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C de Waele

Publications and source records attributed to C de Waele.

At least 37 records · Page 2Linked to original sources

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.

Animals↗

Evidence for reactive astrocytes in rat vestibular and cochlear nuclei following unilateral inner ear lesion.

We investigated whether unilateral removal of the labyrinthine and cochlear receptors induces a macroglial reaction in rat vestibular and cochlear nuclei using vimentin and glial fibrillary acidic protein (GFAP) immunochemical markers. Antibody binding was visualized using the avidin-biotin method and 3,3'-diaminobenzidine as the peroxidase substrate. In addition, double-labelling experiments were performed using specific secondary fluorescent antibodies. Potentially degenerating axon terminals were also studied using a silver impregnation method. In normal adult rats, vimentin was found only in ependymal cells, tanicytes around the fourth ventricle, endothelial cells in the blood vessels and Bergmann glia in the molecular layer of the cerebellum. In lesioned rats, all deafferented vestibular and ventral cochlear nuclei showed strong vimentin immunoreactivity. Furthermore, double-labelling experiments demonstrated that these vimentin-positive cells were also GFAP-positive. The reaction became evident on the second day after the lesion, was intense for 3-8 days and then declined until day 21. No vimentin immunoreactivity could be detected at the level of the ipsilateral dorsal cochlear nucleus. Therefore, unilateral inner ear lesion induced an astroglial reaction within the deafferented vestibular and cochlear nuclei. The decrease in the resting discharge of the primary vestibular afferents and/or in the deafferented central vestibular neurons may induce the glial reaction in the vestibular complex, whereas both degeneration and silence of the cochlear nerve and central cochlear neurons are most probably responsible for the cochlear vimentin-immunoreactive staining. The role of the reactive astrocytes in the vestibular compensation process remains to be determined.

Animals↗

Neurochemistry of the central vestibular pathways.

This review focuses on the neurochemistry of the central vestibular pathways. The main emphasis will be on the analysis of the central vestibular nuclei neurons, since several papers published in the past 5 years have provided important information on the role that neurotransmitter-dependent conductances play in the central processing of vestibular inputs. Indeed, increasing evidence suggests that both the non-linear intrinsic membrane properties of the neurons and the nature of the different neurotransmitters and neuromodulators involved in the vestibular network contribute to the various operations required for stabilising gaze and posture. It has also been demonstrated that the neurotransmitter-dependent conductances together with the ionic voltage-dependent conductances may determine the firing patterns of the medial vestibular neurons and interfere with their integrative properties. We hope that this review will show that by combining in vitro and in vivo electrophysiological approaches and the new powerful neuropharmacological techniques developed from the recent advances of molecular biology, the vestibular system can be used as a good model to elucidate some of the basic properties of the brain including learning, neural computation, network reconfiguration and post-lesional plasticity.

Acetylcholine↗

Neuronal activity in the ipsilateral vestibular nucleus following unilateral labyrinthectomy in the alert guinea pig.

