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Otolith and canal integration on single vestibular neurons in cats.

In this review, based primarily on work from our laboratory, but related to previous studies, we summarize what is known about the convergence of vestibular afferent inputs onto single vestibular neurons activated by selective stimulation of individual vestibular nerve branches. Horizontal semicircular canal (HC), anterior semicircular canal (AC), posterior semicircular canal (PC), utricular (UT), and saccular (SAC) nerves were selectively stimulated in decerebrate cats. All recorded neurons were classified as either projection neurons, which consisted of vestibulospinal (VS), vestibulo-oculospinal (VOS), vestibulo-ocular (VO) neurons, or non-projection neurons, which we simply term "vestibular'' (V) neurons. The first three types could be successfully activated antidromically from oculomotor/trochlear nuclei and/or spinal cord, and the last type could not be activated antidromically from either site. A total of 1228 neurons were activated by stimulation of various nerve pair combinations. Convergent neurons were located in the caudoventral part of the lateral, the rostral part of the descending, and the medial vestibular nuclei. Otolith-activated vestibular neurons in the superior vestibular nucleus were extremely rare. A high percentage of neurons received excitatory inputs from two nerve pairs, a small percentage received reciprocal convergent inputs and even fewer received inhibitory inputs from both nerves. More than 30% of vestibular neurons received convergent inputs from vertical semicircular canal/otolith nerve pairs. In contrast, only half as many received convergent inputs from HC/otolith-nerve pairs, implying that convergent input from vertical semicircular canal and otolith-nerve pairs may play a more important role than that played by inputs from horizontal semicircular canal and otolith-nerve pairs. Convergent VS neurons projected through the ipsilateral lateral vestibulospinal tract (i-LVST) and the medial vestibulospinal tract (MVST). Almost all the VOS neurons projected through the MVST. Convergent neurons projecting to the oculomotor/trochlear nuclei were much fewer in number than those projecting to the spinal cord. Some of the convergent neurons that receive both canal and otolith input may contribute to the short-latency pathway of the vestibulocollic reflex. The functional significance of these convergences is discussed.

Animals↗

Vestibular neuronitis. A clinical and electro-oculographic analysis.

Thirty patients, primarily diagnosed as having vestibular neuronitis, were investigated with a test battery consisting of neuro-otological, neuro-ophthalmological, neurological examinations and electro-oculography. Initial routine examination failed to reveal involvement of structures outside the vestibular nerve, whereas neurological evaluation and analysis of the cerebrospinal fluid indicated an intrinsic central nervous system (CNS) disorder in 6 cases. The electro-oculographic analysis revealed abnormalities supporting a 'central' cause of the vertigo in 12 cases. Altogether 13 patients showed signs of a possible intrinsic CNS disorder. Consequently, although routine examination may indicate a diagnosis of vestibular neuronitis, the patient concerned frequently has signs of an intrinsic CNS disorder and not a disorder of the peripheral nerve.

Adult↗

GATA3 and NeuroD distinguish auditory and vestibular neurons during development of the mammalian inner ear.

The function of the zinc finger transcription factor GATA3 was studied in a newly established, conditionally immortal cell line derived to represent auditory sensory neuroblasts migrating from the mouse otic vesicle at embryonic day E10.5. The cell line, US/VOT-33, expressed GATA3, the bHLH transcription factor NeuroD and the POU-domain transcription factor Brn3a, as do auditory neuroblasts in vivo. When GATA3 was knocked down reversibly with antisense oligonucleotides, NeuroD was reversibly down-regulated. Auditory and vestibular neurons form from neuroblasts that express NeuroD and that migrate from the antero-ventral, otic epithelium at E9.5-10.5. On the medial side, neuroblasts and epithelial cells express GATA3 but on the lateral side they do not. At E13.5 most auditory neurons express GATA3 but no longer express NeuroD, whereas vestibular neurons express NeuroD but not GATA3. Neuroblasts expressing NeuroD and GATA3 were located in the ventral, otic epithelium, the adjacent mesenchyme and the developing auditory ganglion. The results suggest that auditory and vestibular neurons arise from different, otic epithelial domains and that they gain their identity prior to migration. In auditory neuroblasts, NeuroD appears to be dependent on the expression of GATA3.

Animals↗

Diazepam enhances cerebellar inhibition on vestibular neurons.

