Evidence against a role of gap junctions in vestibular compensation.

Vestibular compensation following unilateral labyrinthectomy is associated with modifications of the membrane and firing properties of central vestibular neurons. To determine whether gap junctions could be involved in this process, immunofluorescent detection of neuronal connexin 36 and astrocytic connexin 43 was performed in the medial vestibular nucleus (MVN) of rats. In non-lesioned animals, strong staining was observed with anti-connexin 43 antibodies, while moderate staining was obtained with the anti-connexin 36 antibody. However, the expression of either type of connexin was not modified following unilateral labyrinthectomy. These morphological observations were complemented by pharmacological tests performed during extracellular recordings of MVN neurons in guinea pig brainstem slices. In non-lesioned animals, the gap junction blocker carbenoxolone reversibly decreased or suppressed the spontaneous discharge of about 60% of MVN neurons. This reduction was often associated with a long-duration disruption of the regularity of spike discharge. Both effects were mimicked by several other gap junction blockers, but not by glycyrrhizic acid, an analog of carbenoxolone that does not block gap junctions but reproduces its non-specific effects, nor by the selective inhibitor of astrocytic connexin-based networks endothelin-1. Similar effects of carbenoxolone were obtained on the spontaneous activity of ipsilesional MVN neurons recorded in brainstem slices taken from labyrinthectomized animals. Altogether, these results suggest that neuronal gap junctions are involved in shaping the spontaneous activity of MVN neurons. However, unilateral labyrinthectomy does not affect the expression of gap junctions in vestibular nuclei nor their implication in the regulation of neuronal activity.

Role of vestibular input in triggering and modulating postural responses in unilateral and bilateral vestibular loss patients.

The aim of this study was to determine whether the greater medial-lateral (ML) instability observed in patients with compensated unilateral vestibular loss (UVL), tested on a seesaw platform with eyes closed, is task-dependent. UVL patients, categorized into three groups according to time since lesion (1 week, 1 month and 1 year), bilateral vestibular loss patients and age-matched healthy control subjects were tested in three dynamic postural tasks. These tasks involved different supports - a seesaw platform (Satel), a platform generating horizontal linear translations (Synapsys) and foam rubber placed on a static platform - each requiring different somatosensory cues to maintain equilibrium. Displacements of the subjects' center of pressure in both the anterior-posterior (AP) and ML directions were recorded by strain gauges within the platforms. Only tests performed with eyes closed were analyzed. Bilateral vestibular loss patients fell during foam and seesaw trials but not on the platform generating translations. We previously reported that UVL patients had greater postural oscillations on the seesaw platform in the ML compared to AP direction. In this study, we show similar ML/AP differences in patient performance on foam when standing with 'feet close together'. In contrast, these differences were not found when patients were tested on linear translation or on foam standing with feet apart. In conclusion, the postural performance of patients with vestibular loss depends on the exact task used to measure postural stability. UVL patients are less stable when subjected to movement in the ML direction because of the biomechanical constraints of the tasks and/or the availability of proprioceptive information.

[Skull vibration induced nystagmus test]. / Le test vibratoire osseux vestibulaire.

