Eighth Nerve Research Articles

Cochlear implantation in children with cochlear aplasia

Conclusion: Children with cochlear aplasia can achieve favorable speech perception abilities from cochlear implantation (CI) by inserting an electrode array into the vestibule if an audiological response is reliably demonstrated before surgery by behavioral audiometry and objective measures. Objectives: The purpose of this study was to evaluate the surgical outcome of CI in children with cochlear aplasia. Methods: The medical records of 454 children who underwent CI at the Dong-A University Hospital between January 1994 and September 2011 were reviewed. The prevalence of cochlear aplasia and the preoperative evaluations, operative findings, and postoperative speech perception abilities of implanted children with cochlear aplasia were evaluated. Results: The implanted children with cochlear aplasia accounted for 2% of those with inner ear malformations and 0.4% of all pediatric cochlear implantees. They showed audiological responses in preoperative electrophysiologic tests, and the eighth nerve was present in magnetic resonance imaging. The electrode array was inserted into the vestibule through an oval window after removing the stapes or through a transmastoid labyrinthotomy site. Electrical compound action potential and electrical auditory brainstem response tests showed clear neural responses after implantation. The hearing thresholds of the implanted ear improved to 25 dB HL and the children achieved significant open set speech perception abilities.

Embryonic assembly of auditory circuits: spiral ganglion and brainstem

During early development, peripheral sensory systems generate physiological activity prior to exposure to normal environmental stimuli. This activity is thought to facilitate maturation of these neurons and their connections, perhaps even promoting efficacy or modifying downstream circuitry. In the mammalian auditory system, initial connections form at embryonic ages, but the functional characteristics of these early neural connections have not been assayed. We investigated processes of embryonic auditory development using a whole-head slice preparation that preserved connectivity between peripheral and brainstem stations of the auditory pathway. Transgenic mice expressing fluorescent protein provided observation of spiral ganglion and cochlear nucleus neurons to facilitate targeted electrophysiological recording. Here we demonstrate an apparent peripheral-to-central order for circuit maturation. Spiral ganglion cells acquire action potential-generating capacity at embryonic day 14 (E14), the earliest age tested, and action potential waveforms begin to mature in advance of comparable states for neurons of the ventral cochlear nucleus (VCN) and medial nucleus of the trapezoid body (MNTB). In accordance, auditory nerve synapses in the VCN are functional at E15, prior to VCN connectivity with the MNTB, which occurs at least 1 day later. Spiral ganglion neurons exhibit spontaneous activity at least by E14 and are able to drive third-order auditory brainstem neurons by E17. This activity precedes cochlear-generated wave activity by 4 days and ear canal opening by at least 2 weeks. Together, these findings reveal a previously unknown initial developmental phase for auditory maturation, and further implicate the spiral ganglion as a potential controlling centre in this process.

Ototoxicity of Burow solution on the guinea pig cochlea

Purpose of the studyThe aim of the present study was to evaluate the ototoxicity of Burow solution. ProceduresCompound action potentials (CAPs) of the eighth nerve were measured before and 30 minutes after the application of the Burow solution in the middle ear cavity. ResultsUse of the original Burow solution (pH 3.5) for 30 minutes caused a significant reduction of click sounds. A 2-fold diluted Burow solution (pH 4.4) for 30 minutes caused no reduction in CAP threshold. Burow solution, pH adjusted to 4.5, caused no changes in CAP threshold at 30 minutes. At 24 hours, Burow solution (pH 3.5) caused complete abolition of CAP. ConclusionsBurow solution is ototoxic in the guinea pig when applied in the middle ear cavity for 30 minutes or longer. In the clinical settings, it is advisable to avoid allowing the solution to contact the round window for extended times.