The spontaneous neuronal activity of the lateral (LVN) and the superior (SVN) vestibular nuclei was analysed before and after the intravenous (i.v.) injection of diazepam in encéphale isolé', decerebrate and cerebellectomized rabbits. The inhibition of vestibular neurons was dependent on the integrity of cerebellar connections with LVN, while these links were partially responsible for the diazepam inhibition on SVN. A role of spinal and telediemesencephalic structures was not recognized. Considering that diazepam does not increase the activity of Purkinje cells, the drug effect ought to be exerted at the level of the Purkinje cell junctions with the cerebellar nuclei and with the vestibular neurons. GABA being the neurotransmitter released by Purkinje cells evidence is provided for a diazepam potentiation of the GABAergic mechanism at the level of vestibular system.

Animals↗

Compensatory process of vestibular neuronitis. From findings of combined galvanic test and caloric test.

The compensatory process of vestibular neuronitis in 7 patients was followed up and evaluated using the Combined Galvanic Test (CGT) and other neuro-otological data. CGT is the simultaneous recording of both galvanic eye movement (GEM) and galvanic body sway (GBS), and has proved to be reliable in the diagnosis of retrolabyrinthine disorders. The results were as follows: The subjective symptoms remained in 3 cases from 1 month to 1 year. The recovery of the GBS response was seen earlier than that of both GEM and caloric responses. The recovery of GEM and caloric responses was observed at almost the same time. We observed the favorable recovery process of caloric response and GEM response in some cases which had recovery of GBS response within 4 weeks and suggest that the system of GBS response is different from that of GEM and caloric response. However, the systems of the latter two may be the same. We assume that the recovery of GBS response is earlier than that of GEM and caloric responses because the otolithic system recovers more easily than the semicircular canal system. The CGT and caloric test were reliable in examining the compensatory process of vestibular neuronitis.

Adult↗

Axon collaterals of anterior semicircular canal-activated vestibular neurons and their coactivation of extraocular and neck motoneurons in the cat.

We studied the ascending and descending axonal trajectories of excitatory vestibular neurons related to the anterior semicircular canal, by means of local stimulation and spike-triggered signal averaging techniques in anesthetized cats. More than 200 vestibular neurons related to the ampullary nerve of the anterior semicircular canal (ACN) were identified as vestibulo-ocular neurons by antidromic stimulation of the contralateral inferior oblique (IO) muscle motoneuron pool. In the descending, medial and ventral lateral nuclei, about 60% of these vestibulo-ocular neurons were also activated antidromically by upper cervical spinal cord stimulation (vestibulo-ocular-collic (cervical) = VOC). These VOC neurons produced unitary EPSPs in the majority of neck extensor motoneurons located at the C1 segment. None of the VOC neurons had axons descending as far as the thoracic level. Most of these VOC neurons were activated monosynaptically following stimulation of the ACN. The conduction velocity of the descending axons of VOC neurons was approximately 63 m/s, which was significantly faster than that of the ascending axons. The remaining 40% of the vestibulo-ocular neurons were not activated antidromically following spinal cord stimulation at intensities of 1 mA or more (vestibulo-ocular = VO). Most of the VO neurons were activated polysynaptically by ACN stimulation. The superior vestibular nucleus contained VO neurons that were activated mono- and polysynaptically following ACN stimulation.

Animals↗

Effect of labyrinthectomy on the spike generator of vestibular neurons in the guinea pig.

In the guinea pig, in the absence of any stimulation, all the neurons of the vestibular nuclei are tonically firing. After an ipsilateral labyrinthectomy, these neurons first cease to fire but recover their previous discharge in 7 days. Here, we tested whether a modification of the spike generator, the process transforming synaptic currents into spike patterns, could be a factor underlying this restoration. For this purpose, we studied the firing rate responses of neurons of the medial vestibular nucleus in brain stem slices to intracellularly injected currents. We conclude that although labyrinthectomy induces some plastic changes in the excitability of the neurons of the medial vestibular nucleus, these changes do not underlie the restoration of activity which occurs in these neurons when they are deprived of their labyrinthine input.

Action Potentials↗

Effects of noradrenaline on the firing rate of vestibular neurons.

