Primary Vestibular Afferents Research Articles

The Contribution of the Vertical Semicircular Canals to High-Velocity Horizontal Vestibulo-Ocular Reflex (VOR) in Normal Subjects and Patients with Unilateral Vestibular Nerve Section

We have examined to what extent the vertical semicircular canals contribute to the nonlinearity of the horizontal VOR imposed by the driving of primary vestibular afferents into inhibitory cutoff at high velocities of head rotation (Ewald's second law). The gain (eye velocity/head velocity) of the horizontal component of the VOR with the head pitched down 30 degrees and pitched up 30 degrees was examined during constant-velocity rotations in normal subjects and patients following unilateral vestibular nerve section. In normal subjects, VOR gain decreases as chair velocity increases from 60-300 degrees/s when the head is pitched up, but VOR gain remains constant when the head is pitched down. This finding implies that the mechanism by which the gain of the horizontal VOR gain remains constant at all velocities of rotation depends upon the pattern of labyrinthine stimulation. Following unilateral nerve section, we found that the directional preponderance (DP) in horizontal VOR depends upon whether the head is pitched up 30 (mean asymmetry = 5%) or pitched down 30 degrees (mean asymmetry = 20%). This is what is expected based on the degree to which the lateral and vertical semicircular canals sense horizontal head acceleration with the head in different degrees of pitch. Hence, following unilateral vestibular lesions, the DP of horizontal VOR gain is most easily elicited at high velocities of head rotation and with the head pitched down 30 degrees. Evidence for DP at the bedside using the "head-shaking nystagmus" technique may be optimally elicited with the head pitched down 30 degrees.

Vestibular compensation: role of visual motion cues in the recovery of posturo-kinetic functions in the cat

Vision has long been recognized as a sensorimotor system which plays a major role in substitution for functional deficits induced by unilateral or bilateral exclusion of primary vestibular afferents. Little is known, however, about the post-lesion influence of visual inputs on the recovery of posturo-kinetic balance in a situation where fine, well-coordinated locomotr adjustments are required. The present study was carried out in order to gain some insight into the role played by motion vision in the restoration of fine posturo-kinetic balance in adult cats subjected to unilateral vestibular neurectomy. Prior to the lesion, 15 adult animals were trained to cross a beam rotatin at various speeds. Their best global balance performance (highest beam rotation speed that did not provoke falling) and their average locomotion speed were evaluated. After the lesion, the cats were separated into three groups: (1) five animals were placed in a normal environment (animal house) (NV cats); (2) four animals were exposed to stroboscopic illumination which eliminated visual motion cues (SV cats) for 2 weeks following the lesion; and (3) three animals were placed in a normal environment and their training was interrupted for the same period as in the SV cats (NVI cats). The possible influence of the 2-week deprivation of visual motion cues on posturo-kinetic balance was also examined in three intact cats. The present behavioral study showed that: (1) early sensory deprivation caused suspension of the posturo-kinetic balance recovery process as long as it was maintained; (2) complete restoration of global balance capacities developed following the vestibular neurectomy after a significant delay in half of the SV cats; (3) the lack of motion cues resulted in severe alterations of fine posturo-kinetic balance (inappropriate dynamic motor adjustments and irregular locomotion speed regulation) in all SV cats; and (4) the visual deprivation induced a 2-week delay in the restoration of fine locomotor balance. These findings provide evidence for a defect in the visual sensory substitution processes that normally take place within the first few weeks following exclusion of primary vestibular afferents.

Vestibular and visual climbing fiber signals evoked in the uvula-nodulus of the rabbit cerebellum by natural stimulation.