Vascular compression of the cochlear nerve and tinnitus: a pathophysiological investigation

Chronic microvascular compressions of the eighth nerve induce a slowing down of signal transmission in the auditory nerve, electrophysiologically characterized by IPL I-III prolongation. The authors hypothesize this is compensated by an active slowing down of signal transmission of the contralateral input at the level of the brainstem, characterized by contralateral IPL III-V prolongation. Differences between ipsilateral and contralateral IPL I-III and IPL III-V are analyzed before and after microvascular decompression. ABR diagnostic criteria for microvascular compression are ipsilateral IPL I-III prolongation or ipsilateral peak II decrease + ipsilateral IPL I-III prolongation. With IPL I-III as diagnostic criterion, unlike preoperatively the difference between the ipsi- and contralateral IPL I-III is significant postoperatively. When using the stricter diagnostic criterion of IPL I-III + peak II, there is a preoperative significant difference between ipsi- and contralateral IPL I-III, but postoperatively the difference between the ipsi- and contralateral IPL I-III is not significant. Preoperatively, there is a marginal significant difference between the ipsi- and contralateral IPL III-V, which disappears postoperatively.

Pure-tone auditory thresholds are not chronically elevated in multiple sclerosis.

Despite the fact that acute cases of multiple sclerosis (MS)-related pure-tone hearing loss have been reported in the literature, consensus is lacking as to the chronic influences of MS on pure-tone thresholds. Most studies examining such influences have been limited by small sample sizes, lack of statistical comparisons between patients and controls, and confounding of the hearing measure with influences from sex and age. To date, associations between pure-tone thresholds and central MS-related brain lesions have not been assessed. In this study, pure-tone thresholds ranging from 0.5 to 8 kHz were measured in 73 MS patients and 73 individually age- and gender-matched normal controls. In 63 MS patients, correlations were computed between the threshold values and MRI-determined lesion activity in 26 central brain regions. Although thresholds were strongly influenced by sex, age, and tonal frequency, no meaningful influences of MS were discerned. Moreover, no significant association between the threshold values and central MS-related lesion activity was evident in any brain region evaluated. This study, the largest on this topic to use carefully matched control subjects and the sole study to assess relationships between auditory thresholds and central MS-related lesions, strongly suggests that (a) MS is not chronically associated with pure-tone hearing loss and (b) pure-tone thresholds are unrelated to MS lesion activity in higher brain regions. These findings, along with general reports from the literature, support the concept that when MS-related hearing threshold deficits are found, they are episodic and primarily dependent on lesions within the eighth nerve or brainstem.

Evaluation of central neuropathy in patients of chronic renal failure with normal hearing

Aims and Objective: The aim of the study was to study the involvement of inner ear and eighth nerve in patients of chronic renal failure (CRF) with normal hearing. Further, the mean absolute and inter-peak latencies were correlated with the duration of disease, blood urea level, and the severity of the disease. Materials and Methods: A total of 46 patients of CRF with normal hearing (29 males and 17 females) were included in the study. Majority of the patients were in 21 to 40 year age group. Mean absolute latencies of wave I, III, and V, and inter-peak wave latencies I-III, III-V, and I-V were calculated and compared with the mean wave latencies in 15 normal hearing age- and sex-matched control subjects. Student's t test was applied to evaluate the significance of delay in wave latencies. The patients were divided on the basis of the duration of disease (less than 2 years and more than 2 years), blood urea level (less than 200 mg% and more than 200 mg%), and severity of disease (Patients with glomerular filtration rate [GFR] less than 60 mL/min/1.73 m 2 but more than 10 mL and patients with GFR less than 10 mL/min/1.73 m 2). The significant differences between the hearing thresholds of these two groups were assessed using student's t test for unequal samples. Results: There was a statistically significant delay in absolute latencies of wave I, III, and V and inter-peak latencies I-III, III-V, and I-V. Mean wave latencies with values outside mean ± 2 SD of control were considered as abnormal. Abnormal absolute wave latencies and inter-peak latencies were present in 63.05% and 67.39% of cases, respectively. There was a significant delay in mean absolute latency of wave V and mean inter-peak latency of wave I-III, III-V, and I-V in patients of CRF with duration of disease more than 2 years as compared with patients of CRF with duration of disease less than 2 years. There was a significant delay in mean absolute latency of wave III and V and mean inter-peak latency of wave I-III, III-V, and I-V in patients of CRF with blood urea level more than 200 mg% as compared to patients of CRF with blood urea level less than 200 mg%. There was a significant delay in mean absolute latency of wave III and V and mean inter-peak latency of wave I-III, III-V, and I-V in patients of CRF with GFR less than 10 as compared with patients of CRF with GFR less than 60 but more than 10. Conclusion: The study suggests the involvement of central neural axis and auditory end organ in patients of CRF with normal hearing. It further establishes the role of brainstem evoked response audiometry in earlier detection of central neural axis and auditory end organ. As the duration of disease increases, inferior colliculus and auditory pathway is more prone to damage by uremic neuropathy. An increase in blood urea and decrease in GFR (severity of disease) leads to uremic neuropathy causing damage to superior olivary nucleus and inferior colliculus. Increased blood urea also causes delay in inter-peak latencies, suggesting diffuse axonal neuropathy in patients of CRF.

