regions of the vestibular end organs exclusively via calyx endings on type I vestibular hair cells. These large-diameter PVA are characterized by irregular spontaneous discharge patterns and predominantly phasic firing properties with respect to natural vestibular stimulation. The present study describes the complete course and terminations of Calb+ PVA in the cerebellar cortex, the cerebellar (CN) and vestibular nuclei (VN) of the mouse. To eliminate the two sources of Calb+ fibers in the cerebellum, i.e., the Calb+ primary vestibular input and the axons of cerebellar Purkinje cells (PC), in their totality, a unilateral eighth nerve transection was performed in the PC-deficient mutant mice, Purkinje cell degeneration (pcd/pcd) and Lurcher (Lc/+). Neurectomy in these mutants results in a complete ipsilateral loss of Calb+ fibers in the cerebellar cortex, the CN and VN. The Calb+ primary vestibular input on the contralateral side terminates solely in the rostral half of the ventral uvula and in the nodulus of the cerebellar cortex. Calb+ fibers traverse all three subdivisions of the CN, but terminations were found only in the lateral and medial cerebellar nuclei. In the VN, Calb+ PVA terminations were restricted to the superior, the ventral part of the lateral, the lateral portion of the medial, and the inferior vestibular nuclei. Calb + terminals were also present in the small cell group Y and Cajal's interstitial nucleus of the vestibular nerve as well as in defined areas of the reticular formation. All Calb + PVA are strictly unilateral. The results show that the Calb+ subpopulation of VG neurons is the sole source of Calb+ fibers and terminals in the PC-deficient cerebellum and the VN. The central input of this distinct subgroup of PVA is distributed in narrow posterior vermal areas and parts of the CN and VN. The cerebellar mutants, Purkinje cell degeneration and Lurcher, provide excellent tools to selectively investigate the subgroup of Calb+ PVA in the mouse in its entirety.

Sixty patients with acute idiopathic vestibular neuritis (confirmed by clinical examination and caloric irrigation) were evaluated in a prospective study by high resolution magnetic resonance imaging (hr-MRI) between days 3 and 30 after onset of symptoms. We used a 1.5 Tesla imager with an axial and coronal Tl-weighted 2D-fast low angle shot-, T2-weighted turbo spin echo-, and an axial T2-weighted 3D-constructive interference in steady-state sequence for MRI. None of the patients' MRIs exhibited contrast enhancement of the labyrinth, vestibulocochlear nerve, or vestibular ganglion, even when high doses of gadolinium (0.2 mmol/kg) were used. In contrast, several previous studies demonstrated contrast enhancement of the vestibulocochlear nerve/labyrinth in herpes zoster oticus, labyrinthitis, and Cogan's syndrome or of the facial nerve in Bell's palsy. On the basis of our MRI findings, we speculate that idiopathic vestibular neuritis is neither a viral infection directly affecting the nerve (such as herpes zoster) nor a labyrinthitis. An autoimmunological disease of the labyrinth, which should involve only the anterior and horizontal semicircular canals, is also unlikely. A subacute reactivation of a latent viral infection-as discussed for Bell's palsy-is compatible with our MRI findings. The observed differences between contrast enhancement of the facial nerve in Bell's palsy and the vestibulocochlear nerve in vestibular neuritis may be due to their dissimilar anatomy: contrary to the vestibular nerve, the facial nerve has very prominent circumneural arteriovenous structures. Hyperemia within these vascular structures may cause the contrast enhancement seen in Bell's palsy.

On the basis that neurotrophins (NTs) affect neuronal synaptic plasticity, are expressed in various cell types of the vestibular system, and exert a trophic influence on statoacoustic neurons, the authors hypothesized a role for NTs in vestibular compensation. To test this hypothesis, they performed unilateral surgical labyrinthectomy in 11 heterozygous (+/-) neurotrophin 3 (NT3) and brain-derived neurotrophic factor (BDNF) knockout mice and in two neurotrophin 4 (NT4) homozygous (-/-) knockout mice, each with a control (+/+) sibling, for a total of 26 mice. Four BDNF(+/-) and four NT3(+/-) mice with their (+/+) controls each were allowed to recover in a normal lighted room for 3, 7, 14, and 30 days following labyrinthectomy. Two BDNF(+/-) and two NT4(-/-) mice with controls were kept in total darkness for 1- and 16-day survival periods. One NT3(+/-) mouse without a control (which died in surgery) was sacrificed after 16 days in darkness. The behavior of all mice was videorecorded to monitor their recovery. Compared with normal (+/+) littermate controls, NT3(+/-) mice demonstrated a delay in compensation (8 to 10 days) in light surround, whereas NT4(-/-) mice showed only a minor delay in dark surround. Despite a 40% lower vestibular ganglion cell population in BDNF(+/-) mice compared with (+/+) controls, BDNF(+/-) mice did not reveal a detectable delay in recovery following labyrinthectomy. These findings suggest that a 50% loss of NT3 protein significantly affects vestibular recovery in adult mice. Perhaps variations in achieving vestibular compensation in humans may be partly secondary to genetically different NT3 levels in vestibular pathways.

Vestibular sensory information from the labyrinth and otolith organs is conducted to the central nervous system exclusively via primary vestibular afferents (PVA) originating from neurons located in the vestibular ganglion (VG). In the present study, the total number of VG neurons was determined in two different wild-type mouse strains using the principles of unbiased stereological counting methods by means of the physical disector. 3316 (±225 SD) neurons were present in the VG of the B6CBA-strain and 3551 (±239 SD) in C57BL/6J-mice. Since no statistical difference was detected between the two strains, the pooled mean number was 3433 (±232 SD) neurons. This is the first unbiased estimate of VG neurons aimed at providing a numerical basis for comparative studies and for the impact of experimental, pharmacological and pathological conditions as well as ageing on the survival and maintenance of VG neurons.

Postnatal development of the peripheral vestibular system and surrounding components in the gerbil was studied to obtain topological information for electrical vestibular stimulation. At postnatal day 1, the peripheral vestibular nerve had already reached the vestibular apparatus. The central vestibular nerve extended posteriorly to enter the brainstem at a sharp angle to anterior-posterior axis. During development, the vestibular ganglion was progressively displaced caudally, along with the vestibular nerve and the ventrally located facial nerve, increasing the angle to the anterior-posterior axis to nearly 90° by postnatal day 30. Contact between the anterior part of the vestibular ganglion and the facial nerve, and that between the posterior part of the ganglion and the cochlear nerve were observed at all ages. These regions were considered unsuitable for electrical stimulation because of the high risk of stimulating the facial or cochlear nerve, similar to those regions in the adult. These results as well as the observation that the diameter of the lateral semicircular canal remained nearly constant showed that the technique we used for electrical vestibular stimulation in adult animals was apparently a good choice in younger animals as well.

Analysis of trkB−/−; trkC−/− double mutant mice revealed that peripheral and central inner ear sensory neurons are affected in these mice. However, a substantial amount of cochlear and vestibular neurons survive, possibly due to maintenance or upregulation of TrkA expression. To clarify the function of the TrkA receptor during development of the cochlear and vestibular ganglion we analysed trkA−/− mice and the expression of this receptor in inner ear sensory neurons of trkB−/−; trkC−/− animals. TrkA homozygous mutant mice showed normal numbers of neurons and no TrkA expression was detected in neurons of trkB−/−; trkC−/− double mutant mice. We conclude that TrkA is not essential for inner ear development and that in the absence of any of the known catalytic Trk receptors peripheral inner ear sensory neurons are prone to undergo cell death or must use a different signaling mechanism to survive.