1. The cerebellar uvula-nodulus receives vestibular projections from primary and secondary vestibular afferents as well as vestibularly related climbing fibers. It also receives visually related information from climbing fiber pathways. In this experiment we investigated how this information is mapped onto the uvula-nodulus. We studied the specificity, dynamics, and topographic distribution of climbing fiber responses (CFRs), simple spike responses, and mossy fiber terminal responses evoked by vestibular and optokinetic stimulation in rabbits anesthetized with alpha-chloralose. 2. Vestibularly evoked CFRs were found in the ventral uvula and nodulus. These responses were evoked during static roll tilt of the rabbit about a longitudinal axis and by sinusoidal oscillation about the longitudinal axis. Purely static responses were attributed to stimulation of the utricular otolith by the linear acceleration of gravity. CFRs that lacked a static component were attributed to activation of the semicircular canals. 3. Using a "null technique" we showed that the canal-sensitive CFRs were caused by stimulation of the anterior or posterior semicircular canals. Of the CFRs classified as canal related, 96% could be attributed to stimulation of the vertical semicircular canals. 4. Increases in CFRs were correlated with decreases in simple spike responses in half the Purkinje cells from which we recorded. These climbing-fiber-induced pauses in simple spikes occurred during spontaneous climbing fiber discharge as well as during climbing fiber discharge evoked by vestibular stimulation. The duration of this pause was inversely proportional to the spontaneous level of simple spikes before the occurrence of a CFR. In the other half of the recorded population of Purkinje cells, vestibularly driven CFRs did not alter the simple spike responses. 5. Vestibularly and visually mediated CFRs were topographically represented on the surface of the uvula-nodulus. CFRs driven by ipsilateral otolithic inputs were distributed over the entire mediolateral surface of the uvula-nodulus. CFRs driven by the ipsilateral posterior semicircular canal were distributed in a sagittal strip approximately 1.5 mm wide, extending laterally from the midline of the nodulus. CFRs driven exclusively by horizontal, posterior-->anterior optokinetic stimulation of the ipsilateral eye were distributed in a sagittal strip approximately 0.5 mm wide located 0.5-1.0 mm from the midline and restricted to the ventral nodulus. CFRs driven by the ipsilateral anterior semicircular canal were found in a sagittal strip approximately 1.0 mm wide extending 1.0-2.0 mm from the midline. 6. The sagittal, topographically arrayed climbing fiber strips effectively map a mediolateral gradient of possible postural responses based on vestibular and optokinetic information.

The role of GABA in NMDA-dependent long term depression (LTD) of rat medial vestibular nuclei

The role of GABA in NMDA-dependent long term depression (LTD) in the medial vestibular nuclei (MVN) was studied on rat brainstem slices. High frequency stimulation (HFS) of the primary vestibular afferents induces a long lasting reduction of the polysynaptic (N2) component of the field potentials recorded in the dorsal portion of the MVN. The induction but not the maintenance of this depression was abolished by AP5, a specific blocking agent for glutamate NMDA receptors. The involvement of GABA in mediating the depression was checked by applying the GABA A and GABA B receptor antagonists, bicuculline and saclofen, before and after HFS. Under bicuculline and saclofen perfusion, HFS provoked a slight potentiation of the N2 wave, while the N2 depression clearly emerged after drug wash-out. this indicates that GABA is not involved in inducing the long term effect, but it is necessary for its expression. Similarly, the LTD reversed and a slight potentiation appeared when both drugs were administered after its induction. Most of these effects were due to the bicuculline, suggesting that GABA A receptors contribute to LTD more than GABA B do. According to our results, it is unlikely that the long lasting vestibular depression is the result of a homosynaptic LTD. On the contrary, our findings suggest that the depression is due to an enhancement of the GABA inhibitory effect, caused by an HFS dependent increase in gabaergic interneuron activity, which resets vestibular neuron excitability at a lower level.

