Eighth Nerve Research Articles

か牛神経または下部脳幹障害例のＡＢＲ診断について

か牛神経または下部脳幹障害例のＡＢＲ診断について

Distribution of calcitonin gene-related peptide mRNA and immunoreactivity in the rat central and peripheral vestibular system.

The distribution of calcitonin gene-related peptide (CGRP) mRNA and immunoreactivity (CGRPi) was examined in sections of brainstem and decalcified temporal bones to study the peptidergic innervation patterns in both the central and peripheral vestibular system. In the brainstem, neuron somata associated with the vestibular system and containing CGRP mRNA and CGRPi were found in both the dorsolateral and medial regions of the group E vestibular efferents as well as scattered throughout the caudal pontine reticular nucleus (CPR). The only labelled neuron somata containing CGRP mRNA and CGRPi in the temporal bone were found in the gustatory geniculate ganglion. Coarse CGRPi axons were traced ventrally from the dorsolateral and medial group E somata and dorsally from the CPR somata. CGRPi axons from the medial group E and CPR crossed the facial nerve ventral to the facial genu before entering the eighth nerve root. Immunoreactive axons projected from medial group E cells, beneath the ependyma of the fourth ventricle, to the contralateral brainstem. Unmyelinated CGRPi fibers passed among the primary afferent fibers in Scarpa's ganglion and continued through the subepithelial regions of the vestibular end-organs. Within the neurosensory epithelia of the maculae and cristae, the CGRPi axons ramified to produce numerous CGRPi terminals. An efferent neuromodulatory role of CGRP in the vestibular system is inferred from the wide distribution of CGRP mRNA and immunoreactivity found within efferent vestibular neurons.

Dopamine enhances both electrotonic coupling and chemical excitatory postsynaptic potentials at mixed synapses.

The transmitter dopamine reduces electrotonic coupling between retinal horizontal cells and increases their sensitivity to glutamate. Since in other systems single afferents establish mixed electrotonic and chemical excitatory synapses with their targets, dopamine might be expected there to depress one component of excitation while enhancing the other. This hypothesis was tested by applying dopamine locally in the vicinity of the lateral dendrite of the goldfish Mauthner cell (M cell) and monitoring the composite electrotonic and chemical excitatory postsynaptic potentials and currents evoked by ipsilateral eighth nerve stimulation. Dopamine produces persistent enhancements of both components of the postsynaptic response while it also increases input conductance. All these dopamine actions are prevented by superfusing the brain with saline containing the dopamine D1 receptor antagonist SCH-23390. Postsynaptic injections of the cAMP-dependent protein kinase inhibitor (Walsh inhibitor, or PKI5-24) block the dopamine-induced changes in synaptic transmission, implicating a cAMP-dependent mechanism. Furthermore, there is a dopaminergic innervation of the M cell, as demonstrated immunohistochemically with antibodies against dopamine and the rate-limiting enzyme in its synthetic pathway, tyrosine hydroxylase. Varicose immunoreactive fibers lie in the vicinity of the distal part of the lateral dendrite between the large myelinated club endings that establish the mixed synapses. As determined with electron microscopy, the dopaminergic fibers contain small vesicles, and they do not have synaptic contacts with either the afferents or the M cell, remaining instead in the synaptic bed. Taken together, these results suggest that dopamine released at a distance from these terminals increases the gain of this primary sensory input to the M cell, most likely through a phosphorylation mechanism.

Diameter of the cochlear nerve in deaf humans: implications for cochlear implantation.

Although the parameters that are most important for postoperative speech perception in cochlear implantation have not been identified, it is assumed that the numbers of remaining cochlear neurons and spiral ganglion cells in the implanted deaf ears are critical. In this study, we evaluated the correlation of the maximum diameter of the cochlear and vestibular nerve trunks with the number of spiral ganglion cells in horizontal sections of the temporal bone of 42 patients who were profoundly deaf during life, and in 5 patients with normal hearing. The maximum diameters of the cochlear, vestibular, and eighth cranial nerves were significantly smaller in the deaf population as compared to normal-hearing controls. In addition, the counts of the remaining spiral ganglion cells were significantly correlated with the maximum diameter of the cochlear (p = .0006), vestibular (p = .001), and eighth cranial nerves (p = .0003). The regression equation estimated that 25% of the variance of the spiral ganglion cell count was predicted by the maximum diameter of the eighth nerve. Although the results of this study suggest that preoperative radiographic imaging of the diameter of the eighth nerve may be helpful in predicting the residual spiral ganglion cell count, the wide variability of diameters of the eighth nerve in hearing and deaf subjects militates against this theoretic usefulness.