OBJECTIVES: To establish during a consensus meeting the fundamental basis, the validity criteria, the main indications and results of the skull vibration induced nystagmus test (SVINT) which explores the vestibule high frequencies. MATERIAL AND METHODS: The SVINT is applied on the mastoid process (right and left sides) at 100 Hz during 10 seconds on a sitting upright subject. Total unilateral peripheral lesions (tUVL: operated vestibular shwannomas, vestibular neurectomies) and partial unilateral peripheral lesions (pUVL: preoperative neuromas, Meniere's disease, vestibular neuritis, chemical labyrinthectomies) were studied. Thirty-six patients had brainstem lesions and 173 normal subjects were used as controls. RESULTS: The SVINT is considered positive when the application of the vibrator produces a reproducible sustained nystagmus always beating in the same direction following several trials in various stimulation topographies (on the right and left mastoid). The skull vibratory nystagmus (SVN) begins and ends with the stimulation; the direction of the nystagmus has no secondary reversal. The slow phase velocity (SPV) is>2 degrees /second. In tUVL the SVINT always reveals a lesional nystagmus beating toward the safe side at all frequencies. The mean SVN SPV is 10.8 degrees /s+/-7.5 SD (N=45). The mastoid site was more efficient than the cervical or vertex sites. Mastoïd stimulation efficiency is not correlated with the side of stimulation. The SVN SPV is correlated with the total caloric efficiency on the healthy ear. In pUVL the SVINT is positive in 71 to 76% of cases; the mean SVN. SPV (6.7 degrees /s+/-4.7 SD)(N=30) is significantly lower than in tUVL (P=0.0004). SVINT is positive in 6 to 10% of the normal population, 31% of brain stem lesions and negative in total bilateral vestibular peripheral lesions. CONCLUSIONS: SVINT is an effective, rapid and non invasive test used to detect vestibular asymmetry between 20 to 150 Hz stimulation. This test used in important cohorts of patients during the ten last years has demonstrated no observable adverse effect. SVINT complements other tests which evaluate lower frequencies (caloric test: 0,003 Hz) and the medium frequencies (Head-Shaking-Test (HST): 2 Hz; the head impulse test (HIT): 6 Hz). SVINT is useful in the diagnosis of labyrinthine hydrops or detection of acoustic neuromas. It is useful when the caloric test can not be practised because of middle ear problems. SVINT has its limits: in pUVL, the nystagmus direction is not always specific of the pathologic side and can change with the stimulus frequency. This test does not precisely point out the level of the lesion on the vestibular pathway.

Modulation of inhibitory and excitatory synaptic transmission in rat inferior colliculus after unilateral cochleectomy: an in situ and immunofluorescence study.

We investigated whether inhibitory synaptic transmission mediated through glycinergic receptor, GABAA receptors, glutamic acid decarboxylase, the enzyme synthesizing GABA, and excitatory synaptic transmission through alpha-amino-3-hydroxi-5-methylisoxazole-4-propionic acid receptors and N-methyl-D-aspartate receptors are affected in the inferior colliculus by unilateral surgical cochleectomy. In situ hybridization and immunohistofluorescence studies were performed in normal and lesioned adult rats at various times following the lesion (1-150 days). Unilateral auditory deprivation decreased glycine receptor alpha1 and glutamic acid decarboxylase 67 expression in the contralateral central nucleus of the inferior colliculus. This decrease began one day after cochleectomy, and continued until day 8; thereafter expression was consistently low until day 150. The glycine receptor alpha1 subunit decrease did not occur if a second contralateral cochleectomy was performed either on day 8 or 150 after the first cochleectomy. Bilateral cochleectomy caused also a bilateral inferior colliculus diminution of glutamic acid decarboxylase 67 mRNA at post-lesion day 8 but there were no changes in glycine receptor alpha1 compared with controls. In contrast, the abundance of other alpha2-3, and beta glycine receptor, gephyrin, the anchoring protein of glycine receptor, the alpha1, beta2 and gamma2 subunits of GABAA receptors, GluR2, R3 subunits of alpha-amino-3-hydroxi-5-methylisoxazole-4-propionic acid receptors, and NR1 and NR2A transcripts of N-methyl-D-aspartate receptors was unaffected during the first week following the lesion. Thus, unilateral cochlear removal resulted in a selective and long-term decrease in the amount of the glycine receptor alpha1 subunit and of glutamic acid decarboxylase 67 in the contralateral central nucleus of the inferior colliculus. These changes most probably result from the induced asymmetry of excitatory auditory inputs into the central nucleus of the inferior colliculus and may be one of the mechanisms involved in the tinnitus frequently encountered in patients suffering from a sudden hearing loss.

The vestibular system as a model of sensorimotor transformations. A combined in vivo and in vitro approach to study the cellular mechanisms of gaze and posture stabilization in mammals.