Differences in the brain stem terminations of large- and small-diameter vestibular primary afferents

1. We visualized the central axons of 32 vestibular afferents from the posterior canal by extracellular application of horseradish peroxidase, reconstructed them in three dimensions, and quantified their morphology. Here we compare the descending limbs of central axons that differ in parent axon diameter. 2. The brain stem distribution of descending limb terminals (collaterals and associated varicosities) varies systematically with parent axon diameter. Large-diameter afferents concentrate their terminals in rostral regions of the medial/descending nuclei. As axon diameter decreases, there is a significant shift of terminal concentration toward the caudal vestibular complex and adjacent brain stem. 3. Rostral and caudal regions of the medial/descending nuclei have different labyrinthine, cerebellar, intrinsic, commissural, and spinal connections; they are believed to play different roles in head movement control. Our data help clarify the functions of large- and small-diameter afferents by showing that they contribute differentially to rostral and caudal vestibular complex.

Gaba mediated long-term depression (LTD) in the rat medial vestibular nuclei.

As previously demonstrated, high frequency stimulation (HFS) of the primary vestibular afferents always induces a clear, long lasting depression of the polysynaptic (N2) component of the field potentials recorded in the dorsal portion of the medial vestibular nuclei (MVN). The induction of the HFS effect was mediated by the activation of glutamate NMDA receptors, since it was blocked by AP5. The mechanisms at the basis of such a depression were studied. Our results demonstrate that Gaba, acting on both GabaA and GabaB receptors, is involved in mediating this phenomenon. In fact, HFS applied during Bicuculline and Saclofen perfusion, was no longer able to induce an N2 depression, but provoked a slight potentiation. However, the N2 depression clearly emerged after drug wash-out. Furthermore, Bicuculline and Saclofen fully abolished the N2 depression and highlighted the potentiation, when administered after HFS. The possibility that the N2 depression is the result of a homosynaptic LTD can be excluded on the basis of our results. On the contrary, our findings suggest that the depression is due to an enhancement of the Gaba inhibitory effect due to an HFS dependent increase in gabaergic interneuron activity, which resets vestibular neuron excitability at a lower level.

Expression of Substance P, CGRP, and GABA in the Vestibular Periphery, With Special Reference to Species Differences

The present study was conducted to elucidate species differences in the distribution of neuroactive substances, including substance P (SP), calcitonin gene-related peptide (CGRP) and gamma-aminobutyric acid (GABA), in the vestibular periphery of various animals (chicken, pigeon, rat, guinea pig and squirrel monkey). SP-like immunoreactivity was found in a subset of the primary vestibular afferents with no marked species differences in the staining pattern. In contrast, the localization of CGRP- and GABA-like immunoreactivities in the efferent nerve fibers varied according to species. This difference in the distribution pattern of neuroactive substances, found in the efferent system, may indicate that each species has a chemically (and probably functionally) distinct efferent system which is related to its specific environment and/or evolution.

Synchronous bursting in a subset of interneurons inhibitory to the goldfish Mauthner cell: synaptic mediation and plasticity.

