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PubMed2005

Afferent pathways to the region of the vestibular nuclei that participates in cardiovascular and respiratory control.

Prior experiments have shown that a region of the medial and inferior vestibular nuclei contributes to cardiovascular and respiratory regulation. In addition to labyrinthine inputs, the majority of neurons in this region of the vestibular nuclei receive signals from the skin, muscle, and viscera, although the pathways conveying these nonlabyrinthine inputs to the vestibular nucleus neurons are unknown. To gain further insight into the afferent pathways to this functionally distinct subdivision of the vestibular complex, we combined monosynaptic mapping with viral transneuronal tracing in the ferret. First order afferent projections were defined by retrograde transport of the beta-subunit of cholera toxin (CTbeta), and the extended polysynaptic circuitry was defined in the same animals by injection of a recombinant of pseudorabies virus Bartha (PRV) into the contralateral vestibular nuclei. Neurons containing CTbeta or infected by retrograde transneuronal transport and replication of PRV were distributed throughout the spinal cord, but were 10 times more prevalent in the cervical cord than the lumbar cord. The labeled spinal neurons were most commonly observed in Rexed's laminae IV-VI and the dorsal portions of laminae VII-VIII. Both the CTbeta and PRV injections also resulted in labeling of neurons in all four vestibular nuclei, the prepositus hypoglossi, the reticular formation, the inferior olivary nucleus, the medullary raphe nuclei, the spinal and principal trigeminal nuclei, the facial nucleus, and the lateral reticular nucleus. Following survival times >/=3 days, PRV-infected neurons were additionally present in nucleus solitarius and the gracile and cuneate nuclei. These data show that an anatomical substrate is present for somatosensory and visceral inputs to influence the activity of cells in the autonomic region of the vestibular nuclei and suggest that these signals are primarily transmitted through brainstem relay neurons.

Afferent Pathways↗
PubMedDate not supplied

Second-order neural responses after contralateral vestibular nerve sectioning.

The characteristics of the response to an 8 degrees/sec2 acceleration of 41 neurons in the medial vestibular nucleus of the cat following vestibular nerve sectioning were compared with those of 73 control neurons at the same site. In 14 of the vestibular nerve-sectioned animals the same neuron was recorded before and after sectioning. No difference was found between the resting discharge rates, maximal response rates, and rates of adaptation of the two groups. Following contralateral vestibular nerve sectioning Type II neurons were still plentiful, suggesting many receive ipsilateral labyrinthine innervation.

Action Potentials↗
PubMed1996

A simple and reliable technique to combine oligonucleotide probe in situ hybridization with neuronal tract tracing in vertebrate embryos.

We describe a simple and reliable combination of in situ hybridization with neuronal tracing. The technique uses recent advances in the field of neuronal tract tracing including fast diffusing, low molecular weight dextran amines and fade resistant fluorescent dyes, and combines them with in situ hybridization using a sensitive oligonucleotide probe. Using this technique we have investigated the mRNA encoding the trkB receptor for brain-derived neurotrophic factor in identified facial and vestibular afferent and efferent neurons. We found very low levels of trkB mRNA in facial efferent neurons, whereas in the vestibular afferent neurons, clear labeling for the trkB mRNA could be seen. This technique can be applied to the developing embryo to study topology of a variety of cellular markers with reference to neuronal population or fibers identified by their origin or target.

Animals↗
PubMed2004

Effect of a glutamate blocker, ipenoxazone hydrochloride on the hypoxia-induced firing in the medial vestibular nucleus.

To elucidate the effectiveness of the drug in the treatment of vertebrobasilar insufficiency (VBI), we performed an electrophysiological study to examine the effects of ipenoxazone hydrochloride, a glutamate blocker, on hypoxia-induced firing in the medial vestibular nucleus (MVN) neuron, using alpha-chloralose-anesthetized cats. The single neuronal activity of the MVN was recorded extracellularly with a glass-insulated silver wire microelectrode attached along a seven-barrel micropipette. The firing rate of MVN neurons showed a transient increase [hypoxic depolarization (HD)] during 5% O(2) inhalation, followed by a gradual decrease and disappearance. HD and the time to disappearance of firing induced by hypoxia were inhibited by iontophoretic application of ipenoxazone hydrochloride. These results suggest that ipenoxazone hydrochloride protects against hypoxic neuronal dysfunction, and may be an effective drug for vertigo caused by VBI.

Animals↗
PubMed1995

Metabotropic glutamate receptors in the guinea-pig medial vestibular nucleus in vitro.

