C. de Waele

Medial vestibular nucleus in the guinea-pig

SummaryIntracellular 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 subthreshold 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).

A radiological analysis of the postural syndromes following hemilabyrinthectomy and selective canal and otolith lesions in the guinea pig.

SummaryX-ray photography was employed to analyse the postural syndromes following unilateral global and selective lesions of the vestibular apparatus in guinea pigs. Following hemilabyrinthectomy, head rotation in the horizontal plane resulted mainly from rotation of the cervical vertebrae whereas lateral head tilt was due to the rotation of thoracic vertebrae about the longitudinal axis. These results support our previous conclusion that because of both resting posture and intrinsic biomechanical constraints, the number of degrees of freedom of the cervical column is reduced and the cervical vertebrae are functionally specialized. Selective lesions of the vestibular apparatus have aided in determining the origin of the different components of the hemilabyrinthectomy syndrome: rotation of thoracic vertebrae was caused by unilateral lesion of the otolithic system whereas rotation of the head in the horizontal plane resulted from unilateral lesion of the horizontal semicircular canal system. We conclude that the functional segmentation of the cervical column corresponds to a differential distribution of vestibular afferents.

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

SummaryExcitatory 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 minipumps 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. This result favors the hypothesis that denervation supersensitivity resulting from an increase in either the number and/or the sensitivity of NMDA receptors could be a factor in the recovery of the static syndrome following hemilabyrinthectomy.

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.

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.

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 Ca2–-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 μM 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 Ca2–-activated K– conductance may switch, in vitro and probably in vivo, the B MVNn firing pattern from a regular to a bursting firing pattern.

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.

The Orientation of the Cervical Vertebral Column in Unrestrained Awake Animals (Part 1 of 2)

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 partia

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.