1. Presynaptic activity in the inhibitory network impinging on the Mauthner (M-) cell was investigated in the goldfish medulla in vivo using extra- and intracellular recordings. The inhibitory presynaptic volley elicited by stimulation of the contralateral vestibular nerve consisted of multiple successive peaks at high frequency (up to 1,000 Hz). Less pronounced multicomponent responses were recorded after antidromic activation of the M-cell. Such high-frequency "oscillatory" field potentials also occurred spontaneously. 2. In intracellular recordings, a subset of inhibitory interneurons showed evoked and spontaneous burst discharge. Burst action potentials were correlated with the peaks in the extracellular volley, suggesting that repetitive firing of these cells is synchronized. Nonbursting cells, on the other hand, fired single action potentials in response to vestibular stimuli and were not activated via the M-cell collateral network. 3. Bursting cells were determined morphologically to be part of the feedback inhibitory circuit. Their responses to stimulation of the contralateral vestibular nerve thus suggest the existence of a crossed excitatory pathway to these interneurons. 4. Vestibular-evoked excitatory postsynaptic potentials (EPSPs) in bursting interneurons had a short latency of 0.781 +/- 0.08 ms (mean +/- SD, n = 18) but reached threshold at 2.25 +/- 1 ms (n = 21). These characteristics are suggestive of a chemically mediated EPSP. Indeed, the evoked synchronous repetitive activity of these cells was prevented by superfusion with excitatory amino-acid receptor antagonists. 5. Bursting neurons showed several characteristics that differentiate them from nonbursting cells, including brief action potentials, plateau responses, and intense spontaneous subthreshold activity. 6. With extracellular recordings, tetanization of contralateral vestibular primary afferents evoked a long-lasting potentiation of oscillatory population responses in 11 of 27 cases. Furthermore in three experiments, the frequency of occurrence of spontaneous bursts was enhanced and a similar facilitation was detected at the intracellular level. 7. We conclude that a subset of interneurons in this inhibitory network is capable of repetitive discharges and that evoked as well as spontaneous firing in this population is synchronized. Although electrical coupling between interneurons may mediate synchronization and intrinsic membrane properties may promote burst activity, our data suggest strongly that repetitive firing requires chemically mediated transmission. Furthermore they indicate that the mechanisms underlying evoked as well as spontaneous bursting in this population show activity-dependent plasticity.

Functional architecture of vestibular primary afferents from the posterior semicircular canal of a turtle, Pseudemys (Trachemys) scripta elegans

Physiological studies in many vertebrates indicate that vestibular primary afferents are not a homogeneous population. Such data raise the question of what structural mechanisms underlie these physiological differences and what functional role is played by afferents of each type. We have begun to answer these questions by characterizing the architecture of 110 afferents innervating the posterior canal of Pseudemys scripta. We emphasize their spatial organization because experimental evidence suggests that afferent physiological properties exhibit significant spatial heterogeneity. The sensory surface of the posterior canal comprises paired, triangular hemicristae, which are innervated by two afferent types. Bouton afferents (66% of total afferents) are found over the entire sensory surface. They differ significantly in the shape and size of their collecting areas, number of boutons, soma size, and axon diameter; this morphological variation is systematically related to the afferent's spatial position. In addition, multivariate analyses suggest that bouton afferents may comprise two subtypes: alpha afferents have delicate processes and are found throughout the crista; beta afferents are more robust and are concentrated preferentially toward the canal center. Calyx-bearing afferents comprise two morphological subtypes: dimorphs (13% of total afferents) bear calyceal and bouton endings; calyceal afferents (21%) bear calyceal endings only. Both types occur exclusively in an elliptical region near the center of each hemicrista; their morphology varies with radial distance from the center of this elliptical region. Our data provide evidence that in Pseudemys: (1) the classical vestibular afferent types (bouton, calyx, dimorph) are structurally heterogeneous, and (2) their spatial sampling characteristics are highly structured and distinctive for each type. These spatial patterns may shed light on regional differences in physiological profiles of vestibular afferents, and they raise questions about the role of this spatial heterogeneity in signaling head movement.

Physiological properties of vestibular primary afferents that mediate motor learning and normal performance of the vestibulo-ocular reflex in monkeys

We have used electrical stimulation of the vestibular apparatus to reveal parallels between the physiological responses of the vestibular afferents activated at different currents and the properties of the evoked eye movements before and after magnifying spectacles had been used to cause motor learning in the vestibulo-ocular reflex (VOR). Stimulation with the lowest currents caused little or no eye motion, but activated all the afferents with irregular spontaneous discharge, low sensitivities to head velocity, and highly phasic responses during rapid head turns. Stimulation with moderate currents caused substantial eye motion that was weakly affected by motor learning; these currents activated afferents with a wide range of physiological properties, including many that had intermediate discharge regularity, high sensitivity to head velocity, and clear phasic responses during rapid head turns. Stimulation at still higher currents caused still larger eye movements that were strongly altered by motor learning; these currents activated primarily afferents that had regular spontaneous discharge, lower sensitivities to head velocity, and tonic responses during rapid head turns. Stimulation at the highest currents did not cause any further increment in the amplitude of the evoked eye movement, but activated the afferents with the most regular spontaneous discharge and the lowest sensitivities to head velocity. The data imply that the VOR pathways receive substantial vestibular inputs from afferents with a middle range of thresholds for electrical stimulation. These afferents have a wide range of physiological properties, including a large group that shows substantial phasic responses during rapid head turns. The data also suggest that only a subset of these afferents, primarily those with more regular spontaneous discharge, project into the VOR pathways that are modified in association with motor learning.