To understand the cellular mechanisms underlying behaviours in mammals, the respective contributions of the individual properties characterizing each neuron, as opposed to the properties emerging from the organization of these neurons in functional networks, have to be evaluated. This requires the use, in the same species, of various in vivo and in vitro experimental preparations. The present review is meant to illustrate how such a combined in vivo in vitro approach can be used to investigate the vestibular-related neuronal networks involved in gaze and posture stabilization, together with their plasticity, in the adult guinea-pig. Following first a general introduction on the vestibular system, the second section describes various in vivo experiments aimed at characterizing gaze and posture stabilization in that species. The third and fourth parts of the review deal with the combined in vivo-in vitro investigations undertaken to unravel the physiological and pharmacological properties of vestibulo-ocular and vestibulo-spinal networks, together with their functional implications. In particular, we have tried to use the central vestibular neurons as examples to illustrate how the preparation of isolated whole brain can be used to bridge the gap between the results obtained through in vitro, intracellular recordings on slices and those collected in vivo, in the behaving animal.

Modulation of the glutamatergic receptors (AMPA and NMDA) and of glutamate vesicular transporter 2 in the rat facial nucleus after axotomy.

Facial nerve axotomy is a good model for studying neuronal plasticity and regeneration in the peripheral nervous system. We investigated in the rat the effect of axotomy on the different subunits of excitatory glutamatergic AMPA (GLuR1-4), NMDA (NR1, NR2A-D) receptors, post-synaptic density 95, vesicular glutamate transporter 2, beta catenin and cadherin. mRNA levels and/or protein production were analyzed 1, 3, 8, 30 and 60 days after facial nerve axotomy by in situ hybridization and immunohistofluorescence. mRNAs coding for the GLuR2-4, NR1, NR2A, B, D subunits of glutamatergic receptors and for post-synaptic density 95, were less abundant after axotomy. The decrease began as early as 1 or 3 days after axotomy; the mRNAs levels were lowest 8 days post-lesion, and returned to normal or near normal 60 days after the lesion. The NR2C subunit mRNAs were not detected in either lesioned or intact facial nuclei. Immunohistochemistry using specific antibodies against GLuR2-3 subunits and against NR1 confirmed this down-regulation. There was also a large decrease in vesicular glutamate transporter 2 immunostaining in the axotomized facial nuclei at early stages following facial nerve section. In contrast, no decrease of NR2A subunit and of post-synaptic density 95 could be detected at any time following the lesion. beta Catenin and cadherin immunoreactivity pattern changed around the cell body of facial motoneuron by day 3 after axotomy, and then, tends to recover at day post-lesion 60 days. Therefore, our results suggest a high correlation between restoration of nerve/muscle synaptic contact, synaptic structure and function in facial nuclei. To investigate the mechanisms involved in the change of expression of these proteins following axotomy, the facial nerve was perfused with tetrodotoxin for 8 days. The blockade of action potential significantly decreased GLuR2-3, NR1and NR2A mRNAs in the ipsilateral facial nuclei. Thus, axotomy-induced changes in mRNA abundance seemed to depend partly on disruption of activity.

The differential response of astrocytes within the vestibular and cochlear nuclei following unilateral labyrinthectomy or vestibular afferent activity blockade by transtympanic tetrodotoxin injection in the rat.

In this study, we investigated whether changes in the vestibular neuronal activity per se influence the pattern of astrocytes morphology, glial fibrillary acidic protein (GFAP) expression and ultimately their activation within the vestibular nuclei after unilateral transtympanic tetrodotoxin (TTX) injections and after unilateral inner ear lesion. The rationale was that, theoretically the noninvasive pharmacological functional blockade of peripheral vestibular inputs with TTX, allowed us to dissociate the signals exclusively related to the shutdown of the resting activity of the first-order vestibular neurons and from neuronal signals associated with trans-ganglionic changes in first order vestibular neurons induced by unilateral labyrinthectomy (UL). Since the cochlea was removed during the surgical procedure, we also studied the astrocytic reaction within the deafferented cochlear nuclei. No significant changes in the distribution or relative levels of GFAP mRNA expression, relative levels of GFAP protein or immunoreactivity for GFAP were found in the ipsilateral vestibular nuclei at any post-TTX injection times studied. In addition, no sign of microglia activation was observed. In contrast, a robust increase of the distribution and relative levels of GFAP mRNA expression, protein levels and immunoreactivity was observed in the deafferented vestibular and cochlear nuclei beginning at 1 day after inner ear lesion. GFAP mRNA expression and immunoreactivity in the cochlear nucleus was qualitatively stronger than in the ipsilateral vestibular nuclei. The results suggest that astrocyte activation in the vestibular nuclei is not related to drastic changes of vestibular nuclei neuronal activity per se. Early trans-ganglionic changes due to vestibular nerve dendrites lesion provoked by the mechanical destruction of vestibular receptors, most probably induced the glial reaction. Its functional role in the vestibular compensation process remains to be elucidated.