1. Neuronal activity was investigated in the left superior vestibular nucleus (SVN), lateral vestibular nucleus (LVN), and rostral part of the medial vestibular nucleus (MVN) in the alert guinea pig after a unilateral (left) labyrinthectomy was performed. Vestibular neurons were recorded either immediately (just-postoperative group, n = 6) or 1 wk after labyrinthectomy (1-wk-postoperative group, n = 6) and compared with the activity recorded in intact animals (control group, n = 6). 2. Animals were prepared for extracellular recording of single-unit activity and for eye movement recording (scleral search coil technique). To enable stimulation of the left vestibular nerve, bipolar silver ball electrodes were chronically implanted either in contact with the bony labyrinth in the control group or close to the stump of the vestibular nerve after labyrinthectomy. Complete labyrinthectomy was performed under halothane anesthesia. 3. The criterion used to select vestibular neurons for analysis was their recruitment by an electric shock on the vestibular nerve. Of the 589 recorded neurons, 424, defined as second-order vestibular neurons, were recruited at monosynaptic latencies (0.85-1.15 ms) and 165 were recruited at polysynaptic latencies. One hundred three second-order vestibular neurons were recorded in the control group, 173 in the just-postoperative group, and 148 in the 1-wk-postoperative group. 4. The activity of the electrically recruited neurons was recorded during sinusoidal horizontal head rotation in the dark (0.3 Hz, 40 degrees/s peak velocity). The behavior of the neurons was analyzed by plotting their firing rate against head velocity. The Y-intercept of the regression line was used to express spontaneous firing rate (resting discharge), and its slope was used to express the sensitivity of the neuron-to-head velocity. 5. In the absence of statistically significant difference between the characteristics of the neuronal discharge of the second-order vestibular neurons recorded in the SVN, LVN, and rostral MVN, the data were pooled. The Resting discharge of these cells amounted to 41.0 +/- 24.7 (SD) spikes/s in the control state, fell to 7.2 +/- 13.9 spikes/s just after labyrinthectomy, and completely returned to normal values 1 wk after surgery (42.5 +/- 21.6 spikes/s). Among the monosynaptically recruited neurons, the percentage of silent units was 0% in the control group, 69% in the just-postoperative group, and 0% in the 1-wk-postoperative group. 6. By contrast, the sensitivity to head velocity of the second-order vestibular neurons, which was 0.69 +/- 0.48 (SD) spikes.s-1/deg.s-1 in the control state and which fell to 0.03 +/- 0.11 spikes.s-1/deg.s-1 just after labyrinthectomy, remained low 1 wk after injury (0.21 +/- 0.26 spikes.s-1/deg.s-1). Moreover, the slight recovery of sensitivity to head rotation was due only to units behaving as type II neurons. 7. The mean resting discharge of the polysynaptically recruited neurons (pooled from the 3 explored nuclei) was 31.6 +/- 19.3 spikes/s in the control group. It decreased to 11.6 +/- 12.1 spikes/s in the just-postoperative group and recovered to 39.8 +/- 20.2 spikes/s in the 1-wk-postoperative group. No neuron was silent at rest either in the control group or in the 1-wk-postoperative group. Just after labyrinthectomy, 35% of the neurons had a null resting activity. The mean sensitivity to head velocity of these neurons was 0.55 +/- 0.42 spikes.s-1/deg.s-1 in the control group. It decreased to 0.05 +/- 0.12 spikes.s-1/deg.s-1 in the just-postoperative group and recovered to 0.22 +/- 0.17 spikes.s-1/deg.s-1 in the 1-wk-postoperative group. 8. We conclude that, at least in the guinea pig, the restoration of the spontaneous activity of the deafferented neurons is complete 1 wk after a unilateral labyrinthectomy and thus probably plays an important role in vestibular compensation...

Animals↗

The orientation of the cervical vertebral column in unrestrained awake animals. II. Movement strategies.

Previously we demonstrated a stereotyped resting posture of the head-neck arrangement in a number of vertebrates: the cervical vertebral column is oriented vertically to form one portion of the partial S-shaped configuration of the entire spine. The present investigation quantified the various strategies of head-neck movements employed by different mammalian species (human, monkeys, cats, rabbits and guinea pigs) using cineradiography. At rest, bipeds and quadrupeds hold their heads at the extreme point of flexion of the passive atlanto-occipital range of motion. In this posture, the horizontal semicircular canals are tilted upward from earth horizontal by 5 to 10 degrees and roughly parallel the plane determined by the two obliquus capitis posterior muscles. Furthermore, at this head position, the utricular maculae become oriented earth-horizontally. In quadrupedal animals, head-neck movements in the sagittal plane result from movement at the atlanto-occipital articulation (head/C1) and at the multi-articular cervico-thoracic junction (C6-Th3). Only very small flexion/extension movements occur within the body of the cervical vertebral column (C2-C5). Lowering the head from the resting position is only possible by flexion at the C6-Th3 vertebrae. Raising of gaze from the resting position is only possible by extension of the head at the atlanto-occipital articulation. By contrast, sagittal plane head movements in bipeds are largely confined to the cervico-thoracic junction. This is related to a significantly reduced range of motion of the atlanto-occipital articulation. In monkeys and humans, it range of motion is about 13 and 8-11 degrees, respectively, compared to 105 degrees in rabbits. Our cineradiographic data demonstrated different strategies for head movements in the sagittal plane between quadrupeds and bipeds. At one end of the spectrum, in the case of rabbits, there was no systematic relationship between head and neck orientation. Rabbits stabilized head posture by using the head-neck structure in a parallelogram fashion, which resulted in head posture being largely independent of cervical vertebral column orientation. In monkeys and humans, however, orientation of the head depended almost entirely on the orientation of the cervical vertebral column. In such case, head movements in the sagittal plane almost exclusively relied on the positioning of the cervico-thoracic junction. These different strategies again correlate with the different ranges of motion of the atlanto-occipital articulation. We suggest that vertebrates use mechanical constraints and preferred planes of action for head-neck movement control to simplify sensory-motor transformations subserving motor control and plasticity and to minimize neuronal operations.

