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N Vibert

Publications and source records attributed to N Vibert.

28 records · Page 2Linked to original sources

Dopaminergic agonists have both presynaptic and postsynaptic effects on the guinea-pig's medial vestibular nucleus neurons.

A number of studies have indicated a possible interaction between dopamine and the vestibular system. Using intracellular recordings in brainstem slices, we have tested the effects of dopamine and other dopaminergic compounds on guinea-pig medial vestibular nucleus (MVN) neurons. In normal medium, MVN neurons were depolarized by dopamine as well as by (-)quinpirole and piribedil, which are selective D2 dopaminergic agonists. The dependence of this effect on the presence of D2 receptors was confirmed by using (-)sulpiride, a D2 antagonist which blocked the depolarizing effect of dopamine. Dopaminergic D1 receptors were apparently not involved in this effect since a selective D1 agonist, SKF-38393, had no effect on MVN neurons and the D1 antagonist (+)SCH-23390 could not block the effect of dopamine. These depolarizing responses to dopamine must be due to a presynaptic action on terminals that normally release GABA spontaneously on MVN neurons, and tonically maintain them in a state of hyperpolarization. Indeed, such a spontaneous release was demonstrated to occur in the slice since application of bicuculline, a GABAA antagonist, depolarized MVN neurons in normal saline, but not in a high Mg2+/low Ca2+ solution known to block synaptic transmission. When dopamine was applied in conditions in which no GABAA-dependent transmission could occur (either in the presence of bicuculline or in a high Mg2+/low Ca2+ solution) only a hyperpolarizing, most probably postsynaptic, effect occurred. These results indicate that dopamine might exert in vivo a significant modulatory action on the vestibular system, either by a direct action on the vestibular neurons or by modulation of GABAergic transmission.

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Effects of baclofen on medial vestibular nucleus neurones in guinea-pig brainstem slices.

Using intracellular recordings of medial vestibular nucleus neurones (MVNn) in guinea-pig brainstem slices, the effects of baclofen, a specific agonist of the metabotropic GABAB receptors, were tested on the three main types of MVNn (A, B and B + LTS MVNn) that were previously identified in this nucleus. Regardless of their type, almost all MVNn were hyperpolarized and inhibited by baclofen. These hyperpolarizing effects persisted following either the addition of tetrodotoxin (TTX) in the perfusion medium, or in the presence of a high Mg2+/low Ca2+ solution known to block synaptic transmission. These results demonstrate that all types of MVNn are endowed with postsynaptic GABAB receptors.

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Direct and indirect effects of muscimol on medial vestibular nucleus neurones in guinea-pig brainstem slices.

Inhibitory amino acids are considered as major transmitters in the vestibular system. Using intracellular recordings in slices, we applied gamma-aminobutyric acid (GABA) and muscimol (a specific agonist of the GABAA receptor) to the two main types of medial vestibular nucleus neurones (A and B MVNn). In either a high Mg2+/low Ca2+ solution, or a solution containing tetrodotoxin, all MVNn were hyperpolarized by GABA and muscimol. This indicates that both types of MVNn are endowed with postsynaptic, hyperpolarising GABAA receptors. In a normal medium, about half of A and B MVNn were, in contrast, depolarised by GABA and muscimol, whereas the remaining cells were hyperpolarised. These results could be due to a modulation by GABA and muscimol of a tonic GABA release in the slice. Such a release was, indeed, suggested by results showing the depolarising effect of either tetrodotoxin (TTX) or bicuculline, when applied alone. The cells that were depolarised by GABA or muscimol in control conditions were always hyperpolarised in the presence of TTX. Our data therefore suggest that GABA acting at GABAA receptors in the medial vestibular nucleus can play a role either through a postsynaptic hyperpolarising action or indirectly by inhibiting a tonic GABA release, probably resulting from the spontaneous activity of local inhibitory interneurones. A GABAergic regulation of these interneurones could be important in processes of vestibular habituation and/or adaptation.

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Medial vestibular nucleus in the guinea-pig: histaminergic receptors. I. An in vitro study.

Antihistaminergic drugs are currently used for the symptomatic treatment of vestibular-related syndromes such as vertigo and motion sickness. We therefore investigated whether histamine could modulate the firing of medial vestibular nuclei neurons (MVNn). Recently, we have demonstrated that different cell types are present among MVNn in guinea-pig brainstem slices. Bath-application of histamine at 10(-4) or 10(-5) M induced a small membrane depolarization accompanied by a slight decrease in membrane resistance and a reversible increase in spontaneous firing in all MVN cell types. These effects were presumably postsynaptic as they persisted in a low-calcium/high-magnesium solution. Using a variety of agonists and antagonists of histamine receptors (H1, H2 and H3), we conclude that these effects are mediated by H2 receptors. The companion paper is concerned with an in vivo study of the histaminergic modulation of the vestibular function (Yabe et al., in press).

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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.

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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)

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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.

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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.

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NMDA receptors contribute to the resting discharge of vestibular neurons in the normal and hemilabyrinthectomized guinea pig.

Excitatory amino acids (EAA) like L-Glutamate or L-Aspartate have been suggested to be the neurotransmitters at the synapses between primary vestibular afferents and second-order vestibular neurons. In the first part of our work, we have tested the possibility that EAA receptors are implicated in the control of posture by vestibular nuclei. Normal guinea pigs were implanted with minipumps delivering EAA antagonists in the vestibular nuclei. Their resting posture was monitored during the perfusion by using an X-ray photographic method. Chronic infusion of D-L-2-amino-5-phosphonovaleric acid (APV), a specific antagonist of NMDA receptors, in the vestibular nuclei induced a postural and oculomotor syndrome similar to the one observed following acute vestibular deafferentation. Administration of 6-cyano-7-nitro-quinoxaline-2-3-dione (CNQX), a specific antagonist of kainate and quisqualate receptors, failed to induce any postural syndrome or eye deviation. These results suggest that, under physiological conditions, N-methyl-D-aspartate (NMDA) receptors, contrary to kainate and quisqualate receptors, are essential for the maintenance of a symmetric posture and of a normal eye position at rest. Previous electrophysiological studies have demonstrated that following unilateral labyrinthectomy the recovery of a resting discharge in the deafferented vestibular nuclei plays a key role in the compensation of postural disorders. In the second part of this study, we have tested whether NMDA receptors could be implicated in this postural recovery. APV mini-pumps were implanted in hemilabyrinthectomized guinea pigs after complete compensation. A postural decompensation was induced, which occurred after delivery of the same amount of APV which provoked a vestibular syndrome in intact guinea pigs.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