A volumetric comparison of the vestibular nuclei in primates

The volumes of each of the four vestibular nuclei, superior, lateral, medial and descending, were measured in 80 brains from 2 species of Scandentia, 18 species of prosimians, and 26 species of anthropoids. Size indices were calculated by comparing species-specific points to the nucleus volume-body weight allometry in prosimians, where the average prosimian was set at 1.00. The indices range from 1.78 in Saimiri to 0.48 in Gorilla, and the distributions by families overlap partially or completely. The observed trend in size indices is independent of changes in the neocortex and the ventral pons; average indices are 1.35 in New World monkeys, 1.20 in Old World monkeys, 0.74 in apes, 0.82 in man. Among prosimians, Galago, Galagoides and Tarsius (leaping locomotion) show significantly higher indices than Nycticebus, Loris and Perodicticus (slow movement without leaping). The lateral vestibular nuclear indices in Pongidae and man are extremely low, about half of those of the average prosimians. Correlation coefficients of size indices between the vestibular nuclei and other motor nuclei, such as the cerebellar nuclei, ventral pons and striatum, are analysed. The ratio of the vestibular nuclear volumes to the total brain volumes and the distribution of percentages of each vestibular nuclear volume to the total complex are also obtained.     

Neurogenic potential of the vestibular nuclei and behavioural recovery time course in the adult cat are governed by the nature of the vestibular damage

Functional and reactive neurogenesis and astrogenesis are observed in deafferented vestibular nuclei after unilateral vestibular nerve section in adult cats. The newborn cells survive up to one month and contribute actively to the successful recovery of posturo-locomotor functions. This study investigates whether the nature of vestibular deafferentation has an incidence on the neurogenic potential of the vestibular nuclei, and on the time course of behavioural recovery. Three animal models that mimic different vestibular pathologies were used: unilateral and permanent suppression of vestibular input by unilateral vestibular neurectomy (UVN), or by unilateral labyrinthectomy (UL, the mechanical destruction of peripheral vestibular receptors), or unilateral and reversible blockade of vestibular nerve input using tetrodotoxin (TTX). Neurogenesis and astrogenesis were revealed in the vestibular nuclei using bromodeoxyuridine (BrdU) as a newborn cell marker, while glial fibrillary acidic protein (GFAP) and glutamate decarboxylase 67 (GAD67) were used to identify astrocytes and GABAergic neurons, respectively. Spontaneous nystagmus and posturo-locomotor tests (static and dynamic balance performance) were carried out to quantify the behavioural recovery process. Results showed that the nature of vestibular loss determined the cellular plastic events occurring in the vestibular nuclei and affected the time course of behavioural recovery. Interestingly, the deafferented vestibular nuclei express neurogenic potential after acute and total vestibular loss only (UVN), while non-structural plastic processes are involved when the vestibular deafferentation is less drastic (UL, TTX). This is the first experimental evidence that the vestibular complex in the brainstem can become neurogenic under specific injury. These new data are of interest for understanding the factors favouring the expression of functional neurogenesis in adult mammals in a brain repair perspective, and are of clinical relevance in vestibular pathology.     

Synaptic Plasticity in Medial Vestibular Nucleus Neurons: Comparison with Computational Requirements of VOR Adaptation

Background

Vestibulo-ocular reflex (VOR) gain adaptation, a longstanding experimental model of cerebellar learning, utilizes sites of plasticity in both cerebellar cortex and brainstem. However, the mechanisms by which the activity of cortical Purkinje cells may guide synaptic plasticity in brainstem vestibular neurons are unclear. Theoretical analyses indicate that vestibular plasticity should depend upon the correlation between Purkinje cell and vestibular afferent inputs, so that, in gain-down learning for example, increased cortical activity should induce long-term depression (LTD) at vestibular synapses.

Methodology/Principal Findings

Here we expressed this correlational learning rule in its simplest form, as an anti-Hebbian, heterosynaptic spike-timing dependent plasticity interaction between excitatory (vestibular) and inhibitory (floccular) inputs converging on medial vestibular nucleus (MVN) neurons (input-spike-timing dependent plasticity, iSTDP). To test this rule, we stimulated vestibular afferents to evoke EPSCs in rat MVN neurons in vitro. Control EPSC recordings were followed by an induction protocol where membrane hyperpolarizing pulses, mimicking IPSPs evoked by flocculus inputs, were paired with single vestibular nerve stimuli. A robust LTD developed at vestibular synapses when the afferent EPSPs coincided with membrane hyperpolarisation, while EPSPs occurring before or after the simulated IPSPs induced no lasting change. Furthermore, the iSTDP rule also successfully predicted the effects of a complex protocol using EPSP trains designed to mimic classical conditioning.