The effects of microiontophoretic noradrenaline on the firing rate of neurons located in the vestibular complex have been studied in anaesthetized rats. Eighty-five per cent of the neurons tested in all the vestibular nuclei modified their background firing rate upon noradrenaline application, generally by reducing it (86% of them). In few cases inhibitions were followed by a rebound. Responses were dose-dependent. No significant difference was found between vestibular neurons projecting to the spinal cord and those delivering their fibres to the oculomotor complex. Phentolamine, an alpha-adrenergic antagonist, blocked the noradrenaline-evoked inhibitions, whereas beta-adrenergic antagonist timolol was ineffective or enhanced them. Furthermore, responses were blocked by yohimbine, an alpha 2-adrenergic antagonist, and mimicked by clonidine, an alpha 2-adrenergic agonist, in the majority of neurons. In few cases prazosin, an alpha 1-adrenergic antagonist, was able to antagonize weak inhibitions and phenylephrine, an alpha 1-adrenergic agonist, to evoke an inhibitory effect blocked by prazosin. Isoproterenol, a beta-adrenergic agonist was totally ineffective on the neuronal firing rate. It is concluded that noradrenaline can modify the level of neuronal activity in the vestibular complex by acting mostly, but not exclusively, through alpha 2-adrenergic receptors. An influence of noradrenergic systems on the vestibular function by a direct action of noradrenaline inside the vestibular nuclei is proposed.

Action Potentials↗

Multimodal signal integration in vestibular neurons of the primate fastigial nucleus.

The rostral fastigial nucleus contains vestibular neurons, which presumably are involved in spinal mechanisms (neck, gait, posture) and which are not modulated with individual eye movements. Single-unit recordings in the alert behaving monkey during natural stimulus conditions reveal that virtually all neurons demonstrate integration of several sensory inputs. This applies not only for canal-canal and canal-otolith interaction, but also for otolith-otolith interaction. There is also some evidence that most neurons receive not only an utriculus but also a sacculus input. Furthermore, most neurons also respond to large-field optokinetic stimulation, reflecting visual-vestibular interaction. Neurons are also affected by the head on trunk position, which would allow these neurons to operate in a body-centered rather than a head-centered reference frame. These complex, multisensory features could permit fastigial nucleus neurons to rather specifically affect spinal motor functions.

Animals↗

Neurotologic evidence of central and peripheral involvement in patients with vestibular neuronitis.

Quantitative vestibulo-oculomotor tests and auditory brain stem responses were studied in 22 patients with vestibular neuronitis in a search for evidence of CNS affection. Such evidence was found in 16 of the 22; only in the other six could the examination findings be regarded as the result of damage limited to vestibular neuroepithelium or nerve. It is concluded that vestibular neuronitis can cause CNS signs by itself, probably because of inflammation in the vicinity of the vestibular nerve.

Adolescent↗

The differential expression of low-threshold sustained potassium current contributes to the distinct firing patterns in embryonic central vestibular neurons.

The principal cells of the chick tangential nucleus are second-order sensory neurons that participate in the three-neuron vestibulo-ocular and vestibulocollic reflexes. In postnatal animals, second-order vestibular neurons fire repetitively on depolarization. Previous studies have shown that, although this is an important feature for normal reflex function, it is only acquired gradually during embryonic development. Whereas at 13 embryonic days (E13) the principal cells accommodate after firing a single spike, at E16 a few principal cells repetitively can fire multiple action potentials on depolarization. Finally, in the hatchling, the vast majority of principal cells is capable of nonaccommodating firing on depolarization. As a first step in understanding the mechanisms underlying developmental change in excitability of these second-order vestibular neurons, we analyzed the outward potassium currents and their role in accommodation, using brainstem slices at E16. The principal cells exhibited transient and sustained potassium currents, with both of these containing calcium-dependent components. Further, both high- and low-threshold sustained potassium currents have been distinguished. The low-threshold dendrotoxin-sensitive sustained potassium current (IDS) is associated with principal cells that accommodate and is not expressed in those that fire repetitively. Finally, blocking of IDS transforms accommodating cells into neurons capable of firing trains of action potentials on depolarization. These findings indicate that suppression of IDS during development is sufficient to transform accommodating principal cells into nonaccommodating firing neurons and suggests that developmental regulation of this current is necessary for the establishment of normal vestibular function.

Action Potentials↗

[Electrophysiologic and anatomic demonstration of inhibitory commisural vestibular neurons in the tench (Tinca tinca)].

Horseradish peroxydase was injected intracellularly in some of the medullary neurons which, in Fish, exhibit a passive hyperpolarizing potential after spinal cord stimulation (this indicates that such neurons both electrical and chemical inhibitions of the Mauthner cells). With positive staining, commissural vestibular neurons were identified; their axons cross the midline and they establish connexions with the Mauthner cell and with vestibular neurons of both sides. Thus the existence of a crossed vestibular inhibitory pathway, previously suggested by electrophysiological studies in lower Vertebrates as well as in Mammals, is now correlated with histological evidence.

Animals↗

Axonal branching in the trochlear and oculomotor nuclei of single vestibular neurons activated from the posterior semicircular canal nerve in the cat.

