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Internuclear neurons in the ocular motor system of frogs.

Medial and lateral rectus motoneurons of frogs were localized after retrograde labeling with horseradish peroxidase (HRP) injected in the medial rectus muscle or applied on the cut end of the abducens nerve. Coordinates of these cell columns were used as target areas for the injection of small amounts of HRP (20-60 nl) and [3H]leucine (25-40 nl) and as search areas for retrogradely and anterogradely labeled internuclear neurons (INT) in in vivo and in vitro experiments. HRP injection in the medial rectus subdivision of the oculomotor nucleus (n = 6) resulted in retrograde labeling of cell bodies in the contralateral principal abducens nucleus. On the average about 16 cells per animal were found. Somatic diameters were about 13.5 +/- 2.8 microns (n = 32). The number and the size of these abducens internuclear neurons (AbINT) are smaller than those of lateral rectus motoneurons (n = 75; diameter: 19 +/- 3.2 microns). A crossed projection of AbINT to medial rectus motoneurons in the contralateral oculomotor nucleus is further supported by autoradiographic results. Following injection of [3H]leucine into the abducens nucleus, a high density of silver grains was visible within the contralateral oculomotor nucleus, mainly in the caudal part of the oculomotor nucleus, where medial rectus motoneurons are located. Injection of [3H]leucine in vivo (n = 4) and in vitro (n = 3) resulted in a similar high density of silver grains within the contralateral oculomotor nucleus, but the background level of silver grains was significantly higher after in vitro (264 +/- 38/2,500 microns2) than after in vivo injections (195 +/- 17/2,500 microns2). HRP injection in the principal abducens nucleus (n = 9) resulted in retrograde labeling of cell bodies in the medial rectus subdivisions of the bilateral oculomotor nuclei. Ipsilateral projections predominated, with about 10 (+/- 8) labeled cells over contralateral projections (about 3 +/- 2). Average diameters of these oculomotor internuclear neurons (OcINT) were again smaller (10.8 +/- 2 microns; n = 18) than those of medial rectus motoneurons (14.4 +/- 3 microns; n = 52). In addition, retrogradely labeled cells were consistently encountered in the bilateral vestibular nuclei, the cerebellar nuclei, the dorsal brainstem caudal to the abducens nuclei, and ipsilaterally in the pretectum. Most of the vestibular neurons were located in the rostral part of the vestibular nuclear complex. These neurons might constitute part of the three-neuronal arc of the vestibulo-ocular reflex in the frog. Labeled cells in the pretectum were restricted to the ipsilateral posterior thalamic nucleus (P).(ABSTRACT TRUNCATED AT 400 WORDS)

Abducens Nerve↗

Why does vertigo become chronic after neuropathia vestibularis?

OBJECTIVE: Vertigo is one of the most frequent complaints in general medical practice and is often linked to psychiatric disorders. A longitudinal study of 67 patients with an acute vestibular disorder was undertaken to clarify if, after experiencing acute vestibular vertigo, certain patients have a higher likelihood of developing chronic, debilitating dizziness despite no evidence of a damaged peripheral vestibular system. METHOD: The severity of dizziness was determined in 67 patients with vestibular neuronitis, 6 months after their release from hospital, using the Vertigo Symptom Scale from Yardley et al. The intensity of anxiety directly after vertigo was experienced, body-related cognitions, illness coping, personality structure, and the recovery of the organ of equilibrium were recorded in order to explain the severity of vertigo that occurred after 6 months. The function of the organ of equilibrium was assessed by using a caloric test. RESULTS: Over a period of 6 months, 13 of the 67 patients (19.4%) reported continuing dizziness after neuropathia vestibularis. Eleven of the 13 patients showed high scores on a scale for measuring vertigo-related symptoms, which can be interpreted as being equivalent to anxiety. The variables of gender, catastrophic thoughts and a dependent personality accounted for 35% of why vertigo became chronic. CONCLUSION: Neuropathia vestibularis represents a risk factor for the development of chronic vertigo. Chronic vertigo after neuropathia vestibularis appears to be equivalent to anxiety and is partly conditional on catastrophic thoughts at the beginning.

Anxiety Disorders↗

Headache in Meniere's disease.