Despite the accumulation of a large body of evidence on the function of the kainate/alpha-amino-3-5-methyl-4-iso-xazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) excitatory amino acid (EAA) receptor subtypes within the vestibular nucleus, little is known of the metabotropic receptor subtype. The aim of the present study was to examine the response of guinea-pig medial vestibular nucleus (MVN) neurons in brain stem slices to the selective metabotropic receptor agonist, 1S,3R-amino-cyclopentyl-1,3-dicarboxylate (ACPD). Sixty percent (12/20) of MVN neurones responded to 1S,3R-ACPD at a concentration of 10(-6) M, compared with 40% (8/20) and 35% (7/20) of neurones at concentrations of 10(-8) and 10(-10) M. Both increases and decreases in firing rate were observed in different neurones: in general, the magnitude of the responses was large and the duration of the responses was long. Recordings from a slice which contained only the MVN confirmed that these responses were produced by the action of the metabotropic agonist within the MVN itself. These results demonstrate that many MVN neurones have functional metabotropic receptors.

Animals↗
PubMed2001

Damage to the vestibular inner ear causes long-term changes in neuronal nitric oxide synthase expression in the rat hippocampus.

The vestibular inner ear detects head acceleration and initiates compensatory eye movement and postural reflexes that help keep the visual image of the world stable on the retina, and maintain balance, during unexpected head movement. The most primitive vestibular systems are estimated to have evolved more than 500 million years ago and in mammalian and submammalian species the vestibular reflexes are mediated by basic brainstem pathways (see Wilson and Melvill Jones, 1979 for review). Although the contributions of the vestibular system to higher cognitive function have generally received less attention than its reflexive roles, vestibular sensory information is transmitted to higher centres in the brain and humans with vestibular damage are known to experience debilitating perceptual illusions (see Curthoys and Halmagyi, 1995; Berthoz, 1996 for reviews). Increasing behavioural and neurophysiological evidence suggests that the hippocampus uses information from the vestibular inner ear in order to build up maps of space that can be used in the development of spatial memory during learning tasks (McNaughton et al., 1991; Chapuis et al., 1992; Wiener and Berthoz, 1993; O'Mara et al., 1994; Wiener et al., 1995; Gavrilov et al., 1995; Stackman and Taube, 1996; Vitte et al., 1996; Taube et al., 1996; Save et al., 1998; Peruch et al., 1999; Cuthbert et al., 2000; Russell et al., 2000). However, to date, there has been no indication of the long-term neurochemical effects of the loss of vestibular input on hippocampal function. Since nitric oxide has been implicated in the mechanisms of hippocampal synaptic plasticity associated with the development of short-term memory (e.g. Schuman and Madison, 1991; Schuman et al., 1994; Arancio et al., 1996; Wu et al., 1997; Lu et al., 1999), we examined whether changes occur in the activity and expression of the enzymes responsible for nitric oxide production (nitric oxide synthases) in subregions of the rat hippocampus at different times following unilateral peripheral vestibular lesions, using western blotting and radioenzymatic assays. We found a decreased expression of neuronal nitric oxide synthase in the ipsilateral dentate gyrus at 2 weeks following the vestibular damage and not before, that may be related to the long-term effects of the loss of vestibular input on hippocampal function. These results support the hypothesis that head movement and position information derived from the vestibular inner ear may be important for the normal function of the hippocampus.

Afferent Pathways↗
PubMed1981

Vestibular nerve activity in the alert monkey during vestibular and optokinetic nystagmus.

Activity of vestibular nerve fibers and eye movements were recorded in the alert monkey during natural stimulation. The animal was rotated about a vertical axis in the dark with velocity trapezoids (vestibular), or a striped cylinder was rotated around the stationary monkey ()optokinetic), or these stimuli were combined. After velocity steps in the dark, neuronal activity declined with a dominant time constant of 5-6 s. The time constant of nystagmus recorded simultaneously was always longer, on average 23 s. Vestibular nerve activity was not influenced by optokinetic patterns or additional visual stimuli during combined visual-vestibular stimulation. Thus, in contrast to vestibular nuclei neurons, vestibular nerve activity in the alert monkey is only determined by head acceleration and cannot be related to the nystagmus response or visual stimuli.

Animals↗
PubMed1996

Discharge properties of brain stem neurons projecting to the flocculus in the alert cat. I. Medical vestibular nucleus.

