Nicolas Vibert

Central vestibular networks in the guinea-pig: functional characterization in the isolated whole brain in vitro

The isolated, in vitro whole brain of guinea-pig was used to assess some of the main physiological and pharmacological properties of the vestibulo-ocular pathways in this species. Extracellular and intracellular recordings were obtained from the vestibular, abducens and oculomotor nuclei, as well as from the abducens and oculomotor nerves, while inputs from the vestibular afferents, the visual pathways and the spinal cord were activated. The three main types of medial vestibular nucleus neurons (A, B and B+LTS), previously described on slices, were also identified in the isolated brain. They had similar membrane properties in both preparations. Eighty-five per cent of cells recorded in the vestibular nucleus responded with monosynaptic, excitatory postsynaptic potentials (latency 1.05-1.9 ms) to stimulation of the ipsilateral vestibular nerve, and were thus identified as second-order vestibular neurons. In addition, stimulation of the contralateral vestibular afferents revealed in most cases a disynaptic or trisynaptic, commissural inhibition. Second-order vestibular neurons displayed in the isolated brain a high degree of variability of their spontaneous activity, as in alert guinea-pigs. Type A neurons always exhibited a regular firing, while type B and B+LTS cells could have very irregular patterns of spontaneous discharge. Thus, type A and type B neurons might correspond, respectively, to the tonic and phasic vestibular neurons described in vivo. The regularity of spontaneous discharge was positively correlated with the amplitude of spike after hyperpolarization, and there was a trend for irregular neurons to be excited from ipsilateral vestibular afferents at shorter latencies than regular units. Synaptic activation could trigger subthreshold plateau potentials and low-threshold spikes in some of the second-order vestibular neurons. As a second step, the pharmacology of the synaptic transmission between primary vestibular afferents and second-order neurons was assessed using specific antagonists of the glutamatergic receptors. Both the synaptic field potentials and excitatory postsynaptic potentials elicited in the medial vestibular nucleus by single shock stimulation of the ipsilateral vestibular nerve were largely or, sometimes, totally blocked by 6-cyano-7-nitroquinoxaline-2,3-dione, indicating a dominating role of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated glutamatergic transmission. The remaining component of the responses was completely or partially suppressed by DL-2-amino-5-phosphonovaleric acid in 35% of the cases, suggesting a concomitant, moderate involvement of N-methyl-D-asparate receptors. In addition, a synaptic response resistant to both antagonists, but sensitive to a zero Ca2+/high Mg(2+)-containing solution, was often observed. Finally, recordings from abducens and oculomotor complexes confirmed the existence in the guinea-pig of strong bilateral, disynaptic excitatory and inhibitory inputs from vestibular afferents to motoneurons of extraocular muscles, which contribute to generation of the vestibulo-ocular reflex. The functional integrity of vestibular-related pathways in the isolated brain was additionally checked by stimulation of the spinal cord and optic tract. Stimulation of the spinal cord evoked, in addition to antidromic responses in the vestibular nucleus, short-latency synaptic responses in both the vestibular nucleus and abducens motoneurons, suggesting possible recruitment of spinal afferents. Activation of visual pathways at the level of the optic chiasm often induced long latency responses in the various structures under study. These results demonstrate that the in vitro isolated brain can be readily used for detailed, functional studies of the neuronal networks underlying gaze and posture control.

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. (Otolaryngol Head Neck Surg 1998;119:34–42.)

Readers’ use of source information in text comprehension

In two experiments, we examined the role of discrepancy on readers’ text processing of and memory for the sources of brief news reports. Each story included two assertions that were attributed to different sources. We manipulated whether the second assertion was either discrepant or consistent with the first assertion. On the basis of the discrepancy-induced source comprehension (D-ISC) assumption, we predicted that discrepant stories would promote deeper processing and better memory for the sources conveying the messages, as compared to consistent stories. As predicted, readers mentioned more sources in summaries of discrepant stories, recalled more sources, made more fixations, and displayed longer gaze times in source areas when reading discrepant than when reading consistent stories. In Experiment 2, we found enhanced memory for source–content links for discrepant stories even when intersentential connectors were absent, and regardless of the reading goals. Discussion was focused on discrepancies as one mechanism by which readers are prompted to encode source–content links more deeply, as a method of integrating disparate pieces of information into a coherent mental representation of a text.

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 scierai 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.