OBJECTIVE: We examined headache in 86 patients with severe or moderately severe Meniere's disease (MD) or with Meniere's syndrome (MS) chosen for intratympanic gentamicin treatment. Forty-five patients with vestibular neuronitis (VN) served as a control group. METHODS: In addition to a clinical examination, the patients filled out a questionnaire concerning their headache. RESULTS: Altogether 60 MD patients (70%) and 26 VN patients (58%) reported headache. Headache was severe in 35 MD patients (58%), moderate in 16 patients (27%) and slight in nine MD patients (15%), and as a whole more severe than that of the VN patients (P < 0.01). The MD patients exhibited significantly more occipital (P < 0.005) and neck headache (P < 0.005) than the VN patients. Analgesics had been used by 82%, antidepressants by 35%, sumatriptan by 13% and carbamazepine and/or amitriptyline by 12% of the MD patients suffering from headache. Pain relief was reported as good by 27%, satisfactory by 60%, poor by 5% of the MD patients and 8% could not rate the pain relief. In this study migraine was diagnosed in 5 MD patients. CONCLUSION: It is concluded that MD is associated with headache that can be handicapping, and tricyclic antidepressants with pain alleviating medication is often needed to treat the headache in MD whereas sumatriptan did not alleviate the headache of the non-migraine patients.

Adult↗

Neurotransmitters regulating vestibular commissural inhibition in the cat.

The present study focuses on the transmitters which control the vestibular neural activity and, in particular, those which regulate commissural inhibition. Extracellular spike recordings were taken from single vestibular neurons of decerebrate cats. Seven-barreled electrodes were used. The barrels, except for the central one, were filled with several transmitter candidates and their specific inhibitors. After isolation of a type I neuron, the chemicals were iontophoretically applied to examine their effects on the activity of the neuron. The results were as follows: i) GABA and glycine markedly decreased spontaneous firing of the neurons, while serotonin did not change the activity. ii) Bicuculline abolished the inhibitory effects of GABA on the neurons. iii) Strychnine also abolished the effects of glycine, iv) Commissural inhibition caused by electrical stimulation of the contralateral labyrinth was not abolished by the application of strychnine but was abolished by bicuculline. We concluded that 1) vestibular type 1 neurons are controlled by GABAergic and glycinergic neurons, and that 2) the commissural inhibition is activated by the GABAA receptor, but not by the GABAB receptor.

Animals↗

Ipsilateral and contralateral projections to the trochlear nucleus arise from different subdivisions in the vestibular nuclei.

Vestibular neurons that project to the trochlear nucleus were studied following unilateral injections of horseradish peroxidase. After 48 h, the animals were perfused, transverse sections were cut, and reacted with diaminobenzidine. After injections centered on the trochlear nucleus, one-third of the labeled neurons were located in the ipsilateral superior (S) vestibular nucleus and almost half were in the contralateral medial (M) vestibular nucleus. Labeled fibers were restricted to the medial longitudinal fasciculus ipsilateral to the injection. This study supports hypotheses, based on physiological data of two vertical vestibulo-ocular pathways; one originating in the ipsilateral S that may be inhibitory and the second originating predominantly from the contralateral M that may be excitatory.

Afferent Pathways↗

Evidence of a sensory processing unit in the mammalian macula.

We cut serial sections through the medial part of the rat vestibular macula for transmission electron microscopic (TEM) examination, computer-assisted 3-D reconstruction, and compartmental modeling. The ultrastructural research showed that many primary vestibular neurons have an unmyelinated segment, often branched, that extends between the heminode (putative site of the spike initiation zone) and the expanded terminal(s) (calyx, calyces). These segments, termed the neuron branches, and the calyces frequently have spine-like processes of various dimensions with bouton endings that morphologically are afferent, efferent, or reciprocal to other macular neural elements. The major questions posed by this study were whether small details of morphology, such as the size and location of neuronal processes or synapses, could influence the output of a vestibular afferent, and whether a knowledge of morphological details could guide the selection of values for simulation parameters. The conclusions from our simulations are (1) values of 5.0 k omega cm2 for membrane resistivity and 1.0 nS for synaptic conductance yield simulations that best match published physiological results; (2) process morphology has little effect on orthodromic spread of depolarization from the head (bouton) to the spike initiation zone (SIZ); (3) process morphology has no effect on antidromic spread of depolarization to the process head; (4) synapses do not sum linearly; (5) synapses are electrically close to the SIZ; and (6) all whole-cell simulations should be run with an active SIZ.

Acoustic Maculae↗

Neuronal responses to vestibular stimulation in the guinea pig hypothalamic paraventricular nucleus.