Axonal branches of single vestibular neurons activated by stimulation of the ampullary nerve of the posterior semicircular canal in the cat were studied by means of local antidromic stimulation in the trochlear and the oculomotor nucleus. These vestibulo-ocular neurons were located in the rostral half of the descending vestibular nucleus and the lateral part of the medial vestibular nucleus. The majority of vestibulo-ocular neurons projecting to the inferior rectus motoneuron pool in the contralateral oculomotor nucleus was activated antidromically from the contralateral trochlear nucleus as well. This suggests that axonal branches of a single vestibular neuron project to both nuclei.

Action Potentials↗

Direct projection of type II vestibular neurons to eye movement-related pause neurons in the cat pontine reticular formation.

Brain stem pause neurons play an important role in the regulation of rapid eye movements. However, the input sources that drive pause neurons are uncertain. In the present study, horizontal canal type II neurons in the medial vestibular nucleus were antidromically activated by electrical stimulation of the pause neuron region. Systematic microstimulation tracks within that region showed an antidromic activation pattern of low-threshold sites separated by high-threshold sites consistent with axonal branching of type II neurons in the pause neuron region. Spike-triggered averaging of single spontaneously firing type II vestibular neuronal discharges in the pause neuron region resulted in short-latency, positive field responses. These results supported the conclusion that horizontal canal type II neurons of the medial vestibular nucleus project to and inhibit pause neurons monosynaptically.

Animals↗

The influence of middle ear pressure changes on the primary vestibular neurons in guinea pigs.

The responses of primary vestibular neurons and perilymphatic pressure changes to middle ear pressure stimuli in guinea pigs were investigated in order to clarify the direct effects of pressure stimulus on the vestibular apparatus. The vestibular response was related to the amount of middle ear pressure change applied at a rate of +/- 100 mmH2O/s. The neural response rates of vestibular units to positive pressure in the middle ear were significantly larger than those to negative pressure. The time course pattern of the perilymphatic pressure change resembled that of the response of the vestibular units, indicating that the vestibular response is elicited by middle ear pressure via the pressure transmitted in the inner ear.

Animals↗

Second-order vestibular neurons form separate populations with different membrane and discharge properties.

Membrane and discharge properties were determined in second-order vestibular neurons (2 degrees VN) in the isolated brain of grass frogs. 2 degrees VN were identified by monosynaptic excitatory postsynaptic potentials after separate electrical stimulation of the utricular nerve, the lagenar nerve, or individual semicircular canal nerves. 2 degrees VN were classified as vestibulo-ocular or -spinal neurons by the presence of antidromic spikes evoked by electrical stimulation of the spinal cord or the oculomotor nuclei. Differences in passive membrane properties, spike shape, and discharge pattern in response to current steps and ramp-like currents allowed a differentiation of frog 2 degrees VN into two separate, nonoverlapping types of vestibular neurons. A larger subgroup of 2 degrees VN (78%) was characterized by brief, high-frequency bursts of up to five spikes and the absence of a subsequent continuous discharge in response to positive current steps. In contrast, the smaller subgroup of 2 degrees VN (22%) exhibited a continuous discharge with moderate adaptation in response to positive current steps. The differences in the evoked spike discharge pattern were paralleled by differences in passive membrane properties and spike shapes. Despite these differences in membrane properties, both types, i.e., phasic and tonic 2 degrees VN, occupied similar anatomical locations and displayed similar afferent and efferent connectivities. Differences in response dynamics of the two types of 2 degrees VN match those of their pre- and postsynaptic neurons. The existence of distinct populations of 2 degrees VN that differ in response dynamics but not in the spatial organization of their afferent inputs and efferent connectivity to motor targets suggests that frog 2 degrees VN form one part of parallel vestibulomotor pathways.

Action Potentials↗

Modelling transfer characteristics of vestibular neurons in the fastigial nucleus of the behaving monkey on the basis of canal-otolith interaction.

The interaction of vestibular inputs with different dynamic and spatial behavior, i.e., canal-otolith interaction, leads to spatio-temporal convergence. Vestibular neurons in the fastigial nucleus often exhibit spatio-temporal convergence. The present report demonstrates that the discharge rates of most vestibular neurons in the primate fastigial nucleus can be simulated at different stimulus frequencies and orientations by a simple linear summation of the signals of the semicircular canals and the otoliths. In this way, a number of complex characteristics that depend on frequency, i.e. changing response-vector orientations, large phase changes, absence and presence of spatio-temporal convergence, can be easily explained.

Action Potentials↗