Auditory neuropathy/Auditory dyssynchrony - An underdiagnosed condition: A case report with review of literature

Auditory neuropathy (AN)/auditory dyssynchrony (AD) is a very often missed diagnosis, hence an underdiagnosed condition in clinical practice. Auditory neuropathy is a condition in which patients, on audiologic evaluation, are found to have normal outer hair cell function and abnormal neural function at the level of the eighth nerve. These patients, on clinical testing, are found to have normal otoacoustic emissions, whereas auditory brainstem response audiometry reveals the absence of neural synchrony. Unlike space-occupying lesions, radiologic evaluation reveals normal results. Patients with auditory neuropathy require a different management approach to their auditory and communication problems from approaches used with patients with usual peripheral hearing losses.

Uptake of gentamicin by vestibular efferent neurons and superior olivary complex after transtympanic administration in guinea pigs

Transtympanic administration of gentamicin is a widely accepted and effective approach for treating patients with intractable vertigo. Previous studies have demonstrated the uptake, distribution and effects of gentamicin in peripheral vestibular and cochlear structures after transtympanic injection. However, little is known about whether transtympanically administered gentamicin is trafficked into more central auditory and vestibular structures and its effect on these structures. In this study, we used immunofluorescence to determine the distribution of gentamicin within the auditory and vestibular brainstem. We observed gentamicin immunolabeling bilaterally in the vestibular efferent neurons, and in the superior olivary complex, and ipsilaterally in the cochlear nucleus 24h after transtympanic administration of gentamicin, and that the drug could still be detected in these locations 30 days after injection. In contrast, no gentamicin labeling was detected in the vestibular nuclear complex. In the vestibular efferent neurons and superior olivary complex, gentamicin labeling was detected in the cytoplasm and cell processes, while in the cochlear nucleus gentamicin is mainly localized outside and adjacent to the cell bodies of neurons. Nerve fibers in cochlear nucleus, root of eighth nerve, as well as descending pathways from the superior olivary complex, are also immunolabeled with gentamicin continuously. Based on these data, we hypothesize that retrograde axonal transport of gentamicin is responsible for the distribution of gentamicin in these efferent nuclei including vestibular efferent neurons and superior olivary complex and anterograde axonal transport into the ipsilateral cochlear nucleus.

Characteristics of the anterior lateral line nerve input to the Mauthner cell

The goldfish Mauthner (M-) cells, a bilateral pair of reticulospinal neurons, initiate the auditory evoked escape behavior of teleosts. In an open field the fish reliably turns away from the sound source. This implies that the M-cells are capable of a decision-making process that requires the two cells to receive differential directional inputs. Recent studies have indicated that the lateral line (LL) system is necessary in the initial directionality of the escape. This information is thought to be transmitted to the M-cell by the anterior branch of the lateral line nerve (aLLn), which has a shorter conduction time then the posterior branch. This study is the first attempt to characterize the inputs from the aLLn to the M-cell. M-cell intracellular responses to aLLn stimulation indicate a fast monosynaptic input (0.80±0.03 ms) that has a small amplitude averaging 5.85±0.42 mV. This input is bilateral and has a significantly longer latency and smaller amplitude in the contralateral M-cell. Superimposed on the evoked excitatory postsynaptic potential (EPSP) is a shunting inhibition with a delay of 1 ms, which is characteristic of other sensory inputs to the M-cell. Pharmacological manipulation and 50 Hz stimulation reveal a component of the evoked EPSP that is electrotonic, a property favoring speed of transmission. In addition, this input is localized to the lateral dendrite proximal to the inputs from the inner ear. The short latency of these inputs and their proximity to the posterior eighth nerve afferents indicate a crucial role for the aLLn in influencing the excitability and directionality of the M-cell.