Excitatory amino acid receptors in normal and abnormal vestibular function.

Although excitatory amino acid (EAA) receptors have been investigated extensively in the limbic system and neocortex, less is known of the function of EAA receptors in the brainstem. A number of biochemical and electrophysiological studies suggest that the synapse between the ipsilateral vestibular (VIIIth) nerve and the brainstem vestibular nucleus (VN) is mediated by an EAA acting predominantly on kainate or alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors. In addition, there is electrophysiological evidence that input from the contralateral vestibular nerve via the contralateral VN is partially mediated by N-methyl-D-aspartate (NMDA) receptors. Input to the VN from the spinal cord may also be partially mediated by NMDA receptors. All of the electrophysiological studies conducted so far have used in vitro preparations, and it is possible that denervation of the VN during the preparation of an explant or slice causes changes in EAA receptor function. Nonetheless, these results suggest that EAA receptors may be important in many different parts of the vestibular reflex pathways. Studies of the peripheral vestibular system have also shown that EAAs are involved in transmission between the receptor hair cells and the vestibular nerve fibers. A number of recent studies in the area of vestibular plasticity have reported that antagonists for the NMDA receptor subtype disrupt the behavioral recovery that occurs following unilateral deafferentation of the vestibular nerve fibers (vestibular compensation). It has been suggested that vestibular compensation may be owing to an upregulation or increased affinity of NMDA receptors in the VN ipsilateral to the peripheral deafferentation; however; at present, there is no clear evidence to support this hypothesis.

Cochlear electrical stimulation: influence of age of implantation on Fos immunocytochemical reactions in inferior colliculi and dorsal cochlear nuclei of the rat.

The influence of age at the time of implantation of a stimulating electrode unilaterally in the inner ear on central auditory pathways was investigated in rats deafened shortly after birth. Immunoreactivity for Fos served as a functional marker of neuronal activity. Electrodes were implanted in the left cochlea of rats aged 3 weeks or 4 months. Stimulation lasted 45 minutes, then rats were sacrificed and tissues processed for immunocytochemistry. The younger animals showed significantly more neurons with Fos immunoreactivity bilaterally in the dorsal cochlear nuclei (DCN) and inferior colliculi (IC) than the older rats or control animals with normal hearing receiving the same stimulation. Activity was more prominent in the left DCN and right IC. The results show that electrical stimulation of the inner ear is more effective in younger animals in eliciting gene expression associated with development of a functional network in the auditory pathways. This suggests that deaf children should be provided with cochlear implants as early as possible.

Intratympanic gentamicin injections for Meniere disease: vestibular hair cell impairment and regeneration.

The authors treated 22 patients with intratympanic gentamicin. Vestibular function was measured using caloric and head impulse tests and vestibular evoked myogenic potentials induced by high amplitude sounds and short duration galvanic currents. Roughly one-third of the patients, after initially losing their caloric responses and displaying refixation saccades to head impulse tests, recovered within 2 years of the lesion. Vertigo did not recur in patients in whom the galvanic response was abolished.

GluR2-R4 AMPA subunit study in rat vestibular nuclei after unilateral labyrinthectomy: an in situ and immunohistochemical study.