Vestibular evoked myogenic potentials in patients suffering from an unilateral acoustic neuroma: a study of 170 patients

OBJECTIVE To determine the value of investigating the vestibular evoked myogenic potentials (VEMPs) induced by clicks and 500 Hz short tone burst (STB) for the diagnosis of acoustic neuromas. METHODS We studied the average responses to 100dB clicks and 500 Hz STB in the ipsilateral sternomastoid muscle. Ninety-five healthy subjects and 170 patients suffering from a unilateral acoustic neuroma were included in that study. Caloric and audiometric tests results were also analyzed. RESULTS Thirty-six/170 patients (21.2%) exhibited normal responses to clicks and to STB whereas 134/170 (78.8%) gave abnormally low or no responses. 78/170 (45.9%) showed no responses to both clicks and STB. In 56/170 patients (32.9%), VEMPs induced by high level clicks and STB were discordant: STB VEMPs were either normal (n=32) or low (n=24) in patients with an abnormal response to clicks (no response n=40 or low response n=16). In contrast, STB-induced VEMPs were always normal in cases of normal responses to clicks. No strong, systematic correlation could be found between saccular nerve dysfunction and either the degree of 4-8 kHz hearing loss or the extent of horizontal canalar impairment. CONCLUSIONS These data indicate that high level clicks and STB provide complementary information about the functionality of the saccular nerve. Clicks are useful to detect a minor saccular nerve dysfunction. In cases in which there is no response to clicks, STB gives valuable information about a potential residual function of the saccular nerve.

Vestibular compensation modifies the sensitivity of vestibular neurones to inhibitory amino acids.

The progressive disappearance of the postural and oculomotor syndrome triggered by unilateral labyrinthectomy (vestibular compensation) is a model of plasticity in the adult central nervous system. This recovery may involve modifications of the pharmacological profile of central vestibular neurones, in particular their sensitivity to inhibitory amino acids. We therefore compared the sensitivity of medial vestibular nucleus neurones to glycine and muscimol in slices taken either from control animals, or from guinea-pigs labyrinthectomized 3 days before. We demonstrate that the loss of excitatory inputs experienced by the ipsilesional vestibular neurones induces a decrease in their sensitivity to inhibitory amino acids. These pharmacological changes should facilitate the recovery of a normal balance between the average resting discharge of neurones in both vestibular nuclei.

Differential Intrinsic Response Dynamics Determine Synaptic Signal Processing in Frog Vestibular Neurons

Central vestibular neurons process head movement-related sensory signals over a wide dynamic range. In the isolated frog whole brain, second-order vestibular neurons were identified by monosynaptic responses after electrical stimulation of individual semicircular canal nerve branches. Neurons were classified as tonic or phasic vestibular neurons based on their different discharge patterns in response to positive current steps. With increasing frequency of sinusoidally modulated current injections, up to 100 Hz, there was a concomitant decrease in the impedance of tonic vestibular neurons. Subthreshold responses as well as spike discharge showed classical low-pass filter-like characteristics with corner frequencies ranging from 5 to 20 Hz. In contrast, the impedance of phasic vestibular neurons was relatively constant over a wider range of frequencies or showed a resonance at ∼40 Hz. Above spike threshold, single spikes of phasic neurons were synchronized with the sinusoidal stimulation between ∼20 and 50 Hz, thus showing characteristic bandpass filter-like properties. Both the subthreshold resonance and bandpass filter-like discharge pattern depend on the activation of an ID potassium conductance. External current or synaptic stimulation that produced impedance increases (i.e., depolarization in tonic or hyperpolarization in phasic neurons) had opposite and complementary effects on the responses of the two types of neurons. Thus, membrane depolarization by current steps or repetitive synaptic excitation amplified synaptic inputs in tonic vestibular neurons and reduced them in phasic neurons. These differential, opposite membrane response properties render the two neuronal types particularly suitable for either integration (tonic neurons) or signal detection (phasic neurons), respectively, and dampens variations of the resting membrane potential in the latter.

Medial vestibular nucleus in the guinea-pig: histaminergic receptors

SummaryAntihistaminergic 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 neurones (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).

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. However, when it occurred, the HVCR gain and phase were relatively flat over a frequency range from 0.1 to 2 Hz, reaching values close to 0.9 and 12 deg, respectively. In summary, the saccadic eye movements, the HVOR and the HVCR in the guinea-pig appear to be sufficiently similar to those of other vertebrates, including humans, to allow this species to be used as a model for studies of new pharmacological agents for vestibular disorders and post-lesional plasticity.

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.