Cochlear implantation in children with labyrinthine anomalies and cochlear nerve deficiency: Implications for auditory brainstem implantation

Compare outcomes among children with inner ear malformations and/or cochlear nerve deficiency (CND) who have received a cochlear implant (CI). Individual retrospective cohort study from 1993 to 2010. A select cohort of 76 children was identified. Imaging characteristics, operative findings, complications, mapping parameters, and performance were assessed. Comparisons among the different groups were undertaken. Surgery was mostly uncomplicated. Nearly all children demonstrated behavioral responses to CI stimulation irrespective of inner ear morphology or the presence of CND. Children with CND had higher pure tone averages (PTAs) and required greater charge for stimulation than other malformation types. Open-set speech perception was achieved in 100% of children with incomplete partition-enlarged vestibular aqueduct (IP-EVA), 50% of those with hypoplastic malformations, and 19% of CND cases. Robust responses on eighth nerve compound action potential (ECAP) testing through the implant was associated with higher levels of speech perception. Manually supplemented communication strategies were more common among children with hypoplastic malformations (69%) and CND (95%) than those with IP-EVA (18%). Children with IP-EVA malformations have an excellent prognosis for developing open-set speech perception and using oral communication modes following CI. On the contrary, children with severe malformations or CND may have elevated charge requirements for attaining sound detection alone. These children's prognosis for obtaining open-set speech understanding, using exclusive oral communication, and participating in mainstream education is more limited. These findings have important implications for considering alternative forms of intervention such as auditory brainstem implantation and/or supplementation with visually based communication strategies.

Seasonal plasticity of auditory hair cell frequency sensitivity correlates with plasma steroid levels in vocal fish.

Vertebrates displaying seasonal shifts in reproductive behavior provide the opportunity to investigate bidirectional plasticity in sensory function. The midshipman teleost fish exhibits steroid-dependent plasticity in frequency encoding by eighth nerve auditory afferents. In this study, evoked potentials were recorded in vivo from the saccule, the main auditory division of the inner ear of most teleosts, to test the hypothesis that males and females exhibit seasonal changes in hair cell physiology in relation to seasonal changes in plasma levels of steroids. Thresholds across the predominant frequency range of natural vocalizations were significantly less in both sexes in reproductive compared with non-reproductive conditions, with differences greatest at frequencies corresponding to call upper harmonics. A subset of non-reproductive males exhibiting an intermediate saccular phenotype had elevated testosterone levels, supporting the hypothesis that rising steroid levels induce non-reproductive to reproductive transitions in saccular physiology. We propose that elevated levels of steroids act via long-term (days to weeks) signaling pathways to upregulate ion channel expression generating higher resonant frequencies characteristic of non-mammalian auditory hair cells, thereby lowering acoustic thresholds.

Monoamine innervation of vocal and auditory circuits in the plainfin midshipman fish.

Monoamines, which include catecholamines (e.g., dopamine and noradrenaline) and serotonin, are important regulators of reward, motivation and reproductive-related behaviors across vertebrates. Studies in tetrapods have demonstrated that monoamines can also serve a modulatory function for vocalization and audition. Antibodies directed against serotonin (5-HT) and tyrosine hydroxylase (TH) (the rate limiting enzyme in catecholamine synthesis) were employed to investigate monoamine innervation of known central vocal and auditory nuclei and the sensory epithelium of the saccule, the main endorgan of hearing, in the plainfin midshipman fish, Porichthys notatus. Both 5-HT and TH-immunoreactive (-ir) terminals are abundant in hindbrain (dorsal descending octaval nucleus), midbrain (torus semicircularis), thalamic (central posterior nucleus), and ventral telencephalic auditory nuclei. In addition, very robust TH-ir is found in the octavolateralis efferent nucleus, and prominent TH-ir projections travel along the eighth nerve and terminate within the hair cell layer of the saccular epithelium. Aside from the midbrain periaqueductal gray, TH-ir is much more pronounced than 5-HT-ir throughout the descending vocal motor system, particularly in the tuberal hypothalamus and the hindbrain-spinal vocal motor nucleus, which directly innervates vocal musculature on the swimbladder. These data provide anatomical evidence that monoamines are modulators of vocal and auditory-driven behaviors in fishes.