Heterogeneity of sensory hair cells in a fish ear.

The ultrastructure of sensory hair cells in the utricle of the cichlid fish, Astronotus ocellatus, the oscar, was studied by transmission electron microscopy of serial ultrathin sections from different regions of the epithelium. Two distinctly different types of hair cell were found, one located in the striolar region of the epithelium and the other in the extrastriolar region. Striolar hair cells have a well-defined perinuclear cisterna located just below the nucleus, and large perinuclear mitochondria. Synaptic bodies of striolar cells are small and located in clusters, while those in extrastriolar cells are relatively large and individually dispersed. The extrastriolar hair cell closely resembles the amniote type II hair cell. On the basis of these data, and consistent with earlier studies, it appears that the striolar hair cells closely resemble amniote type I hair cells in many significant ways. Thus we have called them type I-like cells. The extrastriolar hair cells appear to be typical of eighth nerve mechanoreceptors commonly described for fish and closely resemble the amniote type II hair cell.

A comparison of anesthetic agents and their effects on the response properties of the peripheral auditory system

Anesthetic agents were compared in order to identify the most appropriate agent for use during surgery and electrophysiological recordings in the auditory system of the tokay gecko ( Gekko gecko). Each agent was first screened for anesthetic and analgesic properties and, if found satisfactory, it was subsequently tested in electrophysiological recordings in the auditory nerve. The following anesthetic agents fulfilled our criteria and were selected for further screening: sodium pentobarbital (60 mg/kg); sodium pentobarbital (30 mg/kg) and oxymorphone (1 mg/kg); 3.2% isoflurane; ketamine (440 mg/kg) and oxymorphone (1 mg/kg). These agents were subsequently compared on the basis of their effect on standard response properties of auditory nerve fibers. Our results verified that different anesthetic agents can have significant effects on most of the parameters commonly used in describing the basic response properties of the auditory system in vertebrates. We therefore conclude from this study that the selection of an appropriate experimental protocol is critical and must take into consideration the effects of anesthesia on auditory responsiveness. In the tokay gecko, we recommend 3.2% isoflurane for general surgical procedures; and for electrophysiological recordings in the eighth nerve we recommend barbituate anesthesia of appropriate dosage in combination if possible with an opioid agent to provide additional analgesic action.

Lipoma of Internal Auditory Canal

Lipoma of the internal auditory canal is a rare tumor. Clinically, it presents like an acoustic tumor. The diagnosis can be made with the use of a magnetic resonance imaging showing a high intensity on T1- and low intensity on T2-weighted image with no enhancement. Pathologically, this is a soft, smooth, yellow tumor with some fat in it that can resemble grossly any acoustic tumor. The lipoma is intermixed with the eighth nerve and can be adherent to adjacent structures. The growth of a lipoma can be slower than an acoustic tumor. A patient diagnosed with lipoma of the internal auditory canal can often have quite good hearing. As an alternative to surgical removal, another therapeutic option is to watch the growth of the lipoma with periodic magnetic resonance imaging, probably on a yearly basis initially.

Correlations of neuroanatomical measures to auditory brain stem response latencies.

Magnetic resonance imaging (MRI) was used to obtain measures presumed to scale the dimensions of the lower auditory pathway in humans for the purpose of further defining the relationship between length of the auditory pathway and auditory brain stem response (ABR) latencies. Specifically, measurements of soft tissue structures, that is, the eighth nerve and brain stem, were made for comparison with skull dimensions and ABR latencies. It was hypothesized that the brain stem dimensions covary significantly with skull dimensions and that the ABR parameters covary with both skull and brain stem dimensions. In general, only weak correlations were obtained with coefficients failing to reach statistical significance for most comparisons. These findings suggest that variance in ABR latencies cannot be attributed completely to variance in brain stem dimensions and raise suspicion that skull dimensions do not directly reflect brain stem dimensions.