Morphological correlations between spontaneously discharging primary vestibular afferents and vestibular nucleus neurons in the cat.

Synaptic connections between physiologically classified primary vestibular afferents (PVAs) and their target vestibular nucleus (VN) neurons were examined by a combination of intra-axonal staining and electron microscopic techniques. PVAs originating from the horizontal semicircular canal were electrophysiologically classified as either regular- or irregular-type based on the regularity of their spontaneous discharge patterns, and were intra-axonally labeled with horseradish peroxidase (HRP). HRP-labeled PVAs of both types had many swellings along their course that contacted VN neurons. These swellings contained spherical synaptic vesicles and showed asymmetric postsynaptic specialization. Target VN neurons of both types of PVAs were distributed primarily in the superior, medial, and inferior VN. Irregular-type PVAs made more axosomatic contacts than did regular-type PVAs. The soma size of target VN neurons and the number of terminal boutons per target VN neuron were larger for irregular-type PVAs than for regular-type PVAs. Large VN neurons (presumably kinetic neurons) were innervated exclusively by irregular-type PVAs. Small VN neurons were innervated by PVAs of the regular-type and the irregular-type. These results demonstrate that there is a correlation between the physiological properties and morphological characteristics of PVAs and their target VN neurons.

NMDA receptor-mediated long term modulation of electrically evoked field potentials in the rat medial vestibular nuclei.

The effect of high frequency stimulation (HFS) of the primary vestibular afferents on field potentials recorded in the ipsilateral Medial Vestibular Nuclei (MVN) was studied. Our results show that potentiation and depression can be induced in different portions of MVN, which are distinguishable by their anatomical organization. HFS induces potentiation of the monosynaptic component in the ventral portion of the MVN, whereas it provokes depression of the polysynaptic component in the dorsal portion of the same nucleus. The induction of both potentiation and depression was blocked under AP5 perfusion, thus demonstrating that NMDA receptor activation mediates both phenomena. Furthermore, the finding that the field potentials were not modified during perfusion with DL-AP5, as previously reported, supports the hypothesis that NMDA receptors are not involved in the normal synaptic transmission from the primary vestibular afferent fibres, but are only activated following hyperstimulation of this afferent system. Our results suggest that the mechanisms of long term modification of synaptic efficacy observed in MVN may underlie the plasticity phenomena occurring in vestibular nuclei.

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)

Postnatal developmental changes in the responses of mouse primary vestibular neurons to externally applied galvanic currents

The ontogenesis of vestibular primary neuron sensitivity to depolarisation produced by galvanic current stimulations was studied in mouse inner ear explants maintained in vitro. Cathodal galvanic stimulations, which elicit an increase of the discharge frequencies, are assumed to act on the spike initiation site by depolarizing the neuron. The responses of neurons to galvanic currents at various developmental stages were recorded. The pattern of responses reflected the sensitivities of the neurons to depolarization. At birth, about 75% of the vestibular neurons responded weakly to high intensity galvanic currents thus indicating that they were able to generate action potentials. However, the very low gain of the response to the stimulation revealed the immaturity of the neurons at the spike generation site. Between the day of birth and the ninth postnatal day, an increase in the gain of the responses was observed, indicating the enhancement of the sensitivity of the vestibular neurons to the galvanic currents. This increase in sensitivity was more pronounced from the fourth postnatal day. The response of the neurons to galvanic stimulation increased gradually during postnatal development without reaching a plateau at postnatal day 9 indicating that a further physiological maturation occurs after this stage. These results are consistent with the morphological maturation of the vestibular primary afferents and with previous studies showing that the physiological maturation parallels myelination of the afferent fibers.