Nonphosphorylated neurofilament protein is expressed by scattered neurons in the human vestibular brainstem

Vestibular information is critical for the maintenance of balance and posture and for the control of eye movements. The eighth nerve carries vestibular information to four brainstem nuclei called the vestibular nuclear complex (VNC); these nuclei relay vestibular signals to several additional brainstem nuclei. The structure, connections, effects of lesions and neuronal response properties of the vestibular brainstem have been studied in many nonhuman species. The development of bipedal locomotion in humans mandates differences in the vestibular control of balance and suggests that there may also be differences in the organization of the human vestibular brainstem. While the four nuclei of the VNC are described in human, there is a lot of variability among reports in their borders and extent. Further, there are several nuclei described in the human brainstem that are not present in other species. We have been using immunohistochemistry to study the patterns of expression of several different proteins to define and compare the organization of the vestibular brainstem in animals and humans. We here describe the expression of nonphosphorylated neurofilament protein (NPNFP) in the human vestibular brainstem. As in the cat, NPNFP is expressed by scattered cells within multiple regions of the vestibular brainstem and in cranial nerve nuclei. NPNFP expression in other cortical and subcortical regions suggests that it is expressed by projection neurons. For vestibular brainstem, these may be vestibulospinal, vestibulo-oculomotor or vestibulocerebellar neurons. Studies of other brain regions suggest that brainstem neurons expressing NPNFP may be especially vulnerable in different neurological disorders including Alzheimer's disease or to alterations in sensory input.

Dynamic Spike Thresholds during Synaptic Integration Preserve and Enhance Temporal Response Properties in the Avian Cochlear Nucleus

Neurons of the cochlear nuclei are anatomically and physiologically specialized to optimally encode temporal and spectral information about sound stimuli, in part for binaural auditory processing. The avian cochlear nucleus magnocellularis (NM) integrates excitatory eighth nerve inputs and depolarizing GABAergic inhibition such that temporal fidelity is enhanced across the synapse. The biophysical mechanisms of this depolarizing inhibition, and its role in temporal processing, are not fully understood. We used whole-cell electrophysiology and computational modeling to examine how subthreshold excitatory inputs are integrated and how depolarizing IPSPs affect spike thresholds and synaptic integration by chick NM neurons. We found that both depolarizing inhibition and subthreshold excitatory inputs cause voltage threshold accommodation, nonlinear temporal summation, and shunting. Inhibition caused such large changes in threshold that subthreshold excitatory inputs were followed by a refractory period. We hypothesize that these large shifts in threshold eliminate spikes to asynchronous inputs, providing a mechanism for the enhanced temporal fidelity seen across the eighth nerve/cochlear nucleus synapse. Thus, depolarizing inhibition and threshold shifting hone the temporal response properties of this system so as to enhance the temporal fidelity that is essential for auditory perception.

Otolith stimulation induces c-Fos expression in vestibular and precerebellar nuclei in cats and squirrel monkeys

Vestibular information is critical for the control of balance, posture, and eye movements. Signals from the receptors, the semicircular canals and otoliths, are carried by the eighth nerve and distributed to the four nuclei of the vestibular nuclear complex, the VNC. However, anatomical and physiological data suggest that many additional brainstem nuclei are engaged in the processing of vestibular signals and generation of motor responses. To assess the role of these structures in vestibular functions, we have used the expression of the immediate early gene c-Fos as a marker for neurons activated by stimulation of the otoliths or the semicircular canals. Excitation of the otolith organs resulted in widespread c-Fos expression in the VNC, but also in other nuclei, including the external cuneate nucleus, the postpyramidal nucleus of the raphé, the nucleus prepositus hypoglossi, the subtrigeminal nucleus, the pontine nuclei, the dorsal tegmental nucleus, the locus coeruleus, and the reticular formation. Rotations that excited the semicircular canals were much less effective in inducing c-Fos expression. The large number of brainstem nuclei that showed c-Fos expression may reflect the multiple functions of the vestibular system. Some of these neurons may be involved in sensory processing of the vestibular signals, while others provide input to the vestibulo-ocular, vestibulocollic, and vestibulospinal reflexes or mediate changes in autonomic function. The data show that otolith stimulation engages brainstem structures both within and outside of the VNC, many of which project to the cerebellum.

