Passive activation of neck proprioceptive inputs does not influence the discharge patterns of vestibular nuclei neurons.
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Responses of cortical vestibular center produced by stimulation of vestibular nuclei and visual association area in the cat.
(1) The cortical projection of the vestibular nuclei (LVN, MVN and IVN) was investigated by the evoked potential and unit discharge analyses in the cat anesthetized with alpha-chloralose and/or immobilized with gallamine triethiodide. (2) This projection field coincided well with that of the vestibular nerves, being principally contralateral by LVN stimulation but nearly symmetrical by either MVN or IVN stimulation. (3) Of 11 units responsive to vestibular nuclei stimulation, 6 reacted to stimulation of the visual association cortex (anterior part of the Clare-Bishop area). The response pattern of the cortical vestibular units by C-B stimulation was a sequence of excitation, inhibition and rebound. (4) Interaction of visual information with the cortical vestibular neurons was discussed.
Animals↗
Cat vestibular nuclear neuron responses to active head rotations.
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Animals↗
Effects of serotonin, GABA and glycine on the activity of pause neurons during vestibular nystagmus in the cat.
Pause neurons (PNs), found in the pontine raphe nuclei, are important in the regulation of fast eye movements. The present study focuses on transmitters regulating the activity of the PNs. Extracellular spikes of single PNs and ocular motor nerve discharges were simultaneously recorded during horizontal vestibular nystagmus in the alert cat. Several transmitter candidates were iontophoretically applied, while methysergide, a serotonin antagonist, was administered both systemically and topically. The following data supported the conclusion that PNs are probably under the control of two different types of neurons, and the firing of PNs may be caused partly by GABAergic, but not by glycinergic neurons: 1) serotonin markedly decreased the spontaneous firing of the PNs; 2) methysergide abolished the inhibitory effect of serotonin on the PN firing; however, a pause pattern was maintained under this condition; 3) GABA moderately suppressed the firing but only in 25% of PNs; and 4) glycine hardly changed the PN firing in any case examined.
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Inputs from regularly and irregularly discharging vestibular nerve afferents to secondary neurons in the vestibular nuclei of the squirrel monkey. II. Correlation with output pathways of secondary neurons.
1. Intracellular recordings were made from secondary neurons in the vestibular nuclei of barbiturate-anesthetized squirrel monkeys. Monosynaptic excitatory postsynaptic potentials (EPSPs) evoked by stimulation of the ipsilateral vestibular nerve (Vi) were measured. An electrophysiological paradigm, described in the preceding paper (26), was used to determine the proportion of irregularly (I) and regularly (R) discharging Vi afferents making direct connections with individual secondary neurons. The results were expressed as a % I index, an estimate for each neuron of the percentage of the total Vi monosynaptic input that was derived from I afferents. The secondary neurons were also classified as I, R, or M cells, depending on whether they received their direct Vi inputs predominantly from I or R afferents or else from a mixture (M) of both kinds of Vi fibers. The neurons were located in the superior vestibular nucleus (SVN) or in the rostral parts of the medical or lateral (LVN) vestibular nuclei. 2. Antidromic activation or reconstruction of axonal trajectories after intrasomatic injection of horseradish peroxidase (HRP) was used to identify three classes of secondary neurons in terms of their output pathways: 1) cerebellar-projecting (Fl) cells innervating the flocculus (n = 26); 2) rostrally projecting (Oc) cells whose axons ascended toward the oculomotor (IIIrd) nucleus (n = 27); and 3) caudally projecting (Sp) cells with axons descending toward the spinal cord (n = 13). Two additional neurons, out of 21 tested, could be antidromically activated both from the level of the IIIrd nucleus and from the spinal cord. 3. The Vi inputs to the various classes of relay neurons differed. As a class, Oc neurons received the most regular inputs. Sp neurons had more irregular inputs. Fl neurons were heterogeneous with similar numbers of R, M, and I neurons. The mean values (+/- SD) of the % I index for the Oc, Fl, and Sp neurons were 34.7 +/- 24.7, 51.9 +/- 30.4, and 61.8 +/- 18.0%, respectively. Only the Oc neurons had a % I index that was similar to the proportion of I afferents (34%) in the vestibular nerve (cf. Ref. 26). 4. The commissural inputs from the contralateral vestibular nerve (Vc) also differed for the three projection classes. Commissural inhibition was most common in Fl cells: 22/25 (88%) of the neurons had Vc inhibitory postsynaptic potentials (IPSPs) and 1/25 (4%) had a Vc EPSP. In contrast, Vc inputs were only observed in approximately half the Oc and Sp neurons.(ABSTRACT TRUNCATED AT 400 WORDS)
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Effects of baclofen on medial vestibular nucleus neurones in guinea-pig brainstem slices.