Animals↗

Functional anatomy of the head-neck movement system of quadrupedal and bipedal mammals.

This biomechanical investigation quantified the range of motion of the different articulations of the head-neck ensemble in man, monkeys, cats, rabbits and guinea pigs. Radiography and dissections were used to establish the degrees of freedom of the system. The erect posture and rigidity of the cervical spine in mammalian vertebrates are possible because the degrees of freedom of the movements of the cervical and upper thoracic vertebrae in passive ranges of motion are asymmetric, and thus significantly restricted, when judged from the resting position. The total range of motion at the atlanto-occipital articulation varies between species. It is approximately 90 degrees-105 degrees in the quadrupedal mammals tested, and only 11 degrees or 13 degrees, respectively, in humans and monkeys. When at rest, bipeds and quadrupeds hold the atlanto-occipital articulation and the upper cervical joints (C1/C2, C2/C3) in a flexed attitude. The total range of motion at the cervicothoracic junction (C6-T2) is approximately 6 degrees-80 degrees in all vertebrates investigated (quadrupeds and bipeds). At rest, the vertebral articulations that form the cervicothoracic junction are held in their extreme extended positions in quadrupeds and monkeys. In man, the vertebrae of the lower cervical spine are kept at a midposition between maximal flexion and maximal extension. This latter observation may be related to the permanent bipedalism of humans. Collectively, our data indicate that biomechanical constraints such as bone structures (e.g. specifically shaped articular processes) and ligaments may maintain the intrinsic configuration and self-supporting structure of the cervical spine. Furthermore, the specialised structures in the cervical joints allow movements more or less in particular planes of space, and thus biomechanical constraints limit the number of possible solutions as to how an animal can perform a given orientating head movement. Although we have not entirely clarified the functional implications for head movement control of the different sagittal-plane ranges of motion in vertebrates, we hypothesise that different mechanical requirements relating to the influence of gravity have caused the observed differences between the investigated bipedal and quadrupedal mammals.

Animals↗

Distribution of glutamatergic receptors and GAD mRNA-containing neurons in the vestibular nuclei of normal and hemilabyrinthectomized rats.

Vestibular compensation is an attractive model for investigations of cellular mechanisms underlying post-lesional plasticity in the adult central nervous system. Immediately after hemilabyrinthectomy, the spontaneous activity in the deafferented second-order vestibular neurons falls to zero, resulting in a strong asymmetry between the resting discharge of the vestibular complexes on the lesioned and intact sides. This asymmetry most probably causes the static and dynamic vestibular deficits observed in the acute stage. After approximately 50 h, the deafferented vestibular neurons recover a quasi-normal resting activity which is thought to be the key of the compensation of the static vestibular syndromes. However, the molecular mechanisms underlying this recovery are unknown. In this study, we investigate possible changes in the distribution of glutamatergic N-methyl-D-aspartate (NMDA) and glutamate metabotropic receptors and of glutamate decarboxylase 67k (GAD 67k) mRNAs in the deafferented vestibular neurons induced by the labyrinthine lesion. Specific radioactive oligonucleotides were used to probe sections of rat vestibular nuclei according to in situ hybridization methods. Animals were killed at different times (5 h, 3 days and 3 weeks) following the lesion. Signal was detected by means of film or emulsion autoradiography. In the normal animals, several brainstem regions including the medial, lateral, inferior and superior vestibular nuclei were densely labelled by the antisense oligonucleotide NMDAR1 probe. However, the vestibular nuclei were not labelled by the glutamate metabotropic oligonucleotide antisense probe (mGluR 1). The GAD 67k antisense oligonucleotide probe labelled numerous small- to medium-sized central vestibular neurons but not the larger cell bodies in the lateral vestibular nucleus. This agrees with previous studies. In the hemilabyrinthectomized rats, no asymmetry could be detected, at either the autoradiographic or cellular levels, between the two medial vestibular nuclei whatever the probe used and whatever the delay following the lesion. However, for the NMDAR1 probe, the mean density of silver grains in both the deafferented and intact medial vestibular neurons was 20% lower 5 h after the lesion. Three days and 3 weeks later, the intensity of labelling over all cells was the same as in the control group. Further studies are necessary to confirm the relatively weak modification of the NMDAR1 mRNAs expression and to exclude a change of GAD 65 and of other NMDA subunit mRNAs during the vestibular compensation process.