Physiological and behavioral identification of vestibular nucleus neurons mediating the horizontal vestibuloocular reflex in trained rhesus monkeys.

1. To describe in detail the secondary neurons of the horizontal vestibuloocular reflex (VOR), we recorded the extracellular activity of neurons in the rostral medial vestibular nucleus of alert, trained rhesus monkeys. On the basis of their activity during horizontal head and eye movements, neurons were divided into several different types. Position-vestibular-pause (PVP) units discharged in relation to head velocity, eye velocity, eye position, and ceased firing during some saccades. Eye and head velocity (EHV) units discharged in relation to eye velocity and head velocity in the same direction so that the two signals partially canceled during the VOR. Two cell types discharged in relation to eye position and velocity but not head velocity; other types discharged in relation to head velocity only. 2. The position in the neural path from the primary vestibular afferents to abducens motoneurons was examined for each type. Direct input from the vestibular nerve was indicated if the cell could be activated by shocks to the nerve at latencies less than or equal to 1.4 ms. A projection to abducens motoneurons was indicated if spike-triggered averaging of lateral rectus electromyographic (EMG) activity yielded responses with a sharp onset at monosynaptic latencies. 3. PVP neurons were the principal interneuron in the VOR "three-neuron arc." Eighty percent received primary afferent input, and 66% made excitatory connections with contralateral abducens motoneurons. Surprisingly few, approximately 11%, made inhibitory connections with ipsilateral abducens motoneurons. This imbalance in the ipsi- and contralateral projections was confirmed by measuring the EMG activity evoked by electrical microstimulation in regions where PVP neurons were located. 4. EHV neurons whose activity increased during contralaterally directed head or eye movements were also interneurons in the ipsilateral inhibitory pathway. Eighty-nine percent received ipsilateral primary afferent input, and 25% projected to ipsilateral abducens motoneurons. EHV neurons excited during ipsilateral movements received neither direct primary afferent input nor projected to either abducens nucleus. A small proportion of each of two other cell types having sensitivity to contralateral eye position made excitatory connections with contralateral abducens motoneurons. Other types rarely were activated from the eighth nerve or projected to the abducens nucleus. 5. The significance of the connections of VOR interneurons and the signals they convey is discussed for three situations: smooth pursuit of a moving target, suppression of the VOR, and the VOR itself. PVP neurons convey a signal with a ratio of eye position and velocity components that is inappropriate to drive motoneurons during pursuit or the VOR.(ABSTRACT TRUNCATED AT 400 WORDS)

Rapid changes in protein synthesis and cell size in the cochlear nucleus following eighth nerve activity blockade or cochlea ablation.

Destruction of the cochlea causes secondary changes in the central auditory pathway through transynaptic regulation. These changes appear to be mediated by an activity-dependent process and can be detected in the avian auditory system as early as 30 minutes after deafferentation. We compared the early changes in cochlear nucleus neurons following deafferentation by cochlea ablation with those seen following activity deprivation by perilymphatic tetrodotoxin (TTX) exposure. Protein synthesis and size of large spherical cells in the anteroventral cochlear nucleus (AVCN) of 14-day-old gerbils were measured during the first 48 hours after the manipulations. Both cochlea ablation and TTX produced a reliable decrease in protein synthesis by AVCN neurons (30-40%) by 1 hour. The magnitude of change in tritiated leucine incorporation was similar at all survival times, in both experimental groups. In contrast to the rapid changes in protein synthesis, the decrease in cell size was first evident 18 hours after TTX exposure and 48 hours after cochlea ablation. There was no significant change in protein synthesis or cell size in control groups at any of the survival times. These findings are consistent with changes in the avian auditory system in response to deafferentation and TTX exposure. Cochlea ablation and TTX exposure induced similar transneuronal changes, supporting the hypotheses that activity of auditory afferents in young mammals plays a regulatory role in the metabolism and morphology of their target neurons in the central auditory pathway, and that early changes following destruction of the peripheral receptor are due to reduction of activity-dependent interactions of presynaptic and postsynaptic cells.