Evidence that the compound action potential (CAP) from the auditory nerve is a stationary potential generated across dura mater

We have investigated the generation of the compound action potential (CAP) from the auditory nerve of guinea pigs. Responses to acoustic tone-bursts were recorded from the round window (RW), throughout the cochlear fluids, from the surface of the cochlear nucleus, from the central end of the auditory nerve after removal of the cochlear nucleus, from the scalp vertex, and from the contralateral ear. Responses were compared before, during and after experimental manipulations including pharmacological blockade of the auditory nerve, section of the auditory nerve, section of the efferent nerves, removal of the cochlear nucleus, and focal cooling of the cochlear nerve and/or cochlear nucleus. Regardless of the waveform changes occurring with these manipulations, the responses were similar in waveform but inverted polarity across the internal auditory meatus. The CAP waveforms were very similar before and after removal of the cochlear nucleus, apart from transient changes that could last many minutes. This suggests that the main CAP components are generated entirely by the eighth nerve. Based on previous studies and a clear understanding of the generation of extracellular potentials, we suggest that the early components in the responses recorded from the round window, from the cochlear fluids, from the surface of the cochlear nucleus, or from the scalp are a far-field or stationary potential, generated when the circulating action currents associated with each auditory neurone encounters a high extracellular resistance as it passes through the dura mater.

Frequency tuning and intensity coding of sound in the auditory periphery of the lake sturgeon, Acipenser fulvescens

Acipenser fulvescens, the lake sturgeon, belongs to one of the few extant non-teleost ray-finned (bony) fishes. The sturgeons (family Acipenseridae) have a phylogenetic history that dates back about 250 million years. The study reported here is the first investigation of peripheral coding strategies for spectral analysis in the auditory system in a non-teleost bony fish. We used a shaker system to simulate the particle motion component of sound during electrophysiological recordings of isolated single units from the eighth nerve innervating the saccule and lagena. Background activity and response characteristics of saccular and lagenar afferents (such as thresholds, response-level functions and temporal firing) resembled the ones found in teleosts. The distribution of best frequencies also resembled data in teleosts (except for Carassius auratus, goldfish) tested with the same stimulation method. The saccule and lagena in A. fulvescens contain otoconia, in contrast to the solid otoliths found in teleosts, however, this difference in otolith structure did not appear to affect threshold, frequency tuning, intensity- or temporal responses of auditory afferents. In general, the physiological characteristics common to A. fulvescens, teleosts and land vertebrates reflect important functions of the auditory system that may have been conserved throughout the evolution of vertebrates.

Histochemical and Fluorescent Analyses of Mitochondrial Integrity in Chick Auditory Neurons following Deafferentation