Animals↗

Medial vestibular nucleus in the guinea-pig: histaminergic receptors. II. An in vivo study.

In a companion paper (Serafin et al. 1992) we have demonstrated in vitro that histamine depolarizes three previously described medial vestibular nucleus neuron (MVNn) types (Serafin et al. 1991a, b). It has also been shown that this effect was exclusively mediated through postsynaptic H2 receptors. All the same, the eventual contribution of presynaptic H3 receptors to the physiological response of the MVNn to histamine remained an open question since, during the slicing procedure, any histaminergic axons projecting to the vestibular nuclei would have been interrupted. This rendered our study of H3-mediated effects of histamine difficult. Hence, in the present in vivo study our aim was three-fold: (1) to investigate the presence of H3 receptors at the vestibular nuclei level; (2) to evaluate the functional importance of MVNn H2 receptors; and (3) to explore whether H3 ligands, when injected intraperitoneally (i.p.), could modulate dynamic vestibular functions. In order to address the first two questions, we investigated postural changes induced by perfusion of the guinea-pig's vestibular nuclear complex with specific ligands of the H2 and H3 receptors. Our data extend the conclusions of our in vitro study and suggest that lateral vestibular nuclei neurons and the MVNn are endowed with both H2 and H3 receptors. Our results indicate furthermore that histamine can modulate, quite effectively, static vestibular reflexes. Finally, the present study demonstrates that i.p. injection of thioperamide, an H3 antagonist, induces a significant decrease in the horizontal vestibular-ocular reflex gain and, by contrast to most of the clinically used antihistaminics, has no detrimental effect on the alertness level. Our results may thus lead to clinical testing and use of H3 antagonists as antivertigo or anti motion-sickness drugs.

Animals↗

Saccadic eye movements and the horizontal vestibulo-ocular and vestibulo-collic reflexes in the intact guinea-pig.

The guinea-pig is an attractive model for investigating gaze stabilization because it is suitable for in vitro and in vivo studies. However, few data are available on its oculomotor performance. We therefore investigated spontaneous eye movements, horizontal vestibulo-ocular (HVOR) and vestibulo-collic reflexes (HVCR) in the alert head-fixed guinea-pig using the magnetic search coil method. First the characteristics of the spontaneous saccades in the light were analysed. They occurred with a mean frequency of 4.6/min and with a mean amplitude and duration of 7.41 +/- 3.57 deg and 30.9 +/- 9.5 ms, respectively (n = 340). Saccadic duration and velocity were linearly related to the amplitude of the eye movement. The HVOR was studied in response to sinusoidal rotations (0.01 Hz to 2 Hz, peak head velocity of 40 deg/s) in the dark. Vestibular responses were linear at 0.5 and 0.05 Hz for peak head velocities between 40 and 80 deg/s. As in other species, the gain increased and the phase lead decreased with increasing frequencies. The number of fast phases per second increased with peak head velocity and with increasing frequencies from 0.01 to 0.5 Hz, with a plateau between 0.2 and 0.5 Hz. The HVOR time constant, when measured in response to velocity steps, was 7.0 +/- 1.5 s and the latency of the vestibular responses averaged 21 +/- 4 ms. Finally, the HVCR was assessed in unrestrained guinea-pigs subjected to horizontal sinusoidal rotation in the frequency range of 0.05-2 Hz. Exploratory behaviour was prevalent and there were few head stabilization episodes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The horizontal vestibulo-ocular reflex in the hemilabyrinthectomized guinea-pig.