1. The aim of this study was to characterize the signals transmitted by neurons of the medial vestibular nucleus (MVN) to the middle zone of the flocculus in alert cats. 2. Bipolar stimulating electrodes were implanted into the middle zone of each flocculus, because this zone is known to be involved in the control of horizontal eye movements. Correct implantation of the stimulating electrodes was ensured by 1) recording of Purkinje cells whose activity was related to horizontal eye movements and 2) elicitation of slow abduction of the ipsilateral eye upon electrical stimulation. 3. The rostral two-thirds of the MVN were investigated by microelectrodes during stimulation of both flocculi. Antidromically activated neurons were found only in the central part of the explored area. Forty-four units were activated from the contralateral, eight from the ipsilateral flocculus. Neurons could never be activated from both flocculi. 4. Neurons included in this study were MVN neurons that had 1) to be antidromically activated from one flocculus and 2) to modulate their firing rate during the horizontal vestibuloocular reflex (VOR) elicited by sinusoidal stimulation (0.1 Hz; 10, 20, 30 or 40 degrees). The 39 neurons matching both criteria were classified in 2 groups: 22 neurons changed their firing rate during spontaneous horizontal eye movements (EM-neurons), 17 modulated their activity only during head rotation and were labeled vestibular-only neurons (VO-neurons). 5. Sufficient data were obtained from 13 EM-neurons to allow a quantitative analysis. Among those, 12 were activated from the contralateral and 1 from the ipsilateral flocculus. Their sensitivity to horizontal eye position during intersaccadic fixation was 3.54 +/- 2.75 (SD) spikes.s-1/deg. Eight EM-neurons behaved as type I neurons, five as type II neurons. During the slow phases of the VOR, all of these neurons combined some head-velocity sensitivity (1.50 +/- 0.43 spikes.s-1/deg.s-1) with some horizontal eye-position sensitivity (3.61 +/- 2.45 spikes.s-1/deg). Additionally, seven of these neurons presented a sensitivity to eye velocity (1.34 +/- 0.55 spikes.s-1/deg.s-1). The phase difference between the modulation of firing rate and eye position varied substantially between neurons. The observed phase lead with respect to eye position ranged from 2 to 110 degrees (41.9 +/- 31.8 degrees). 6. Sufficient data were obtained from 10 VO-neurons to allow a quantitative analysis. Among those, nine were activated from the contralateral and one from the ipsilateral flocculus. All of these neurons behaved as type I neurons. The sensitivity to head velocity was 1.64 +/- 1.07 spikes.s-1/deg.s-1. The phase lead of the modulation of spike activity with respect to head velocity ranged from 4.5 to 30.5 degrees (16.4 +/- 8.9 degrees). 7. We conclude that the MVN provides the horizontal zone of the flocculus (with a strong contralateral preference) with information about head velocity (through VO-neurons and EM-neurons) and about eye velocity and position (through EM-neurons).

Animals↗
PubMedDate not supplied

Vestibulo-thalamic projections studied with antidromic technique in the cat.

The vestibulo-thalamic projection was investigated in anaesthetized cats. Electrical stimulation of posterolateral thalamic areas frequently changed the spontaneous firing pattern of neurons in the vestibular nuclei but only 5% were antidromically invaded. This group was further analysed with regard to types of labyrinthine and somatosensory input; thalamo-projecting neurons in the vestibular nuclei are frequently located in the lateral vestibular nucleus, they receive no monosynaptic inflow from the labyrinth and they often receive convergent vestibular and somatosensory input.

Animals↗
PubMed2003

Brain stem pursuit pathways: dissociating visual, vestibular, and proprioceptive inputs during combined eye-head gaze tracking.

Eye-head (EH) neurons within the medial vestibular nuclei are thought to be the primary input to the extraocular motoneurons during smooth pursuit: they receive direct projections from the cerebellar flocculus/ventral paraflocculus, and in turn, project to the abducens motor nucleus. Here, we recorded from EH neurons during head-restrained smooth pursuit and head-unrestrained combined eye-head pursuit (gaze pursuit). During head-restrained smooth pursuit of sinusoidal and step-ramp target motion, each neuron's response was well described by a simple model that included resting discharge (bias), eye position, and velocity terms. Moreover, eye acceleration, as well as eye position, velocity, and acceleration error (error = target movement - eye movement) signals played no role in shaping neuronal discharges. During head-unrestrained gaze pursuit, EH neuron responses reflected the summation of their head-movement sensitivity during passive whole-body rotation in the dark and gaze-movement sensitivity during smooth pursuit. Indeed, EH neuron responses were well predicted by their head- and gaze-movement sensitivity during these two paradigms across conditions (e.g., combined eye-head gaze pursuit, smooth pursuit, whole-body rotation in the dark, whole-body rotation while viewing a target moving with the head (i.e., cancellation), and passive rotation of the head-on-body). Thus our results imply that vestibular inputs, but not the activation of neck proprioceptors, influence EH neuron responses during head-on-body movements. This latter proposal was confirmed by demonstrating a complete absence of modulation in the same neurons during passive rotation of the monkey's body beneath its neck. Taken together our results show that during gaze pursuit EH neurons carry vestibular- as well as gaze-related information to extraocular motoneurons. We propose that this vestibular-related modulation is offset by inputs from other premotor inputs, and that the responses of vestibuloocular reflex interneurons (i.e., position-vestibular-pause neurons) are consistent with such a proposal.