In the present investigation, we address the question of whether the expression of GluR2-R4 subunits mRNAs and GluR2 and GluR4 subunits protein of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-selective glutamate receptors are modulated in the vestibular nuclei following unilateral labyrinthectomy. Specific GluR2-R4 radioactive oligonucleotides were used to probe sections of rat vestibular nuclei according to in situ hybridization methods. The signal was detected by means of film or emulsion photography. GluR2 and GluR4 subunit expression were also measured in control and operated rats by use of specific monoclonal GluR2 and GluR4 antibodies. Animals were killed at different stages following the lesion: 1, 3 or 8 days for the in situ hybridization study and 4 and 8 days for the immunohistochemical study. In normal animals, several brainstem regions including the lateral, medial, superior and inferior vestibular nuclei expressed all the GluR2, GluR3 and GluR4 subunit mRNAs. Moreover, numerous vestibular nuclei neurons are endowed with AMPA receptors containing the GluR2 and the GluR4 subunits. In unilaterally labyrinthectomized rats, no asymmetry could be detected on autoradiographs between the two medial vestibular nuclei probed with the GluR2 and the GluR4 oligonucleotide probes regardless of the delay following the lesion. However, compared to control, a bilateral decrease (-22%) in GluR3 gene expression was observed in the medial vestibular nuclei 3 days after the lesion followed by a return to normal at day 8 post-lesion. No significant asymmetrical changes in the density of GluR2- and GluR4-immunopositive cells could be detected between the intact and deafferented sides in any part of the vestibular nuclear complex and at any times (day 4 or day 8) following the lesion. Our data show that the removal of glutamatergic vestibular input induced an absence of modulation of GluR2 and GluR4 gene and subunits expression. This demonstrates that GluR2 and GluR4 expression do not play a role in the recovery of the resting discharge of the deafferented medial vestibular nuclei neurons and consequently in the functional restoration of the static postural and oculomotor deficits. The functional role of the slight and bilateral GluR3 mRNA decrease in the vestibular nuclei remains to be elucidated.

Modulation of the voltage-gated sodium- and calcium-dependent potassium channels in rat vestibular and facial nuclei after unilateral labyrinthectomy and facial nerve transsection: an in situ hybridization study.

We investigated whether the expression in the vestibular and facial nuclei of the voltage-dependent Na alpha I and Na alpha III channels and of the Ca(2+)-activated K(+)-channel subunits, small-conductance (SK) 1, SK2 and SK3, is affected by unilateral inner-ear lesion including both labyrinthectomy and transsection of the facial nerve. Specific sodium (Na alpha I, Na alpha III) and potassium (SK1, SK2, SK3) radioactive oligonucleotides were used to probe sections of rat vestibular and facial nuclei by in situ hybridization methods. The signal was detected with films or by emulsion photography. Animals were killed at various times following the lesion: 1 day, 3 days, 8 days or 30 days. In normal adult animals, mRNAs for Na alpha I, and SK1, SK2, and SK3 channels were found in several brainstem regions including the lateral, medial, superior and inferior vestibular nuclei and the facial nuclei. In contrast, there was little Na alpha III subunit mRNA anywhere in the brainstem. Following unilateral inner ear lesion in rats, the medial vestibular nuclei were probed with Na alpha I, Na alpha III, SK1, SK2 and SK3 oligonucleotide probes: autoradiography indicated no difference between the two sides, at any of the times studied. Na alpha I and SK2 mRNAs were less abundant and Na alpha III, SK1 and SK3 mRNAs were more abundant in the axotomized facial nuclei motoneurons than in controls. Removal of vestibular input did not affect the abundance of the mRNAs for the sodium- or calcium-dependent potassium channels in the deafferented vestibular nuclei. There is thus no evidence that modulation of these conductances contributes to the recovery of a normal resting discharge of the deafferented vestibular neurons and consequently to the functional recovery of the postural and oculomotor deficits observed at the acute stage. However, facial axotomy induced a long-term modulation of both Na and SK conductances mRNAs in the facial motoneurons ipsilateral to the lesion. Presumably, retrograde injury factors resulting from axotomy were able to alter durably the membrane properties and thus the excitability of the facial motoneurons.

Evidence for a microglial reaction within the vestibular and cochlear nuclei following inner ear lesion in the rat.