Directionality of phase locking in auditory nerve fibers of the leopard frog Rana pipiens pipiens.

A dorsal approach to the eighth nerve and free-field stimulation were used to investigate the effect of sound direction and intensity on phase locking in auditory nerve fibers of the leopard frog Rana pipiens pipiens. Tuning curves of 75 auditory neurons were analyzed (Fig. 2). Amphibian papillar neurons, but not basilar papillar neurons, exhibit significant phase locking to short tone bursts at the characteristic frequency (CF), the degree of phase locking (vector strength) decreasing with the neuron's CF (Figs. 3, 4 and 10E). Vector strength increases with sound pressure level to saturate about 20 dB above threshold, while the preferred firing phase is only slightly affected (Figs. 5 and 6). In contrast, sound direction hardly affects vector strength (Figs. 7, 8, 9A and 10A and C), but has a strong influence on the preferred firing phase (Figs. 7, 8, 9B and C, 10B and D): With respect to anterior tone presentation there are phase lags for ipsilateral and phase leads for posterior and contralateral presentation. Phase differences between both ears show a sinusoidal or cardioid/ovoidal directional characteristic; maximum differences are found with antero-lateral tone presentation (Fig. 11). The directionality of phase locking decreases with the neuron's CF (Fig. 10F) and only slightly changes with sound pressure level (Fig. 12). Thus, phase locking of amphibian papilla neurons can potentially provide intensity-independent information for sound localization.

Auditory nerve representation of a complex communication sound in background noise.

A population study of auditory nerve responses in the bullfrog, Rana catesbeiana, analyzed the relative contributions of spectral and temporal coding in representing a complex, species-specific communication signal at different stimulus intensities and in the presence of background noise. At stimulus levels of 70 and 80 dB SPL, levels which approximate that received during communication in the natural environment, average rate profiles plotted over fiber characteristic frequency do not reflect the detailed spectral fine structure of the synthetic call. Rate profiles do not change significantly in the presence of background noise. In ambient (no noise) and low noise conditions, both amphibian papilla and basilar papilla fibers phase lock strongly to the waveform periodicity (fundamental frequency) of the synthetic advertisement call. The higher harmonic spectral fine structure of the synthetic call is not accurately reflected in the timing of fiber firing, because firing is "captured" by the fundamental frequency. Only a small number of fibers synchronize preferentially to any harmonic in the call other than the first, and none synchronize to any higher than the third, even when fiber characteristic frequency is close to one of these higher harmonics. Background noise affects fiber temporal responses in two ways: It can reduce synchronization to the fundamental frequency, until fiber responses are masked; or it can shift synchronization from the fundamental to the second or third harmonic of the call. This second effect results in a preservation of temporal coding at high noise levels. These data suggest that bullfrog eighth nerve fibers extract the waveform periodicity of multiple-harmonic stimuli primarily by a temporal code.

Usefulness of computed tomographic scan in the evaluation of sensorineural hearing loss in children.

A retrospective chart study was conducted to determine the diagnostic yield of temporal bone imaging for children with sensorineural hearing loss of unknown cause. Seventy consecutive cases, spanning 4.5 years, were identified and individual computed tomography films reviewed. Cases were analyzed with respect to patients' age, duration of hearing loss, sudden onset vs progressive loss, unilateral vs bilateral, and other symptoms. Of the 70 computed tomographic scans, nine showed temporal bone or other intracranial abnormalities. The majority of these findings were localized to structures in the posterior and middle cranial fossae. No eight nerve tumors were identified. Congenital hearing loss and hearing loss secondary to viral infections are the most common cause of sensorineural hearing loss when discovered in early childhood and, often, have no radiographic abnormality. The decision to explore an ear for a presumed perilymph fistula is based almost exclusively on the history and physical examination, and not on the demonstration of any radiographic findings. For the children presenting with stable hearing impairment in the absence of other findings, computed tomographic scans were either negative or did not contribute to diagnosis. Since tumors of the eighth nerve are rare in children under 16 years of age (without neurofibromatosis), and radiologic studies have a low yield in identifying perilymph fistulas, the routine use of computed tomographic imaging in such children may be unjustified.