Conclusions

These results, in strong support of theoretical predictions, suggest that the cerebellum alters the strength of vestibular synapses on MVN neurons through hetero-synaptic, anti-Hebbian iSTDP. Since the iSTDP rule does not depend on post-synaptic firing, it suggests a possible mechanism for VOR adaptation without compromising gaze-holding and VOR performance in vivo.     

Activity of premotor vestibular neurons in the alert cat

The activity of medial vestibular nucleus neurons projecting to the contralateral abducens nucleus (premotor vestibular neurons) has been recorded during spontaneous and vestibular induced eye movements in the alert cat. Recorded neurons were identified by their antidromic activation from the abducens nucleus and by the post-synaptic field potential induced in this nucleus. The activity of identified medial vestibular neurons increased significantly with horizontal eye position and velocity toward the contralateral side, and decreased abruptly during ipsilateral saccades. The activity of these neurons was also related to head velocity toward the ipsilateral side. The functional role and origin of eye position and velocity signals present in these vestibular neurons are discussed.     

Central adaptation models of the vestibulo-ocular and optokinetic systems

A theoretical analysis of two models of the vestibulo-ocular and optokinetic systems was performed. Each model contains a filter element in the vestibular periphery to account for peripheral adaptation, and a filter element in the central vestibulooptokinetic circuit to account for central adaptation. Both models account for1 adaptation, i.e. a response decay to a constant angular acceleration input, in both peripheral vestibular afferent and vestibulo-ocular reflex (VOR) responses and2 the reversal phases of optokinetic after-nystagmus (OKAN) and the VOR and3 oscillatory behavior such as periodic alternating nystagmus. The two models differ regarding the order of their VOR transfer function. Also, they predict different OKAN patterns following a prolonged optokinetic stimulus. These models have behavioral implications and suggest future experiments.     

Influence of the efferent vestibular system on vestibulo-spinal reflexes in the guinea pig

The influence of the efferent vestibular system on vestibulo-spinal activity was investigated during experiments on guinea pigs decerebrated and following cerebellar extirpation at precollincular level. Efferent vestibular neurons forming compact groups ventromedially to the vestibular nuclei were excited by means of electrical stimulation. Electromyographic activity in the triceps brachii extensor muscles of the right and left forelimbs was adopted as a test reaction (crossed extensor reflex and locomotor activity produced by stimulating the mesencephalic locomotor region). Adequate stimulation of the vestibular apparatus was accomplished by static tilting and cyclic shifting of the animal around its longitudinal axis at angles of ±20°. The efferent vestibular system was found to exert a bilateral inhibitory action on vestibulo-spinal activity. Vestibular efferent stimulation produced a reduction in the intensity of vestibulo-fugal influences: it does not change the dynamics of vestibulo-spinal reflex effects, however. Mechanisms of vestibular efferent action on vestibular control of spinal motor activity are discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 21, No. 1, pp. 78–86, January–February, 1989.     

Caloric Vestibular Stimulation Reduces Pain and Somatoparaphrenia in a Severe Chronic Central Post-Stroke Pain Patient: A Case Study

Central post-stroke pain is a neuropathic syndrome characterized by intolerable contralesional pain and, in rare cases, somatic delusions. To date, there is limited evidence for the effective treatments of this disease. Here we used caloric vestibular stimulation to reduce pain and somatoparaphrenia in a 57-year-old woman suffering from central post-stroke pain. Resting-state functional magnetic resonance imaging was used to assess the neurological effects of this treatment. Following vestibular stimulation we observed impressive improvements in motor skills, pain, and somatic delusions. In the functional connectivity study before the vestibular stimulation, we observed differences in the patient’s left thalamus functional connectivity, with respect to the thalamus connectivity of a control group (N = 20), in the bilateral cingulate cortex and left insula. After the caloric stimulation, the left thalamus functional connectivity with these regions, which are known to be involved in the cortical response to pain, disappeared as in the control group. The beneficial use of vestibular stimulation in the reduction of pain and somatic delusion in a CPSP patient is now documented by behavioral and imaging data. This evidence can be applied to theoretical models of pain and body delusions.     