Following unilateral inner ear lesion, astrocytes undergo hypertrophy in the deafferented vestibular and cochlear nuclei as shown by an increase in the level of glial fibrillary acid. The present study extends our understanding of vestibular and cochlear system plasticity by examining microglial changes in these deafferented nuclei. The microglial reaction was studied 1, 2, 4, 8, 14, 21, 28 and 42 days following the lesion with a monoclonal OX-42 antibody and lectins (Griffonia simplicifolia, B4 isolectin) labelled with horseradish peroxidase or fluorescein. The deafferented nuclei were also examined for apoptotic cells by terminal transferase-mediated nick end labelling of nuclear DNA fragments. In control and sham-operated rats, the distribution of the resting microglial cells was uniform in both the vestibular and cochlear nuclei. In the deafferented vestibular complex, the microglial cells increased in number, became hypertrophied and were distributed in the medial, lateral, superior and inferior vestibular nuclei. Reactive microglial cells were also detected in the ipsilateral cochlear nuclei. Some of the immunostained cells were hypertrophic whereas others presented an ameboid morphology with few short and stout processes. The microglial reaction was confined to the antero- and posteroventral cochlear nuclei. Finally, reactive microglia was also observed in the prepositus hypoglossi ipsilateral to the lesion. The microglial reactions within the prepositus hypoglossi, the vestibular and the cochlear nuclei were detectable as early as one day after the lesion and persisted several weeks in both the vestibular and cochlear nuclei. Apoptotic cells were not detected in the vestibular nuclei at any stage following the lesion. In contrast, terminal deoxynucleotidyl transferase-mediated digoxygenin-11-dUTP nick end labelling-positive cells were first detected in the deafferented cochlear nuclei on the 3rd day following the lesion. They reached an apparent maximum by day 8 and then declined until day 24. Double labelling experiments demonstrate that these cochlear terminal deoxynucleotidyl transferase-mediated digoxygenin-11-dUTP nick end labelling-positive cells were also lectin-positive suggesting that reactive cochlear lectin-positive microglia cells were eliminated by a programmed cell death. Our results establish the two experimental models as reliable tools to understand the role of microglia in adult brain plasticity. The cochlear microglial reaction was probably induced by the degeneration of the acoustic nerve which follows the acoustic ganglion destruction. Interestingly, the same reasoning cannot apply to the vestibular microglial reaction following unilateral labyrinthectomy: the vestibular ganglion was spared and the primary vestibular neurons did not degenerate, at least during the first week following the lesion.

Modulation of the beta1-3 voltage-gated sodium channels in rat vestibular and facial nuclei after unilateral labyrinthectomy and facial nerve section: an in situ hybridization study.

We investigated whether the production of the mRNAs for the auxiliary beta subunits of the Na channels are modulated in deafferented medial vestibular nucleus (MVN) and in axotomized facial motoneurons. No beta1-3 mRNAs modulation was detected at any time following unilateral labyrinthectomy in the deafferented and intact medial vestibular nucleus. In contrast, beta1 gene expression in the axotomized facial nucleus decreased compared to controls as soon as day post-lesion 3.

Vestibular control of skeletal geometry in the guinea pig: a problem of good trim?

Motor control of different segments of the body with multiple degrees of freedom appears to be coordinated by utilizing preferred axes of motor activity. This hypothesis may also be applied to vestibular control of posture. To explore this question we studied the anatomical relationship between the head and the cervical vertebral column by taking radiographs of the head-neck region in unrestrained alert guinea pigs. We determined that biomechanical constraints contribute to the stereotypical skeletal geometry observed in the resting animal and to a functional segmentation of the head-neck movement apparatus. Subsequent lesion studies of vestibular end organs with quantification of the resulting postural syndromes suggest that the functional segmentation of the cervical vertebral column corresponds to a functional partitioning of vestibular afferents. Our findings also indicate that the sensorimotor transformation mechanisms necessary to convert a given head velocity signal into the appropriate neck motor frame are already embedded in the networks provided by second-order vestibular neurons. Good trim of postural control will be the end result of an appropriate internal representation of the objective vertical.

Effect of post-training unilateral labyrinthectomy in a spatial orientation task by guinea pigs.