Using intracellular recordings of medial vestibular nucleus neurones (MVNn) in guinea-pig brainstem slices, the effects of baclofen, a specific agonist of the metabotropic GABAB receptors, were tested on the three main types of MVNn (A, B and B + LTS MVNn) that were previously identified in this nucleus. Regardless of their type, almost all MVNn were hyperpolarized and inhibited by baclofen. These hyperpolarizing effects persisted following either the addition of tetrodotoxin (TTX) in the perfusion medium, or in the presence of a high Mg2+/low Ca2+ solution known to block synaptic transmission. These results demonstrate that all types of MVNn are endowed with postsynaptic GABAB receptors.
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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)
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[Calcitonin gene-related peptide changes in efferent vestibular system during vestibular compensation].
OBJECTIVE: To investigate the calcitonin gene-related peptide (CGRP) effect on efferent vestibular system during pathological state of vestibular afferent system. METHODS: An animal model of vestibular compensation was made by administration of streptomycin to rat vestibular organ to destroy unilateral vestibular function. Change of CGRP in efferent vestibular neurons in all processes from vestibular disorder to vestibular compensation was observed utilizing ABC method of immunohistochemical technique. RESULTS: Efferent vestibular neurons of normal animals showed low immunoreactivity to CGRP. The number of CGRP immunoreactivity neurons and level of CGRP immunoreactivity increased in efferent vestibular system during vestibular disorder, and these changes decreased with vestibular compensation. CONCLUSION: Activity of CGRP in efferent vestibular system plays a regular role on accelerating vestibular compensation.
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Abnormalities of the stapedius reflex in patients with vertigo.
Analysis of the latency, amplitude, and rise characteristics of the stapedius reflex as demonstrated on a strip recorder revealed abnormalities in patients with vestibular neuronitis and other vertigo syndromes. The findings in vestibular neuronitis, acute labyrinthitis, perilymphatic fistulas, Meniere's disease, cerebrovascular insufficiency, and metabolic vertigo are described. Alterations in the stapedius reflex included increase in latency, decrease in amplitude, stepping of the rise, and absence of the reflex. This study suggests that absence of the reflex can be associated with vertigo as well as with acoustic neuromas and other retrocochlear lesions. The findings of abnormalities in vestibular neuronitis support a brain-stem localization as the site of lesion in this disease.
Cerebrovascular Disorders↗
Responses of flocculus and vestibular nuclei neurons in Weaver mutant mice (B6CBA wv/wv) to combined head and body rotation.