Action Potentials↗
PubMed1990

[Localization of calcitonin gene-related peptide-like immunoreactivities in the vestibular nuclei of the rat by light and electron microscopic studies].

The distribution and fine structure of calcitonin gene-related peptide-like immunoreactive (CGRP-LI) cells and fibers in the vestibular nuclei of the rat were investigated by light and electron microscopic immunocytochemistry. In addition to the previous report that CGRP-LI cells were found in the lateral vestibular nucleus, the present study clarified that they are found also in the inferior vestibular nucleus, medial vestibular nucleus and nucleus X. The lateral vestibular nucleus contains a high density of CGRP-LI cells. They are medium in size and multipolar in shape. CGRP-LI cells in the inferior vestibular nucleus are small to medium in size and triangular or pea shaped. CGRP-LI cells in the medial vestibular nucleus and nucleus X are both few in number and small in size. Possible colocalization of CGRP with acetylcholine, gamma-aminobutyric acid or substance P in the single neuron of the vestibular nuclei might be suggested. CGRP-LI fibers are more extensively distributed in various areas throughout the vestibular nuclei, though previous studies reported that they were found in the lateral vestibular nucleus and inferior vestibular nucleus. A number of CGRP-LI fibers are clearly observed in the inferior vestibular nucleus. Under electron microscopic analysis, CGRP-LI endoproducts are diffusely localized throughout the cytoplasm and some of CGRP-LI dendrites are identified to receive synaptic inputs form non-immunoreactive axon terminals with small spherical vesicles. It seems likely that CGRP is participated both in the intrinsic neurons in the vestibular nuclei or in the reciprocal innervations between the vestibular nuclei and the reticular formation or the cerebellum.

Animals↗
PubMed2003

Role of Phox2b and Mash1 in the generation of the vestibular efferent nucleus.

The inner ear (vestibular and cochlear) efferent neurons are a group of atypical motor-like hindbrain neurons which innervate inner ear hair cells and their sensory afferents. They are born in the fourth rhombomere, in close association with facial branchial motor neurons, from which they subsequently part through a specific migration route. Here, we demonstrate that the inner ear efferents depend on Phox2b for their differentiation, behaving in that respect like hindbrain visceral and branchial motor neurons. We also show that the vestibular efferent nucleus is no longer present at its usual site in mice inactivated for the bHLH transcription factor Mash 1. The concomitant appearance of an ectopic branchial-like nucleus at the location where both inner ear efferents and facial branchial motor neurons are born suggests that Mash1 is required for the migration of a subpopulation of rhombomere 4-derived efferents.

Animals↗
PubMed1983

Direct projections from vestibular nuclei to facial nucleus in cats.

Postsynaptic potentials were recorded from motoneurons in the facial nucleus in response to stimulation of the vestibular and trigeminal nerves. The motoneurons were identified by antidromic activation from their peripheral axons. Disynaptic excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) and mixed EPSP/IPSPs were recorded in response to vestibular nerve stimulation, ranging in latency from 0.9 to 2.1 ms, with most at 1.5 ms. Activity in secondary vestibular axons recorded within the facial nucleus occurred at a latency of 0.7-1.1 ms. The amplitudes of the vestibular postsynaptic potentials were small, generally less than a millivolt, but double shocks produced marked summation. The average time to peak of ipsilateral vestibular EPSPs, 1.1 ms, was faster than that of either ipsilateral IPSPs, 1.6 ms, or contralateral EPSPs, 1.4 ms. The double-spiked vestibular activity was detectable in double-peaked PSPs. Disynaptic EPSPs, ranging in latency from 2.0 to 3.0 ms, were recorded in response to trigeminal nerve stimulation. The average time to peak was 1.3 ms. The multiple-spiked activity of the trigeminal neurons was detectable in multipeaked EPSPs. Inhibitory ipsilateral effects (Vi IPSPs) were recorded twice as often as excitatory ipsilateral effects (Vi EPSPs), being found in 29% versus 15% of the motoneurons. Contralateral effects were found in 13% of the motoneurons studied, and almost all were excitatory. Analysis of synaptic potential shapes suggested that the excitatory and inhibitory vestibular synapses probably contact distal dendrites preferentially, with the excitatory connections being somewhat closer to the soma. The trigeminal inputs probably contact the facial motoneurons more extensively near the soma. Horseradish peroxidase was injected into the facial nucleus, and retrograde uptake by vestibular neurons was studied. The majority of filled vestibular neurons was ipsilateral to the injection site, especially in the medial vestibular nucleus, ventral y group, and supravestibular nucleus. On the contralateral side, filled vestibular cells were found almost exclusively in the medial nucleus. Filled cells were also noted in the trigeminal nucleus, predominantly ipsilaterally at all rostrocaudal levels. We have demonstrated monosynaptic projections to facial motoneurons from both vestibular and trigeminal nuclei. The trigeminal input is likely to be involved in facial reflexes, especially blinking and grimacing. The afferent vestibular population overlaps that going to the oculomotor and cervical motoneurons; these projections may be collaterals of single vestibular neurons.4+.