The horizontal vestibulo-ocular reflex (HVOR) in the alert guinea-pig elicited by sinusoidal rotations and by velocity steps was studied with scleral search coil measurement between 3 and 7 days (short term) and between 35 and 160 days (long term) after hemilabyrinthectomy. Animals of the short-term group were always tested after spontaneous nystagmus in darkness had disappeared. The HVOR gain in response to sinusoidal rotations (peak angular velocity: 40 deg/s) in the short-term group was bilaterally depressed compared to normal animals. The HVOR phase showed a shift towards larger phase leads over the whole frequency range tested (from 0.05 to 3 Hz). In addition, both the mean number of fast phases per half-cycle of sinusoidal rotation and the mean amplitude were reduced. HVOR responses to velocity steps at a constant acceleration of 300 deg/s2 up to final velocity (0 to 100 deg/s) and of 1000 deg/s2 up to final velocity (0 to 300 deg/s) were depressed bilaterally and asymmetrically such that the gain for rotation towards the intact side greatly exceeded that obtained for rotation towards the lesioned side. Finally, the latency of the vestibular responses was increased and the time constant reduced for both sides of rotation. The HVOR gain values for sinusoidal rotations in the long-term group were lower than normal but higher than in the short-term group: they were asymmetric as a result of a greater compensation for rotation towards the intact side. Neither the phase lead nor the HVOR latency and time constant recovered values close to normal. Finally, the mean number of fast phases per half-cycle remained depressed although the mean amplitude recovered. These results demonstrate that in the guinea-pig, the dynamic deficits show a certain degree of recovery after unilateral labyrinthectomy. However, compared to the compensation of the static deficits previously quantified, the rate of recovery is much lower. This suggests that different processes may be involved in the compensation of the static and dynamic deficits.

Animals↗

Medial vestibular nucleus in the guinea-pig: apamin-induced rhythmic burst firing--an in vitro and in vivo study.

In a previous in vitro study, we have shown that guinea-pig medial vestibular nucleus neurons (MVNn) can be grouped into two main cell types based on their intrinsic membrane properties. Subsequent in vivo and in vitro studies demonstrated that these neurons are endowed with N-methyl-D-aspartate (NMDA) receptors and that NMDA induces rhythmic bursts in B MVNn. We now report the occurrence of rhythmic bursts in B MVNn (and in the subclass of B+LTS MVNn) which are induced by long-lasting perfusion of either apamin, a selective blocker of one type of Ca(2+)-dependent K+ conductance (SK channels), or by a high Mg2+/low Ca2+ artificial cerebrospinal fluid. Apamin-induced bursts were studied in vitro in brainstem slices, and in vivo in the alert unrestrained guinea-pig. In vitro, intracellular recordings demonstrated that the frequency of the bursts was voltage dependent. These bursts were insensitive to D-2-amino-5-phosphopentanoic acid but could be abolished by tetrodotoxin or blocked by the bath application of 20-50 microM of ouabain, a blocker of the sodium pump. In the in vivo preparation, unilateral infusion of apamin into the vestibular nuclei induced oscillatory head and eye movements. Our data show that the blockade of a Ca(2+)-activated K+ conductance may switch, in vitro and probably in vivo, the B MVn firing pattern from a regular to a bursting firing pattern.

2-Amino-5-phosphonovalerate↗

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.

Afferent Pathways↗

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.

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↗

Medial vestibular nucleus in the guinea-pig. I. Intrinsic membrane properties in brainstem slices.

Intracellular recordings were obtained from medial vestibular nuclei neurones (MVNn) in guinea-pig brainstem slices. Two main distinct neuronal classes were encountered. Type A MVNn (32.3%) were characterized by a broad action potential followed by a deep single afterhyperpolarization, a transient A-like rectification, and a single range of firing in response to current injection. Type B MVNn (47.1%), in contrast, were distinguished by the presence of a thin action potential followed first by a fast and then by a delayed and slower afterhyperpolarization. In addition, they displayed a secondary range of firing in their response to current injection. A majority of B MVNn also had either sub-threshold plateau potentials or low threshold spike bursts or a combination thereof. A third, non-homogeneous class of cells, could not be fitted into either one of the two main classes (20.6%, type C MVNn).

Action Potentials↗

Medial vestibular nucleus in the guinea-pig. II. Ionic basis of the intrinsic membrane properties in brainstem slices.

In the preceding paper, medial vestibular nuclei neurones (MVNn) were shown to belong to two main classes, A MVNn and B MVNn, depending on their membrane properties in brainstem slices. In the following study we attempted to confirm this segregation by studying some of the ionic conductances that these cells are endowed with. Type A MVNn demonstrated small high threshold calcium spikes that could be potentiated by barium, a 4-AP resistant A-like conductance and a calcium-dependent afterhyperpolarization. Type B MVNn, in contrast, had large high threshold calcium spikes and prolonged calcium-dependent plateau potentials. In addition, they had a calcium-dependent afterhyperpolarization as well as a subthreshold persistent sodium conductance. A subpopulation of B MVNn had also low threshold calcium spikes that gave them bursting properties. These data confirm the segregation of MVN neurones into two main classes and will be discussed with respect to the firing characteristics of vestibular neurones in vivo.

4-Aminopyridine↗

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.

Afferent Pathways↗