The responses of vestibular nuclei (Vn) neurons and floccular Purkinje (P) cells to natural stimulation of the horizontal canals were recorded in paralyzed Weaver mutant mice. The Weaver mice suffer from an almost complete postnatal degeneration of granule cells and a portion of the P cells (Sidman et al. 1965). Parallel fibers are never elaborated (Bradley and Berry 1978). Recording sites were localized by means of small, iontophoretically applied HRP markings. Phase and sensitivity were analyzed by a Fourier analysis and a "best sine fitting" program. As in the normal "control" mice (Grüsser-Cornehls et al. 1995), the "simple spike" discharges of Vn and P cells in Weaver mutant mice are modulated sinusoidally upon sinusoidal stimulation. The neuronal response amplitude at fundamental frequency (determined from peristimulus time histograms, PSTHs increased with frequency (0.05-0.5 Hz) for both Vn and floccular neurons. The stimulus frequency/response amplitude and sensitivity (re velocity) curves for floccular neurons are distinctly lower in magnitude than those of Vn neurons (P < 0.01). In our sample of neurons, the Vn neurons curves of the mutants display a remarkable be behavior: the mean value curve of type I neurons is shifted upward, indicating a loss of inhibition but that of type II, downward, demonstrating a downregulation in comparison with the control values. The difference between the two curves is statistically significant (P < 0.001). The mean value curve of all mutant Vn neurons depends on the different fractions of type I and type II neurons in the sample investigated. In our investigations, the mean value curves of both type I and type II neurons also exceed those of the normal controls. The phase shift relative to head angular velocity in the midfrequency range in Vn neurons was very similar to that in normal controls, but the phase advance in the range of 0.3-0.5 Hz was somewhat larger and the SD larger over the whole range tested. Concerning the phase relationship for floccular neurons, a major difference occurred in contrast to the normal controls: the phase lead and phase lag varied from neurons to neuron, in individual neurons from frequency to frequency, and in some neurons distinctly from trial to trail. It is hypothesized that an intact mossy fiber-granule cell-parallel fiber system plays an important role in an orderly information flow, transmitted through the P-cell axons, and that the morphological disruption has implications for target cell activity. There is a strong suggestion that the diverse behavior of type I and type II neurons in the Vn may have implications for the poor motor performance in Weaver mutant mice.
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Excitatory effects of 5-hydroxytryptamine on the medial vestibular nuclear neuron via the 5-HT2 receptor.
This study was designed to investigate the mechanisms of action of the 5-HT2 receptor on the spontaneous electrical activity and potassium currents of the rat medial vestibular nuclear neurons using whole-cell patch clamp recordings. The spike width of spontaneous action potential was not affected by 5-alpha-methylhydroxytryptamine. The spike frequency and resting membrane potential was increased by 5-alpha-methylhydroxytryptamine. The amplitude of afterhyperpolarization was decreased by 5-alpha-methylhydroxy-tryptamine. The peak current of the potassium currents of the neuron treated with 5-alpha-methylhydroxytryptamine was decreased. After blockade of calcium-dependent potassium currents, 5-alpha-methylhydroxytryptamine did not inhibit potassium currents. These results suggest 5-alpha-methylhydroxytryptamine increases spontaneous firing of the medial vestibular nuclear neurons by inhibiting calcium dependent potassium currents.
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Pathways mediating optokinetic responses of vestibular nucleus neurons in the rat.
1. The effects of various brain lesions on the responses of vestibular nuclear neurons (Vn) of the horizontal semicircular canal system to optokinetic stimulations were studied to elucidate the optokinetic path from the retina to the vestibular nuclei. A previous study performed in intact rats served as a control [2]. 2. It was shown that the pretectal region including the n. of the optic tract is the first central relay in the optokinetic path; it receives its functionally effective input from the contralateral eye. Unilateral lesions of this area rendered all Vn responses unidirectional when tested with binocular stimulation. Lesions of other visual centers such as the superior colliculi or visual cortices had no influence on the optokinetic response properties of Vn. 3. The area of the n. reticularis tegmenti pontis (NRTP) proved to be an important link between pretectum and vestibular nuclei: Unilateral lesions produced effects similar to those described for pretectal lesions. Pretectal axons to NRTP descend lateral to the MLF and tectospinal tract. 4. It was demonstrated that the vestibular commissure plays the crucial role in mediating the mirror image optokinetic effects to Vn on the opposite side and assures the bidirectionality of the responses to binocular stimulation. 5. Cerebellectomy did not significantly affect the Vn responses to the optokinetic stimuli presented in this study. 6. Electrical stimulation of the pretectum excited type II and inhibited type I Vn ipsilaterally and had the opposite effect on Vn located on the opposite side. NRTP stimulation excited type II and inhibited type I ipsilaterally; latency analysis of these effects suggested that the pretectal stimuli excited opsilateral NRTP neurons which, in turn, excited ipsilateral type II Vn. Ipsilateral type I inhibition as well as the concurrent contralateral type II inhibition and type I excitation are produced by the inhibitory action of type II on type I and the commisural system. 7. Systemic application of picrotoxin abolished all optokinetic responses of Vn except the type II activation. This finding further supports the hypothesis described above. 8. Unilateral pretectal or NRTP lesions abolished OKN to surround motion in the direction of the lesion.