Animals↗
PubMed1989

Chromatin changes in frog neurons after eighth nerve transection.

Fourteen days after unilateral eighth nerve transection in the frog, Purkinje neurons of the lobus vestibulolateralis and corpus of the cerebellum and medium-sized neurons of the vestibular nuclear complex showed changes in metabolic activity. In the ipsilateral parts, and to a lesser extent in the contralateral parts, of operated frogs, the Feulgen-DNA values were higher and the nuclear areas larger, associated with decondensation of chromatin. The cytoplasmic basophilia was also less. These changes could be due to anabolic responses of the neuronal populations during regeneration. The anabolic reaction of the corpus cerebelli and contralateral vestibular nuclear complex is only partially non-specific and ascribable to the surgical trauma (comparison between sham-operated and unoperated frogs). The results indicate clear patterns of connection between the ipsilateral and contralateral parts and between the cerebellar and vestibular nuclear complex neurons.

Animals↗
PubMed1994

Medium-lead burst neurons related to vertical saccades in cat Forel's field H: input from vestibular nucleus.

The present study was undertaken to investigate synaptic connections between medium-lead burst neurons (MLBNs) related to vertical saccades in Forel's field H and vestibular nucleus (VN) neurons. Extracellular spikes were recorded from single MLBNs and their responses to VN stimulation were examined using chronically prepared alert cats. Twenty of 30 upward MLBNs and 10 of 22 downward MLBNs could be synaptically activated mainly by the ipsilateral VN stimulation with spike latencies of 2.2-12.0 and 1.9-11.7 ms, respectively. These results suggest that there exist di- or polysynaptic connections which transfer velocity signals for vertical saccades from the ipsilateral vestibular nucleus neurons to the vertical MLBNs.

Animals↗
PubMed1993

Recovery of head postural control following unilateral vestibular neurectomy in the cat. Neck muscle activity and neuronal correlates in Deiters' nuclei.

Recovery of head postural control after unilateral vestibular neurectomy was investigated in the alert cat by chronically recording the spontaneous neck muscle EMG activity from splenius capitis on both sides and the vestibulocollic reflexes evoked during roll and pitch tilts. Neuronal correlates occurring within the lateral (Deiters) vestibular nuclei (LVN) were also recorded during the time-course of recovery. During the acute phase (1-2 weeks), the cats exhibited strong imbalance in spontaneous neck muscle activity, characterized by increased muscular tone in the ipsilateral splenius capitis muscle and hypoactivity in the contralateral one. At the same time, the mean resting activity of Deiters' neurons strongly decreased on the deafferented side, while a slight but significant decrease was observed on the intact side. Vestibulocollic reflexes were totally lacking during the acute phase, whatever the direction and the amplitude of tilt. Recovery developed in the following weeks, leading to complete rebalance of spontaneous EMG activity as well as near to normal static vestibulocollic reflexes 5 weeks after the lesion. However, compensation remained sub-normal during roll tilts while overcompensation was found during pitch tilts, suggesting that the intact labyrinth would play a leader role in the recovery process but that bilateral cooperation of the two labyrinths is required for proper head postural control. Five weeks are also needed for a partial rebalancing of resting activity between both LVN. These results indicate that changes in neck muscle activity observed in the acute cats and that recovery found in the compensated animals could result from modifications in neural networks controlling neck musculature, such as the LVN.

Animals↗