Choline acetyltransferase immunoreactivity in the human vestibular end-organs

Acetylcholine (ACh) is believed to play a major role in the efferent vestibular system in several animal models, however no information regarding the role of ACh in the human efferent vestibular system has been published. Post-embedding immunohistochemistry in a hydrophilic resin was used to investigate the choline acetyltransferase immunoreactivity (ChATi) and acetylcholinesterase (ACHE) histochemistry in human vestibular end-organs. ChATi and AChE activity was found in numerous bouton-type terminals at the basal area of the vestibular hair cells. These terminals were found to contact type II vestibular hair cells and the afferent chalices surrounding type I hair cells. This study provides the first evidence that the human efferent vestibular axons and terminals are cholinergic.     

前庭电刺激联合前庭康复治疗周围性眩晕的疗效观察

目的：观察前庭电刺激联合前庭康复治疗周围性眩晕的疗效。方法：在常规药物治疗基础上将2008年5月．2012年5月我科眩晕门诊收治的226例诊断明确的单侧前庭周围性眩晕患者随机分成两组：前庭康复组和前庭康复＋前庭电刺激组。前庭康复组行常规前庭康复治疗,前庭康复＋前庭电刺激组在药物治疗及前庭康复基础上加用前庭电刺激,即在双侧乳突采取双极直流电刺激,每次15-20分钟,每天2次,共6周。治疗前及治疗后第2、4、6周行BBS评分及计时平衡试验时间测定以评判和比较两组的疗效。结果：两组患者治疗后第2、4、6周BBS评分及计时平衡试验时间较治疗前均明显增加（P〈0．05）,且B组各时点BBS评分及计时平衡试验时间均明显高于A组（P〈0．05）。结论：前庭电刺激联合前庭康复是较单纯前庭康复治疗前庭周围性眩晕更加有效的方法,其简单、无创、值得推广。     

Sensory processing in the vestibular nuclei during active head movements

Many secondary vestibular neurons are sensitive to head on trunk rotation during reflex-induced and voluntary head movements. During passive whole body rotation the interaction of head on trunk signals related to the vestibulo-collic reflex with vestibular signals increases the rotational gain of many secondary vestibular neurons, including many that project to the spinal cord. In some units, the sensitivity to head on trunk and vestibular input is matched and the resulting interaction produces an output that is related to the trunk velocity in space. In other units the head on trunk inputs are stronger and the resulting interaction produces an output that is larger during the reflex. During voluntary head movements, inputs related to head on trunk movement combine destructively with vestibular signals, and often cancel the sensory reafferent consequences of self-generated movements. Cancellation of sensory vestibular signals was observed in all of the antidromically identified secondary vestibulospinal units, even though many of these units were not significantly affected by reflexive head on trunk movements. The results imply that the inputs to vestibular neurons related to head on trunk rotation during reflexive and voluntary movements arise from different sources. We suggest that the relative strength of reflexive head on trunk input to different vestibular neurons might reflect the different functional roles they have in controlling the posture of the neck and body.     

Ultrastructural evidence of repair and neuronal survival after labyrinthectomy in the squirrel monkey

Although the vestibular and cochlear branches of the VIIIth cranial nerve originate embryologically from the same primordia, results of the present investigation confirm previous findings indicating that the vestibular branch may be more plastic with respect to recovery after surgical insult than the cochlear division. In this report we show ultrastructural details of changes undergone by the vestibular nerve after surgery. Dendrites peripheral to the vestibular nerve ganglion (VNG) were severed by surgically removing the vestibular end organs; the squirrel monkeys were then allowed to recuperate, and tested for their vestibulospinal and vestibulo-oculomotor functions behaviorally. However, behavior deficits resulting from the injury are reported separately. The vestibular nerves excised from the internal acoustic meatus and the temporal bones were examined histologically for changes of VNG and fibers from day 1 to 1,247 days after labyrinthectomy. Light- and electron-microscopic examinations indicated that some perikarya and some fibers of the VNG remained in the ganglionic matrix for up to 1,247 days, the longest period studied, after the operation. Fibers extended toward the remodeled inner ear space in the absence of appropriate sensory cell targets. The surviving neurons and fibers exhibited various degrees of wallerian-like degeneration at first, but many of them retained ultracellular organelles and integrity even after 1,247 days. Since vestibular perikarya are bipolar, the unsevered fibers that project to the brainstem could retain functional synaptic connections, a possibility that is now under investigation. Schwann cells in the ganglionic matrix may also have contributed to vestibular neuron survival by providing the proper nourishment. Morphometric measurements determined that neurons remaining in the ganglion had significantly smaller cross-sectional areas than normal neurons.(ABSTRACT TRUNCATED AT 250 WORDS)     