Rapid growth of astrocytic processes in N. magnocellularis following cochlea removal.

Removal of the cochlea or pharmacological blockade of eighth nerve activity in young postnatal chickens results in rapid transneuronal cell death and atrophy in neurons of n. magnocellularis. The present experiments were designed to examine the influence of afferent input on astrocyte structure in n. magnocellularis. Young chickens were subjected to unilateral cochlea removal. At times ranging from 5 minutes to 72 hours later, the brainstems were histologically processed with a polyclonal antibody against glial fibrillary acidic protein (GFAP). A second group of chick brainstems was impregnated by a Golgi method 6 hours after unilateral cochlea removal and impregnated three-dimensional reconstructions were made of glial cells in n. magnocellularis (NM). Analyses of GFAP positive processes in NM revealed an observable increase in the number of astrocytic processes at the borders of the nucleus within 30 minutes of cochlea removal and a twofold increase in GFAP + glial processes by 6 hours. A secondary increase in the number and density of GFAP + processes occurred between 24 and 72 hours following cochlea removal, during the period of axonal degeneration, and transneuronal cell atrophy and death. Analyses of astrocytes impregnated by the Golgi method revealed that individual glial cells had increased their total process length and the number of processes by approximately twofold by 6 hours after cochlea removal. These results suggest that the structure of astrocytes is rapidly and dramatically influenced by the level of excitatory activity in a neuronal system. Furthermore, the similarity of results obtained with GFAP immunohistochemistry and three-dimensional reconstruction of astrocytes provides evidence that the short-term changes observed following cochlea removal represent the actual growth of glial processes. We speculate that modulations in glial processes as a function of afferent activity may act to influence synaptic efficacy.

Electron-microscopic localization of type II, IX, and V collagen in the organ of Corti of the gerbil

The presence of types II, IX and V collagen was probed in the organ of Corti of the adult gerbil cochlea by use of immunocytochemistry at the light- and electron-microscopic levels. Type II collagen is found in the connective tissues of the osseous spiral lamina and spiral limbus. In the region of the sensory hair cells it is present in the tectorial membrane and antibodies bind to the thick unbranched radial fibers. Type IX collagen co-localizes with type II collagen in the tectorial membrane, where antibodies bind to the thick unbranched radial fibers. Type V collagen is present in the connective tissue of the spiral limbus, the osseous spiral lamina, the eighth nerve, and the tectorial membrane. In the tectorial membrane, the staining with antibodies to type V collagen is more diffuse than that seen for types II and IX collagen and antibodies to type V bind to the thin, highly branched fibers in which the thick fibers are embedded. The results indicate that collagens characteristic of cartilage are localized in the organ of Corti. Within the tectorial membrane, types II and IX collagen form heterotypic thick fibers embedded in a reticular network of type V collagen fibers. These collagens form a highly structured matrix which contributes to the rigidity of the tectorial membrane and allow it to withstand the physical stresses associated with transmission of the stimuli necessary for sensory transduction.

Rapid and reversible astrocytic reaction to afferent activity blockade in chick cochlear nucleus

We describe here rapid proliferation of astrocytic processes immunoreactive for glial fibrillary acidic protein (GFAP) in the chick cochlear nucleus following blockade of action potentials in the afferent nerve. Unilateral eighth nerve activity blockade was achieved through intralabyrinthine injection of TTX. Within 1 hr of activity blockade, a 56% increase in area density of GFAP-immunoreactive processes was found in the ipsilateral cochlear nucleus as compared to the contralateral side of the brain. This increase reached 152% by 3 hr. When eighth nerve activity was allowed to recover and animals were studied 1 week after TTX injection, no difference was found in GFAP immunoreactivity between the ipsilateral and contralateral cochlear nuclei. This is the first report of a glial reaction to documented neuronal inactivity in the absence of neuropathology. These results indicate that neuronal activity may regulate the structure of astrocytic processes.