Neurons rely exclusively on mitochondrial oxidative phosphorylation to meet cellular energy demands, and disruption of mitochondrial function often precipitates neuronal cell death. Auditory neurons in the chick brain stem (n. magnocellularis [NM]) receive glutamatergic innervation exclusively from ipsilateral eighth nerve afferents. Cochlea removal permanently disrupts afferent support and ultimately triggers apoptotic cell death in 30-50% of ipsilateral, deafferented neurons. Here, we evaluated whether disruption of mitochondrial function occurs during deafferentation-induced neuronal cell death. To determine whether mitochondrial dysfunction occurs preferentially within dying NM neurons. An experimental study. All birds underwent unilateral cochlea removal. Normally innervated neurons contralateral to surgery served as within-animal controls. Hatchling broiler chickens between 8 and 12 days of age served as subjects. A total of 62 birds were included in the study. Cochlea removal was performed to deafferent ipsilateral NM neurons and trigger neuronal cell death. Following unilateral cochlea removal, birds were sacrificed 12, 24, 48, or 168 hours later, and brain tissue was harvested. Brainstems were sectioned through NM and evaluated histochemically for oxidative enzyme reaction product accumulation or reacted for Mitotracker Red, an indicator of mitochondrial membrane potential (m) and cytoplasmic TdT-mediated dUTP Nick-End Labeling (TUNEL), an indicator of cell death. Histochemical staining intensities for three mitochondrial enzymes, succinate dehydrogenase (SDH), cytochrome c oxidase (CO), and ATP synthase (ATPase) were measured in individual neurons and compared in ipsilateral and contralateral NM. Comparisons were made using unpaired t-tests (CO) or Kruskal Wallis one way ANOVA followed by Dunn's post hoc pairwise comparisons (ATPase, SDH). Mitotracker Red tissue was examined qualitatively for the presence of and extent of colocalization between Mitotracker Red and TUNEL label in NM. RESULTS showed global upregulation of all three oxidative enzymes within deafferented NM neurons compared to contralateral, unperturbed NM neurons. In addition, differential SDH and ATPase staining intensities were detected across neurons within the ipsilateral nucleus, suggesting functional differences in mitochondrial metabolism across deafferented NM. Quantitative analyses revealed that deafferented neurons with preferentially elevated SDH and ATPase activities represent the subpopulation destined to die following cochlea removal. In addition, Mitotracker Red accumulated intensely within the subset of deafferented NM neurons that also exhibited cytoplasmic TdT-mediated dUTP Nick-End Labeling (TUNEL) and subsequently died. Taken together, our results demonstrate that a subset of deafferented NM neurons, presumably those that die, preferentially upregulates SDH, perhaps via the tricarboxylic acid (TCA) cycle. These same neurons undergo ATPase uncoupling and an eventual loss of Deltapsi(m).

Evidence of a Gustatory-Vestibular Pathway for Protein Transport

To demonstrate anatomically a pathway for protein transport from the palate to the vestibular system. The vestibulofacial anastomosis and associated ganglion cells were identified in a collection of 160 horizontally sectioned human temporal bones that had been stained with hematoxylin and eosin. Wheat germ agglutinin-horseradish peroxidase (HRP) was applied to the greater superficial petrosal nerve in 4 Sprague-Dawley rats. After 30 hours, the rats were killed by intracardiac perfusion, and the seventh and eighth nerves with adjacent brainstem removed. Frozen sections cut at 30 mum through this block were then reacted for HRP, counterstained with neutral red, and mounted on slides for examination in the light microscope. Thirty-two of the 160 human temporal bones contained sections through the vestibulofacial anastomosis and its ganglion. In all cases, the ganglion was incorporated into the vestibular ganglion (VG) adjacent to the nervus intermedius. In all 4 experimental rats, HRP reaction product labeled a small number of ganglion cells in the VG adjacent to the nervus intermedius and facial nerve. These observations support the presence of a pathway from receptors in the palate to the VG.

Expression of calcium‐binding proteins and nNOS in the human vestibular and precerebellar brainstem

Information about the position and movement of the head in space is coded by vestibular receptors and relayed to four nuclei that comprise the vestibular nuclear complex (VNC). Many additional brainstem nuclei are involved in the processing of vestibular information, receiving signals either directly from the eighth nerve or indirectly via projections from the VNC. In cats, squirrel monkeys, and macaque monkeys, we found neurochemically defined subdivisions within the medial vestibular nucleus (MVe) and within the functionally related nucleus prepositus hypoglossi (PrH). In humans, different studies disagree about the borders, sizes, and possible subdivisions of the vestibular brainstem. In an attempt to clarify this organization, we have begun an analysis of the neurochemical characteristics of the human using brains from the Witelson Normal Brain Collection and standard techniques for antigen retrieval and immunohistochemistry. Using antibodies to calbindin, calretinin, parvalbumin, and nitric oxide synthase, we find neurochemically defined subdivisions within the MVe similar to the subdivisions described in cats and monkeys. The neurochemical organization of PrH is different. We also find unique neurochemical profiles for several structures that suggest reclassification of nuclei. These data suggest both quantitative and qualitative differences among cats, monkeys, and humans in the organization of the vestibular brainstem. These results have important implications for the analysis of changes in that organization subsequent to aging, disease, or loss of input.