The convergent properties of the neocortical vestibular area in the cat]

In acute experiments on cats under nembutal-chloralose anaesthesia the evoked potentials and cellular reactions were studied of suprasylvian vestibular and auditory projection zones to stimulation of vestibular, acoustic and visual nerves and frontal paw. It has been shown that the suprasylvian vestibular zone represents the region of convergence of vestibular, auditory, somatic and visual afferentation. Properties of summary and cellular reactions of the vestibular zone and also the character of interaction of the evoked potentials of homo- and heteromodal origin testify to the absence of significant dominance of vestibular input to this area of the cerebral cortex in cats. Limitation of spreading of labyrinth activity in the cerebral cortex and the absence of dominance of homomodal input in the projection zone should, probably, be considered as typical property of the vestibular system presentation in the cortex, determining the disability of monomodal specific reaction in the sensory-perceptive sphere.     

Tonic conjugated action of receptor-receptor fibers and of the efferent vestibular system on the spontaneous afferene activity of a semicircular canal in the frog]

In the frog, the joint action of non-afferent vestibular systems [i.e. the efferent vestibular system and the receptor-receptor fibre system] on the afferent vestibular activity is null or very small. The receptor-receptor fibre system being inhibitory, it seems that the efferent vestibular system as a whole is facilitatory, which agrees with previous results.     

Spatial and temporal segregation of auditory and vestibular neurons in the otic placode

The otic placode generates the auditory and vestibular sense organs and their afferent neurons; however, how auditory and vestibular fates are specified is unknown. We have generated a fate map of the otic placode and show that precursors for vestibular and auditory cells are regionally segregated in the otic epithelium. The anterior-lateral portion of the otic placode generates vestibular neurons, whereas the posterior-medial region gives rise to auditory neurons. Precursors for vestibular and auditory sense organs show the same distribution. Thus, different regions of the otic placode correspond to particular sense organs and their innervating neurons. Neurons from contiguous domains rarely intermingle suggesting that the regional organisation of the otic placode dictates positional cues to otic neurons. But, in addition, vestibular and cochlear neurogenesis also follows a stereotyped temporal pattern. Precursors from the anterior-lateral otic placode delaminate earlier than those from its medial-posterior portion. The expression of the proneural genes NeuroM and NeuroD reflects the sequence of neuroblast formation and differentiation. Both genes are transiently expressed in vestibular and then in cochlear neuroblasts, while differentiated neurons express Islet1, Tuj1 and TrkC, but not NeuroM or NeuroD. Together, our results indicate that the position of precursors within the otic placode confers identity to sensory organs and to the corresponding otic neurons. In addition, positional information is integrated with temporal cues that coordinate neurogenesis and sensory differentiation.     

Aging in the vestibular nuclear complex of the male golden hamster (Mesocricetus auratus): anatomic and morphometric study

To study the effects of senescence on the vestibular nuclear complex twenty brainstems from male golden hamsters between 3 and 27 months-old were used and the possible variations in the number of neurons, neuronal morphology and nuclear volume were studied. The neuron profiles were drawn with a camera lucida and Abercrombie's method was used to estimate the total number of neurons. The test of Kolmogorov-Smirnov with the correction of Lilliefors was used to evaluate the fit of our data to a normal distribution and a regression analysis was done to decide if the variation of our data with age was statistically significant. The results of the present study are relevant only for male animals and the effect of senescence could be different in female vestibular nuclear complex. Aging affects the volume of the superior and lateral vestibular nuclei, as well as the nuclear neuronal diameter of the medial vestibular nucleus, but no significant neuronal loss has been appreciated in vestibular nuclear complex related with age. During the aging process we have observed that the distribution of neurons within the vestibular nuclei of the golden hamster does not show important changes and most of their morphometric parameters do not vary significantly.     

Preliminary observations on the morphology of the inner ear of the fetal narwhal (Monodon monoceros)

The inner ear of the narwhal (Monodon monoceros) was investigated on the basis of a complete series of microslides of an early fetus. In this well‐preserved specimen, the cochlea is about twice as large as the vestibular apparatus. The latter exhibits a high degree of specialization. Whereas the utriculus and sacculus are of normal size in comparison with those of other mammals, the semicircular canals are miniaturized but not obliterated, as in the case of some adult toothed whales. In comparison with other mammals, there is relatively little perilymphatic space around the vestibular organ, but the inner radius of the lymphatic ducts comes close to that of the adult human. Although there are some hints that the sensitivity of the vestibular system may be high in this species, detailed analysis of the adult narwhal ear is needed to confirm this inference.     