The effects of unilateral labyrinthectomy in guinea pigs have been studied on an angular orientation task consisting, in an open field, of running to a hidden goal oriented at 45 degrees with respect to the cephalocaudal axis of the animal placed in a starting-box. The task was conducted in light but in an homogeneous environment, i.e. without visual, auditory or olfactory cues indicating the location of the goal. A second group of animals was submitted to a similar task running to a hidden goal but the place of the goal was indicated by a colored card. All the animals were trained before the lesion and tested in their respective task for 1 month after the lesion. In the task conducted without conspicuous cues, animals were dramatically disturbed. In contrast, animals pretrained in the visually guided task were not impaired after the lesion. These results point out the important role of vestibular information in performing spatial tasks based on angular estimation, since, even if proprioceptive and visuokinesthetic information remain available, subjects seemed not able to maintain a correct angular trajectory. The trajectories being not disturbed in the visually guided task, one can exclude the hypothesis that such deficit was due to a purely motor disturbance.

Glycinergic inhibition of spontaneously active guinea-pig medial vestibular nucleus neurons in vitro.

Effects of glycine on the spontaneous activity of medial vestibular nucleus (MVN) neurons recorded extracellularly from guinea-pig brainstem slices were investigated. Glycine produced a dose-dependent decrease in the resting discharge rate of all MVN neurons tested, with a mean EC50 of 3.9 x 10(-4) M. The inhibitory effect of glycine was reversibly blocked by strychnine and persisted in a low calcium/high magnesium-containing saline solution. These findings suggest the existence of a direct strychnine-sensitive inhibitory effect of glycine on guinea-pig MVN neurons.

NMDA receptors of the vestibular nuclei neurones.

Cloning and pharmacological studies have shown that glutamatergic receptors can be divided in two classes (refer to Table 1): ionotropic receptors including N-methyl-D-aspartate (NMDA) and non-NMDA subtypes, and the G-protein-coupled metabotropic receptors (glutamate metabotropic receptor). There are two types of non-NMDA receptors: the AMPA/low-affinity kainate receptor type (the AMPA receptors) activated by a specific agonist, the alpha-amino-3-hydroxy-5-methyl-4-iso-xalone propionate (AMPA), and the high affinity kainate receptors. The vestibular nuclei neurones are endowed with all these types of glutamatergic receptors, which fits well with the fact that various afferents, including the primary vestibular afferents, most probably use glutamate or aspartate as a neurotransmitter. This article is aimed at summarising several past studies of our group and some more recent data obtained in the in vitro whole-brain preparation concerning the NMDA receptors of the central vestibular neurones. In that process, we will detail also many valuable studies of other groups that had been devoted to the same topic.

Vestibular compensation revisited.

Vestibular compensation for the static and dynamic disorders induced by unilateral labyrinthectomy is a good model of plasticity in the central nervous system. After the lesion, the static deficits generally disappear in a few days, whereas recuperation of the dynamic, vestibular-related synergies is much slower and merely partial. The goal of this article is to reexamine some aspects of vestibular compensation in light of several recent findings. In the first part, we show that in vertebrates the organization of the neural networks underlying vestibular reflexes is deeply linked with the skeletal geometry of the animals. Accordingly, we propose that the neuronal mechanisms underlying vestibular compensation might be plane specific. We then deal with several issues related to the exact timing of vestibular compensation in various species. In the second part, we give several examples showing that vestibular compensation can now be studied at the molecular and cellular levels. For instance, we summarize some of our recent data, which indicate that glial cells could be strongly involved in the compensation process.

[D-penicillamine in the treatment of recurrent laryngeal stenosis in children]. / La D. penicillamine dans le traitement des stenoses laryngées récidivantes de l'enfant.

Five children with recurrent tracheal stenosis after use of an endolaryngeal calibrator and/or a laryngoplasty were treated with D-penicillamine and chloroquine. The relevant literature relating to biological processes of normal and pathologic healing is reviewed, particularly with respect to the effect of D-penicillamine on collagen synthesis. Decannulation was possible in 4 of the children reported presently, including three in whom medical treatment was combined with use of an endolaryngeal calibrator.