The origin of high and regular discharge rates of eye-movement-related neurons in the region of the interstitial nucleus of Cajal

Burst-tonic neurons in the region of the interstitial nucleus of Cajal (INC) that show a close correlation to vertical eye movement have been known to exhibit high and regular discharge rates, not only during fixation in alert animals, but also during sleep. Since they receive major input from vertical semicircular canals, we examined in this study whether or not the source of the high and regular discharge rates was the primary vestibular afferents. Infusion of lidocaine into the middle ear bilaterally resulted in a significant decrease of mean discharge rates and an increase in the coefficient of variation of the mean rates. However, burst-tonic neurons in cats that had received bilateral labyrinthectomy 6 weeks previously still exhibited high and regular discharge rates similar to those of normal cats. These results indicate that high and regular discharges of eye-position-related INC cells are maintained largely by input from primary vestibular afferents in normal cats. However, such characteristic discharges could also be maintained centrally in the brainstem without peripheral vestibular input in labyrinthectomized cats.

Ultrastructural evidence that early synapse formation on central vestibular sensory neurons is independent of peripheral vestibular influences

Migration and early differentiation of neurons of the tangential vestibular nucleus of the chick take place between embryonic days 5 and 8. In the absence of primary vestibular afferents (otocyst-ablation), a previous light microscope study documented that early developmental events still occurred, but the neurons failed to complete differentiation and to survive. In order to understand why these neurons undergo normal early development, we have repeated the vestibular deafferentation paradigm followed by ultrastructural observations on these neurons. We found that the ultrastructural events associated with migration and differentiation in the deafferented tangential nucleus were essentially normal from 5 to 8 days. Most important, longitudinal fibers, presumably of central, nonvestibular origins, formed the first synapses at the same time and sequence as observed in normal embryos. Thus vestibular sensory neurons receive their first input from central fibers, initiating events in the formation of a central vestibular circuitry without the influence of peripheral vestibular fibers or endorgan.

Morphophysiology of synaptic transmission between type I hair cells and vestibular primary afferents. An intracellular study employing horseradish peroxidase in the lizard, Calotes versicolor

Intracellular records with glass microelectrodes filled with horseradish peroxidase (HRP) were taken from primary afferents of the horizontal semicircular canal in the lizard, Calotes versicolor. A coefficient of variation (CV) of the interspike intervals of spontaneous action potentials (APs) was calculated and correlated with the terminal morphologies of afferents within the canal crista. Irregular fibers with CV > 0.4 always correlated with a nerve chalice or calyx afferent terminal expansion surrounding one or more type I hair cells; more regular fibers with CV < 0.4 always correlated with a dimorphic or bouton only terminal expansion of afferents. Afferents with a CV > 0.4 demonstrated miniature excitatory postsynaptic potentials (mEPSPs) that summated to initiate APs. APs were blocked by tetrodotoxin and mEPSP frequency was modulated by caloric stimulation. Cobalt application reversibly blocked mEPSPs. Electron microscopic examination of physiologically studied afferents with CV > 0.4 revealed synaptic profiles consisting of typical synaptic bodies and synaptic vesicles in the type I hair cell presynaptic to the nerve chalice. Examples of the interspike baseline in regular and irregular afferents suggest differential modes of impulse initiation in these two fiber types.