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Positional test in acute vestibular disorders.
With the aid of th positiogram, a quantitative recording of th positional test, it was possible to study the intensity of nystagmus in three acute vestibular diseases (vestibular neuronitis, Meniere's disease and sudden hearing loss with vestibular involvement). Patients with vestibular neuronitis in the acute stage showed a higher intensity of nystagmus during the positional test than patients passing through the irritation stage of Menière's disease. Especially patients suffering from vestibular neuronitis complained also subjectively about such an intense vertigo that they were seized by a feeling of annihilation at the onset of the disease. Quantification of the nystagmus during the positional test allows the progress, constancy or remission of the findings to be identified during the follow-up checks. Protracted constant pathological results obtained during the positional test, or when they become progressive, constitute in the light of our experience an indication for neuroradiological clarification in order to rule out an acoustic neurinoma as a cause (especially when a unilateral sensorineural hearing impairment exists).
Aged↗
Enhancement of GABA-mediated inhibition of rat medial vestibular nucleus neurons by the neurosteroid 20-hydroxyecdysone.
In vivo electrophysiological and patch-clamp studies were performed to determine whether 20-hydroxyecdysone (20-HE), a neurosteroid, influenced neuronal activities of the medial vestibular nucleus (MVN) using chloral hydrate-anesthetized rats and dissociated MVN neurons, respectively. Single neuronal activities of MVN were extracellularly recorded with a glass-insulated silver wire microelectrode attached along a seven-barreled micropipette. Each micropipette was filled with 20-HE, glutamate, bicuculline or 2 M NaCl. These chemicals were applied microiontophoretically to the immediate vicinity of the target neurons. Microiontophoretically applied 20-HE (20-80 nA) dose-dependently decreased rotation-induced firings of both type I and II neurons, which were identified according to their responses to horizontal sinusoidal rotations. Microiontophoretically applied bicuculline, a GABAA receptor antagonist, inhibited 20-HE-induced decreases in neuronal firing of MVN. These findings suggest that 20-HE potentiates the action of GABA, probably by acting directly on the GABAA receptor of MVN neurons. In addition, microiontophoretically applied 20-HE decreased firings induced by glutamate in both type I and II neurons. This decrease by 20-HE was also antagonized with bicuculline. Furthermore, the effects of 20-HE on GABA-induced currents in acutely dissociated MVN neurons were investigated using the whole-cell patch-clamp technique. Under voltage-clamp conditions, GABA (10 microM)-induced currents were potentiated in the presence of 20-HE (100 microM). These findings suggest that 20-HE inhibits MVN neurons by acting on the modulatory site on GABA receptor-ion channel complexes to potentiate GABA inhibition.
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Middle ear pressure and dysfunction of the labyrinth: is there a relationship?
Relationships between middle ear pressure and non-infection-related cochleovestibular dysfunction have been suggested by several authors. According to some data, vertiginous attacks can be prevented by the insertion of a ventilation tube in patients suffering from Meniere's syndrome. The aim of our study was to investigate if the incidence of eustachian tube malfunction and pathologic middle ear pressure is frequent, and if routine implantation of ventilation tubes is reasonable in ears with dysfunctions of the labyrinth, including clinical Meniere's syndrome. So, we determined in our pressure chamber all active and passive parameters of eustachian tube function in 40 patients suffering from Meniere's syndrome, sudden sensory hearing impairment (SSHI), or vestibular neuronitis. Our results disclosed no nonrandom incidence of impaired tubal function among our patients compared to healthy control subjects. Pressure equalization was sufficient in most patients suffering from clinical Meniere's syndrome, and only one patient with vestibular neuronitis presented with a patulous tube. Our results show that impairment of vestibular or cochlear function is not regularly accompanied by eustachian tube dysfunction. Furthermore, no patient reported symptoms while pressure variation was performed. We conclude that variation of middle ear pressure does not usually play a role in the genesis of Meniere's syndrome, vestibular neuronitis, or SSHI. Thus, from our data, we cannot recommend routine implantation of tympanic ventilation tubes in patients suffering from Meniere's syndrome, vestibular neuronitis, or sudden hearing loss.