Light microscopical observation of infraciliary bands of Eodinium posterovesiculatum in comparison with Entodinium bursa and Diplodinium dentatum

Morphological features of the four morphotypes of the rumen ciliate, Eodinium posterovesiculatum, are described from pyridinated silver carbonate-impregnated specimens. Infraciliary bands are compared with those of Entodinium bursa and Diplodinium dentatum. In Entodinium bursa, the adoral polybrachykinety is "C" shaped and the vestibular polybrachykinety extends from the dorsal extremity of the adoral polybrachykinety as in other Entodinium species. In Diplodinium dentatum, the adoral polybrachykinety encircles most of the circumference of the vestibular opening and the vestibular polybrachykinety extends from the inner side of the adoral polybrachykinety as in other Diplodinium species. Infraciliary bands in Eodinium posterovesiculatum encircle the whole circumference of the vestibular opening and are, therefore, distinct from Entodinium, Diplodinium and other ciliates in the family Ophryoscolecidae. In Eodinium posterovesiculatum, the adoral polybrachykinety and the anterior part of the vestibular polybrachykinety encircle the vestibular opening. The wide and long vestibular polybrachykinety extends along the right wall of the tubular vestibulum and is bordered by a kinety. Kinetids in the central part of the vestibular polybrachykinety are randomly disposed. The genus Eodinium is valid because of this characteristic polybrachykinety arrangement in Eodinium posterovesiculatum.     

A neural network simulation of the vestibular system: implications on the role of intervestibular nuclear coupling during vestibular compensation

 Previous neural network simulations of the vestibular system have been based loosely on known physiology. This research involved the use of a strongly physiologically based neural network model which was used to investigate the role of the vestibular commissure in restoring the bilateral symmetry of the resting rates of the vestibular nuclei during vestibular compensation following unilateral labyrinthectomy. It was found that readjustments in the gain of the vestibular commissure were not primarily responsible for vestibular compensation, as has previously been suggested, but rather that it was modifications in extralabyrinthine sources of tone which mediated the restoration of the central symmetry between the two nuclei. Received: 20 November 1995/Accepted in revised form: 24 July 1996     

Functional characteristics of the input-output correlation in the frog vestibular nuclei

Field and intracellular potentials were recorded in the vestibular nuclear complex of the frog perfused brain following stimulation of the anterior branch of the ipsilateral vestibular nerve and spinal cord. Mono- and polysynaptic EPSPs with orthodromic APs were recorded from vestibular neurones following vestibular nerve stimulation. Antidromic activation of neurones sending their axons to the labyrinth was also recorded. Antidromic APs of vestibulo-spinal neurones evoked with mean latency of 1.43 and 2.19 ms to stimulation of cervical and lumbar cords, respectively, were revealed.     

Bilateral otolith contribution to spatial coding in the vestibular system

Recent work on the coding of spatial information in central otolith neurons has significantly advanced our knowledge of signal transformation from head-fixed otolith coordinates to space-centered coordinates during motion. In this review, emphasis is placed on the neural mechanisms by which signals generated at the bilateral labyrinths are recognized as gravity-dependent spatial information and in turn as substrate for otolithic reflexes. We first focus on the spatiotemporal neuronal response patterns (i.e. one- and two-dimensional neurons) to pure otolith stimulation, as assessed by single unit recording from the vestibular nucleus in labyrinth-intact animals. These spatiotemporal features are also analyzed in association with other electrophysiological properties to evaluate their role in the central construction of a spatial frame of reference in the otolith system. Data derived from animals with elimination of inputs from one labyrinth then provide evidence that during vestibular stimulation signals arising from a single utricle are operative at the level of both the ipsilateral and contralateral vestibular nuclei. Hemilabyrinthectomy also revealed neural asymmetries in spontaneous activity, response dynamics and spatial coding behavior between neuronal subpopulations on the two sides and as a result suggested a segregation of otolith signals reaching the ipsilateral and contralateral vestibular nuclei. Recent studies have confirmed and extended previous observations that the recovery of resting activity within the vestibular nuclear complex during vestibular compensation is related to changes in both intrinsic membrane properties and capacities to respond to extracellular factors. The bilateral imbalance provides the basis for deranged spatial coding and motor deficits accompanying hemilabyrinthectomy. Taken together, these experimental findings indicate that in the normal state converging inputs from bilateral vestibular labyrinths are essential to spatiotemporal signal transformation at the central otolith neurons during low-frequency head movements.