The electrically evoked vestibulo‐ocular reflex: I. normal subjects

Recent animal studies indicate that electric currents applied through perilymphatic-space electrodes stimulate vestibular primary afferent neurons directly. These findings suggest that electrical stimulation may provide a testing method by which the vestibular nerve and central pathways could be evaluated separately from the vestibular end-organ. The goal of this study was to obtain normative data on human beings for an electrically evoked vestibulo-ocular reflex (EVOR). Sinusoidal electrical stimuli (0.0125 to 0.8 Hz, 4 mA peak intensity) were applied along the interaural axis through mastoid electrodes in 10 subjects. Horizontal eye movements were recorded by an infrared limbus-tracking device. The subjects also underwent rotational stimulation at the same frequencies so that their horizontal vestibulo-ocular reflex (VOR) could be evaluated. Nystagmus was observed in the EVOR at lower stimulus frequencies, whereas purely sinusoidal eye deviations occurred at higher frequencies. The phase of the EVOR slow-component eye velocity consistently lagged the stimulus. This contrasts with the phase measurements of the VOR in the same subjects, which exhibited a lead relative to head velocity. These findings suggest that currents applied to human beings may activate vestibular primary afferents independent of peripheral receptor mechanisms and thereby provide a "site-of-lesion" testing method by which the vestibular nerve and central pathways can be evaluated separately from the vestibular end-organ.

NMDA receptors contribute to the resting discharge of vestibular neurons in the normal and hemilabyrinthectomized guinea pig

Excitatory amino acids (EAA) like L-Glutamate or L-Aspartate have been suggested to be the neurotransmitters at the synapses between primary vestibular afferents and second-order vestibular neurons. In the first part of our work, we have tested the possibility that EAA receptors are implicated in the control of posture by vestibular nuclei. Normal guinea pigs were implanted with minipumps delivering EAA antagonists in the vestibular nuclei. Their resting posture was monitored during the perfusion by using an X-ray photographic method. Chronic infusion of D-L-2-amino-5-phosphonovaleric acid (APV), a specific antagonist of NMDA receptors, in the vestibular nuclei induced a postural and oculomotor syndrome similar to the one observed following acute vestibular deafferentation. Administration of 6-cyano-7-nitro-quinoxaline-2-3-dione (CNQX), a specific antagonist of kainate and quisqualate receptors, failed to induce any postural syndrome or eye deviation. These results suggest that, under physiological conditions, N-methyl-D-aspartate (NMDA) receptors, contrary to kainate and quisqualate receptors, are essential for the maintenance of a symmetric posture and of a normal eye position at rest. Previous electrophysiological studies have demonstrated that following unilateral labyrinthectomy the recovery of a resting discharge in the deafferented vestibular nuclei plays a key role in the compensation of postural disorders. In the second part of this study, we have tested whether NMDA receptors could be implicated in this postural recovery. APV mini-pumps were implanted in hemilabyrinthectomized guinea pigs after complete compensation. A postural decompensation was induced, which occurred after delivery of the same amount of APV which provoked a vestibular syndrome in intact guinea pigs.(ABSTRACT TRUNCATED AT 250 WORDS)

Ultrastructural study of synapses at the time of neuronal migration and early differentiation in the tangential vestibular nucleus of the chick embryo in vivo

The chick tangential nucleus is a primary vestibular nucleus whose two main neuron types migrate and begin to differentiate between 5 and 8 days in the embryo (gestation takes 20-21 days). Based on rapid Golgi impregnations of developing tangential neurons and growing fibers, we have identified ultrastructural counterparts and characterized interactions in the nucleus from 5 to 8 days. Developing tangential neurons received the earliest synapses at 5 days on their primitive processes and subsequently on their cell bodies by longitudinal fibers of unknown origins. In contrast, the primary vestibular afferents did not form identified synapses on the developing tangential neurons until 7 1/2 days. In conclusion, the earliest synapses in the tangential nucleus are formed by longitudinal fibers, which are probably not primary vestibular afferents. Since a specific class of fibers forms particular synapses on the tangential neuron precursors at predictable times prior to and during neuronal migration and also at the onset of differentiation, the role of these synapses in developmental events should be explored.