Frequency-specific maturation of the eighth nerve and brain-stem auditory pathway: evidence from derived auditory brain-stem responses (ABRs).

Previous studies of human auditory development using frequency-specific auditory brain-stem responses (ABRs) have reported that maturation for both peak and interpeak latencies occurs earlier for responses generated by low-frequency stimuli. In two of these studies, low-frequency ABRs presumed to originate from apical locations in the cochlea were likely dominated by activity from higher frequency regions closer to the base. In the present study, the high-pass noise-masking technique was used to generate derived ABRs that represent activity from isolated place specific regions along the basilar membrane. Analysis of auditory brain-stem maturation based on I-V interpeak latency differences with adult means revealed a frequency-specific pattern of development. Developmental changes occurred faster and mature function was attained earlier for ABRs from the mid-center-frequency (CF) derived conditions than from either the highest or lowest CF derived conditions. The differential maturation of mid-CF derived ABRs may reflect the delayed effects of the pattern of development that occurs in the cochlea.

Compound action potentials recorded from the exposed eighth nerve in patients with intractable tinnitus

Compound action potentials (CAP) were recorded directly from the exposed intracranial portion of the eighth nerve in 19 patients undergoing microvascular decompression (MVD) of the eighth nerve for intractable tinnitus. The waveform of the CAPs recorded in patients with tinnitus varied from normal to highly abnormal, but only in 1 patient were there distinct abnormalities in the waveform of the CAP that could not be attributed to the patient's hearing loss. The mean values of the latencies of the N1 and N2 peaks in the CAPs recorded from the exposed eighth nerve in patients with tinnitus and high-frequency hearing loss were virtually indistinguishable from the latencies obtained in patients with similar hearing loss but no tinnitus. There was no statistically significant difference between the latency of peak III in the brainstem auditory evoked potentials (BAEPs) in these two groups of patients, but the latency of peak V was slightly shorter (statistically significant) in the patients with tinnitus than it was in the patients without tinnitus.

Sudden Bilateral Profound Hearing Loss Resulting from Meningeal Carcinomatosis

SBPHL is a rare manifestation of hearing loss. Patients with SBPHL should have a thorough evaluation for meningeal carcinomatosis as the cause, including a complete neurologic evaluation, CT scan, and, probably, MRI. If MC is highly suspected, an LP is necessary. Because the diagnosis of MC can be confirmed only by the presence of malignant cells in the CSF, multiple LPs may be necessary to find them. Although MC should be strongly considered in the differential diagnosis of SBPHL, MC should also be considered with other patterns of eighth cranial nerve involvement, especially in patients with a history of malignancy. These patterns include unilateral hearing loss associated with tinnitus, unilateral hearing loss rapidly progressing to severe bilateral involvement, audiologic and caloric studies that show eighth cranial nerve impairment, and facial nerve palsy associated with hearing loss. The prognosis for MC is poor, although intraventricular chemotherapy and whole brain radiotherapy can provide significant palliation.

Regeneration of the eighth cranial nerve in the bullforg, Rana catesbeiana

The present study was done in order to document the ability of the eighth cranial nerve of the bullforg ( Rana catesbeiana) to regenerate, the anatomic characteristics of the regenerated fibers, and the specificity of projections from individual endorgan branches of the nerve. The eighth cranial nerve was sharply transected between the ganglion cells and the brain stem in 40 healthy bullfrogs and allowed to regenerate. Anatomic studies were performed in these animals a minimum of 3 months postoperatively. Horseradish peroxidase was used to label the whole vestibular nerve or its individual endorgan branches. Labeled regenerated fibers could be identified crossing the site of the nerve section and projecting centrally to the vestibular nuclei in a pattern similar to that of normal frogs. Labeling of individual branches showed that regenerated fibers innervated the same specific areas found in normal frogs. Unlike normal animals, both thick and thin fibers projected to the medial nucleus.