We investigated the effects of caloric stimulation on neuronal activity in the hypothalamic paraventricular nucleus (PVN) in anesthetized guinea pigs. Hot water stimulation of the contralateral labyrinth produced excitation in 29.4% of the PVN neurons tested, while cold water produced excitation in 22.2% of the neurons. Hot water resulted in inhibition of 22.4% of the neurons and cold water inhibition of 24.7% of the neurons. Intracranial vestibular nerve section greatly reduced responsiveness of the PVN neurons to caloric stimulation, indicating that the majority of the responses observed were vestibular in origin. The response pattern of the individual PVN neurons was similar following hot and cold water stimulation and after stimulation of the contralateral and ipsilateral labyrinths. These results suggest that the PVN neurons receive vestibular afferents bilaterally according to the intensity of vestibular stimulation, with the information received probably integrated in the hypothalamus to participate in vestibulo-autonomic reflexes.

Animals↗

Medial vestibular nucleus in the guinea-pig: NMDA-induced oscillations.

We have recently shown in vivo that N-Methyl-D-Aspartate (NMDA) receptors are present in the guinea-pig vestibular complex and demonstrated that they are involved in the regulation of the resting discharge of vestibular neurones. A parallel in vitro study has identified in the guinea-pig medial vestibular nuclei (MVN) two main neuronal cell types, A and B MVNn, differing by their intrinsic membrane properties. One subtype of B MVNn was further characterized by the presence of a low threshold calcium spike (LTS). The present study investigated in vitro the responses of these different cell types to NMDA. Both A and B MVNn were depolarized by NMDA, which also induced a decrease in membrane resistance and an increase in the spontaneous firing rate. These effects could be blocked by D-AP5, a specific antagonist of NMDA receptors. Following a 10-30 mV hyperpolarization, a long-lasting oscillatory behavior could be induced in presence of NMDA. These oscillations were however restricted to the subtype of B MVNn without LTS. The NMDA-induced oscillations were tetrodotoxine-resistant, but could be eliminated by D-AP5 or by replacing sodium with choline. Functional implications of this oscillatory behavior are discussed.

2-Amino-5-phosphonovalerate↗

Electrophysiological correlates of the reversed postoptokinetic nystagmus in the rabbit: activity of vestibular and floccular neurons.

Unit activity changes accompanying the optokinetic nystagmus (OKN) and reversed postoptokinetic nystagmus (RPN) in the rabbit were examined in 180 vestibular and floccular neurons. After initial charging of the RPN generator by 60-min optokinetic stimulation, a sequence of 1-min optokinetic stimulation (OKN) followed by 1-min darkness (RPN) and 1-min illumination of the stationary optokinetic drum (L), was cycled while corresponding unit activity changes were recorded during 3--5 cycles and evaluated with a computer. About 50% of vestibular neurons (type A) increased their activity during OKN and/or decreased it during RPN with respect to the L period, whereas 24% (type B) reached in a reciprocal manner. The remaining neurons were either unaffected or responded in an atypical way. Most floccular neurons (75%) were activated during ipsilateral optokinetic stimulation, but were not significantly affected by RPN. It is suggested that the neural trace of RPN develops in the vestibular complex and vestibulocerebellum as a part of the process compensating for the effect of continued optokinetic stimulation.

Animals↗

Short latency vestibular evoked responses to linear acceleration stimuli in small mammals: masking effects and experimental applications.

Different potential were recorded from a site close to the 8th nerve in chinchillas in response to linear acceleration pulses. Acoustic masking allowed us to distinguish between an early response (within 1 ms after initiation of the acceleration) of probable vestibular origin and later responses of probable cochlear origin. The latter were abolished by intense acoustic masking and by surgical ablation of the cochlea. The early potential was slightly reduced by simultaneous acoustic masking with white noise above 65 dB SPL and was most sensitive to 1 kHz narrow band masking. Vestibular neurons seem to be stimulated by high frequency movements of their hair cell cilia, and vestibular compound action potentials can be recorded as soon as a sufficient number of neurons are brought to a synchronized response. These vestibular evoked potentials may provide a tool for experimental studies on vestibular function in laboratory animals.

Acceleration↗

Properties of saccular nerve-activated vestibulospinal neurons in cats.