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Eye movements and brainstem neuronal responses evoked by cerebellar and vestibular stimulation in chicks.
The vestibulo-ocular reflex undergoes adaptive changes that require inputs from the cerebellar flocculus onto brainstem vestibular neurons. As a step toward developing an in vitro preparation in chicks for studying the synaptic basis of those changes, we have elucidated the organization of the pathways through which the flocculus influences vestibulo-ocular movements. Electrical stimulation of the vestibular ampulla evoked brief, contralaterally directed movements in both eyes. Although single current pulses to the flocculus elicited no response, conjunctive stimulation of the flocculus and the vestibular apparatus significantly reduced the vestibularly-evoked movement. Trains of current pulses applied to the flocculus and ampulla evoked eye movements directed toward and away from the side of stimulation, respectively. Recordings from the brainstem revealed neurons that were activated by ipsilateral vestibular stimulation and inhibited by ipsilateral floccular stimulation. Our sample included neurons in the lateral vestibular nucleus, the ventrolateral portion of the medial vestibular nucleus, and the superior vestibular nucleus. Similarities between these findings and those of similar studies in mammals indicate that the chick will provide a good model system for cellular studies of adaptive changes in the vestibulo-ocular reflex.
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Direct and indirect effects of muscimol on medial vestibular nucleus neurones in guinea-pig brainstem slices.
Inhibitory amino acids are considered as major transmitters in the vestibular system. Using intracellular recordings in slices, we applied gamma-aminobutyric acid (GABA) and muscimol (a specific agonist of the GABAA receptor) to the two main types of medial vestibular nucleus neurones (A and B MVNn). In either a high Mg2+/low Ca2+ solution, or a solution containing tetrodotoxin, all MVNn were hyperpolarized by GABA and muscimol. This indicates that both types of MVNn are endowed with postsynaptic, hyperpolarising GABAA receptors. In a normal medium, about half of A and B MVNn were, in contrast, depolarised by GABA and muscimol, whereas the remaining cells were hyperpolarised. These results could be due to a modulation by GABA and muscimol of a tonic GABA release in the slice. Such a release was, indeed, suggested by results showing the depolarising effect of either tetrodotoxin (TTX) or bicuculline, when applied alone. The cells that were depolarised by GABA or muscimol in control conditions were always hyperpolarised in the presence of TTX. Our data therefore suggest that GABA acting at GABAA receptors in the medial vestibular nucleus can play a role either through a postsynaptic hyperpolarising action or indirectly by inhibiting a tonic GABA release, probably resulting from the spontaneous activity of local inhibitory interneurones. A GABAergic regulation of these interneurones could be important in processes of vestibular habituation and/or adaptation.
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A new evaluation of vestibular compensation.
Vestibular compensation process in six patients was examined by means of static (SPG) and kinetic posturography (KPG). SPG was recorded by a stabilometer during standing and KPG was recorded by POLGON so that angular change of shoulder in the frontal plane was measured during stepping. The subjects included three cases with vestibular neuronitis, three cases with bilateral vestibular loss. In vestibular neuronitis, SPG improved earlier than KPG. As a result of vestibular training, initial high levels of SPG and KPG fall precipitously and in the case with sequela, a remarkably high level of KPG gradually decreased. In bilateral vestibular loss, abnormality of KPG tended to persist and those results would be due to the disappearance of a hip strategy. The effect of training upon the case which started from the early days was not shown. However, the case which started from 10 months after the onset showed remarkable improvement of SPG and KPG.
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