Axonal pathways, projection levels, conduction velocities, and locations of the cell bodies of saccular nerve-activated vestibulospinal neurons were studied in decerebrated cats and anesthetized cats, using a collision test of orthodromic and antidromic spikes. The saccular nerve was selectively stimulated by bipolar tungsten electrodes. Three monopolar electrodes were inserted into the left and right lateral vestibulospinal tract (LVST) and medial vestibulospinal tract (MVST) of the C1 segment, to determine the pathway of axons. Three pairs of similar electrodes were positioned bilaterally in the C3-4, T1, and L3 segments to examine projection levels. Another monopolar electrode was placed in the oculomotor nucleus to determine whether saccular nerve-activated vestibulospinal neurons have branches ascending to the oculomotor nucleus. Of 145 vestibular neurons orthodromically activated by stimulation of the saccular nerve, 46 were activated from the C1 segment antidromically. Forty-three were second-order vestibulospinal neurons and 3 were third-order vestibulospinal neurons. Four saccular nerve-activated vestibulospinal neurons were also antidromically activated from the oculomotor nucleus. Sixty-three percent of the saccular nerve-activated vestibulospinal neurons descended through the MVST; one-third of these terminated in the upper cervical segments, one-third reached the lower cervical segments and the remaining one-third reached the upper thoracic segments. Thirty percent of the saccular nerve-activated vestibulospinal neurons descended through the ipsilateral LVST; most of these reached the upper thoracic segments. Seven percent of the saccular nerve-activated vestibulospinal neurons descended through the contralateral vestibulospinal tracts terminating in the upper cervical segments. Most of the saccular nerve-activated vestibulospinal neurons originated in the caudal part of the lateral nucleus and rostral part of the descending nucleus.

Animals↗

Tonic gravity changes alter gene expression in the efferent vestibular nucleus.

To assess effects of tonic gravity changes on efferent vestibular neurons, immediate early gene (IEG) protein expression was compared in the efferent vestibular nucleus (EVe) of adult rats exposed to microgravity during the NASA Neurolab Mission (STS-90), and matching control animals on the ground. Rats sacrificed 1 day and 12 days after launch (experiencing approximately 0g) showed significantly fewer IEG protein-expressing cells than corresponding ground control animals (at 1 g). Normal IEG protein-expressing cell numbers reappeared within I day after flight animals returned to earth, and were maintained at 14 days after landing. EVe neurons appear to play a role in gravity-induced modifications of vestibular hair cell synapses; a contribution to gravity-induced plasticity of the vestibulo-ocular reflex (VOR) is also suggested.

Animals↗

Modelling non-linearities in the vestibulo-ocular reflex (VOR) after unilateral or bilateral loss of peripheral vestibular function.

We recorded the vestibulo-ocular reflex (VOR) in 18 normal subjects, 50 patients with unilateral loss of vestibular function and 18 patients with bilateral loss of vestibular function. The unilateral cases had either partial loss (i.e. vestibular neuronitis or Meniere's disease) or total loss (i.e. vestibular nerve section), whereas bilateral cases had only partial loss (i.e. due to ototoxicity or to suspected microangiopathy, secondary to severe kidney disease). Tests were performed at 1/6-Hz passive head rotation in the dark, with peak head velocities ranging from 125 to 190 degrees/s. We report on the distinct VOR non-linearities observed in unilateral versus bilateral patients: whereas unilateral patients all exhibit an asymmetric hypofunction with decreasing VOR gain at higher head velocities, bilateral patients have a more severe but symmetric hypofunction associated with increasing VOR gain at higher head velocities. We present a model study that can duplicate the nature of these characteristics, based mainly on peripheral non-linear semicircular canal characteristics and secondary central compensation. Theoretical analyses point to the importance of clinical test parameters (rotation speed and frequency) in the determination of a functional VOR and the detection of reflex non-linearities, so that test protocols can seriously bias the evaluation of adequate functional recovery.

Afferent Pathways↗

The effects of the "vestibular sedative" drug, Flunarizine upon the vestibular and oculomotor systems.

The effects of the "vestibular sedative" drug Flunarizine upon the oculomotor functions of pursuit and voluntary saccades and upon the vestibular response (to rotational stimuli) were assessed in twenty volunteer subjects. The study was then extended to three patients with chronic imbalance of central origin who had reported a beneficial symptomatic response to the drug. Three of the volunteer subjects were found to have a directional preponderance (presumed to arise from peripheral dysfunction). In the remaining seventeen normal subjects Flunarizine was found to reduce the amplitudes of fast phases of vestibular nystagmus. The directional preponderance in the other three subjects was redressed through production of fast phases which were of lower and more uniform amplitude. In the patients, in addition to a reduction in fast phase amplitude, there was a reduction or abolition of after nystagmus. In no case was any reduction in slow phase velocity observed. Pursuit and voluntary saccades were unaffected by the drug. It was concluded, on the basis that the fast phases of nystagmus are centrally generated, that Flunarizine has a central action rather than a depressant effect upon the vestibular end organ. In view of known oculomotor physiology and pharmacology it is proposed that vestibular sedatives act by depression of Type II vestibular neurons, and modification of the functional relationships between the vestibular nuclei, the perihypoglossal nuclei and the flocculus of the cerebellum. A trial of vestibular active drug is indicated particularly in patients in whom asymmetry of the vestibular response and/or abnormal after nystagmus is demonstrated.

Adult↗

Development of vestibular afferent projections into the hindbrain and their central targets.

In contrast to most other sensory systems, hardly anything is known about the neuroanatomical development of central projections of primary vestibular neurons and how their second order target neurons develop. Recent data suggest that afferent projections may develop not unlike other sensory systems, forming first the overall projection by molecular means followed by an as yet unspecified phase of activity mediated refinement. The latter aspect has not been tested critically and most molecules that guide the initial projection are unknown. The molecular and topological origin of the vestibular and cochlear nucleus neurons is also only partially understood. Auditory and vestibular nuclei form from several rhombomeres and a given rhombomere can contribute to two or more auditory or vestibular nuclei. Rhombomere compartments develop as functional subdivisions from a single column that extends from the hindbrain to the spinal cord. Suggestions are provided for the molecular origin of these columns but data on specific mutants testing these proposals are not yet available. Overall, the functional significance of both overlapping and segregated projections are not yet fully experimentally explored in mammals. Such lack of details of the adult organization compromises future developmental analysis.

Animals↗

The influence of vestibular and cochlear aqueducts on vestibular response to middle ear pressure changes in guinea pigs.

The responses of primary vestibular neurons and perilymphatic pressure changes to middle ear pressure were investigated in guinea pigs with obstructed vestibular or cochlear aqueduct (closed VA or closed CA group) in order to clarify the influence of VA and CA on pressure-induced vestibular response. Although the neural response rates and the amount of perilymphatic pressure change in the closed VA group resembled those in the control group, these values in the closed CA group were higher than in the control group. Patency of the CA had a more significant effect on the vestibular response to middle ear pressure change than patency of the VA.

Animals↗

GABA-like immunoreactivity in the cochlea of the developing mouse.

GABA-like immunoreactivity was studied in surface preparations of cochleas from postnatal developing mice, and GAD-like immunoreactivity was studied in the adult. GABA-positive fibres are already present at birth; they innervate both the inner and outer hair cells and some spiral ganglion cells. The GABA-positive fibres that enter via the intraganglionic bundle send collaterals to the spiral ganglion and to the hair cell region. Fibres that enter along the central processes of spiral neurons end predominantly among the spiral ganglion cells. A few spiral neurons display pericellular rings of GABA-positive boutons at birth. In older animals, the endings occur on a small number of spiral ganglion cells either as rings or as brush formations. The early GABA-positive fibres reach the inner hair cells around the second day and the outer hair cells (of the upper turns only) around the seventh day. In 12-day animals, tunnel fibres arborize in the outer hair cell region; their collaterals make contacts with the outer hair cells within four to eight cell-wide segments, distributing the endings high, up to the reticular plate. In older animals, fibres (both GABA-and GAD-positive) may innervate single vertical rows of outer hair cells. In the maturing and the adult cochlea, the GABA-positive component of the inner spiral bundle is conspicuous and extends along the entire cochlear length, but the innervation of the outer hair cells comprises only the mid and apical turns. GABA-positive nerve cells occur among the small vestibular neurons, occasionally among the cells of eighth nerve nucleus and only exceptionally in the spiral ganglion. In the adult animal, GAD-positive cells, although uncommon, were observed among the spiral neurons. In the developing animal, GABA-positive fibres give rise to transitory formations: (1) a convoluted plexus running beneath and among the radial bundles and (2) a sparse plexus, continuous with the inner spiral bundle and running in the upper plane of the inner spiral sulcus. GABA-like immunoreactivity was also observed in neuronal growth cones and in some fibres running along blood vessels. In conclusion, GABA immunoreactive fibres appear to reach the cochlea by two routes: via the intraganglionic bundle and to a much lesser extent via the central bundles of the spiral ganglion. The fibres innervate sensory cells and also some spiral neurons. The occasional presence of GABA-positive neurons in the vestibular ganglion, in the VIIIth nerve nucleus, and exceptionally among the spiral neurons raises the possibility of a local GABAergic circuitry within the inner ear.

Animals↗

Efferent system degeneration in the human temporal bone.

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

Animals↗