Unilateral Vestibular Deafferentation Research Articles

Effects of Chronic Infusion of a GABAA Receptor Agonist or Antagonist into the Vestibular Nuclear Complex on Vestibular Compensation in the Guinea Pig

The aim of this study was to determine the effects of chronic infusion of a GABA(A) receptor agonist/antagonist into the ipsilateral or contralateral vestibular nuclear complex (VNC) on vestibular compensation, the process of behavioral recovery that occurs after unilateral vestibular deafferentation (UVD). This was achieved by a mini-osmotic pump that infused, over 30 h, muscimol or gabazine into the ipsilateral or contralateral VNC. Spontaneous nystagmus (SN), yaw head tilt (YHT), and roll head tilt (RHT) were measured. Infusion of muscimol or gabazine into either the ipsilateral or the contralateral VNC had little effect on SN compensation. In contrast, infusion of muscimol (250, 500, and 750 ng) into the contralateral VNC and gabazine (31.25, 62.5, and 125 ng) into the ipsilateral VNC significantly affected YHT and RHT (p < 0.05), but not their rate of compensation (p > 0.05). Interestingly, the effects of muscimol and gabazine on YHT and RHT were consistent throughout the first 30 h post-UVD. Infusion of muscimol (62.5, 125, and 250 ng) into the ipsilateral VNC and gabazine (125, 375, and 750 ng) into the contralateral VNC had little effect on YHT and RHT or their rate of compensation. These results suggest that the ipsilateral gabazine and contralateral muscimol infusions are modifying the expression of the symptoms without altering the mechanism of compensation. Furthermore, the neurochemical mechanism responsible for vestibular compensation can cope with the both the GABA(A) receptor-mediated and the UVD-induced decrease in resting activity.

Immunocytochemical and stereological study of glucocorticoid receptors in rat medial vestibular nucleus neurons and the effects of unilateral vestibular deafferentation

Conclusion. The results of this study suggest that neither the number of medial vestibular nucleus (MVN) neurons expressing cytosolic glucocorticoid receptors nor blood corticosterone levels change significantly during the development of vestibular compensation. Objective. Vestibular compensation is a process of partial behavioral recovery that occurs following damage to the vestibular labyrinth. It has been suggested that this compensation process might be dependent on the release of glucocorticoids such as corticosterone at the time of unilateral vestibular deafferentation (UVD) and that changes in glucocorticoid receptors in the MVN might contribute to the initiation of the compensation process. Material and methods. We compared the number of MVN neurons expressing cytosolic glucocorticoid receptors in rats at 10 h and 2 weeks following UVD, and in sham and anesthetic control animals; we also measured blood corticosterone levels. Results. Using immunocytochemistry and stereology, we found that the majority of MVN neurons expressed glucocorticoid receptors, but there were no significant differences in the number of glucocorticoid receptor-expressing neurons in the ipsilateral or contralateral MVNs at 10 h or 2 weeks post-UVD; furthermore, corticosterone levels did not vary significantly between the UVD and control groups.

Cytosolic glucocorticoid receptor expression in the rat vestibular nucleus and hippocampus following unilateral vestibular deafferentation

It has been suggested that vestibular compensation, the process of behavioural recovery that occurs following peripheral vestibular damage, might be partially dependent on the release of glucocorticoids (GC) during the early stages of recovery from the lesion. One possibility is that glucocorticoid receptors (GRs) in the vestibular nucleus complex (VNC) might change following the lesion, altering their response to GCs. We sought to test this hypothesis by quantifying the expression of cytosolic GRs in the bilateral VNCs at 10 h, 58 h and 2 weeks following unilateral vestibular deafferentation (UVD) in rat, using western blotting. We also examined GR expression in the CA1, CA2/3 and dentate gyrus (DG) subregions of the hippocampus and measured serum corticosterone levels. Compared with sham surgery and anaesthetic controls, we found no significant changes in GR expression in the ipsilateral or contralateral VNCs at any time post-UVD. However, we did find a significant decrease in GR expression in the ipsilateral CA1 at 2 weeks post-UVD. Serum corticosterone levels were significantly lower in all groups at 58 h post-op. compared to 10 h and 2 weeks; however, there were no significant differences between the UVD and control groups at any time point. These results suggest that changes in GR expression in the VNC are unlikely to contribute to the development of vestibular compensation. However, long-term changes in GR expression in CA1 might be related to chronic deficits in hippocampal function and spatial cognition following vestibular damage.

Nitric oxide synthase and arginase expression changes in the rat perirhinal and entorhinal cortices following unilateral vestibular damage: A link to deficits in object recognition?

Previous studies have shown that peripheral vestibular damage causes long-term neurochemical changes in the hippocampus which may be related to spatial memory deficits. Since recent studies have also demonstrated deficits in non-spatial object recognition memory following vestibular lesions, the aim of the present study was to extend these investigations into the perirhinal cortex (PRC), which is known to be important for object recognition, and the related entorhinal cortex (EC). We examined the effects of unilateral vestibular deafferentation (UVD) on the expression of four enzymes associated with neuronal plasticity, neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS), arginase I and arginase II (AI and II), in the rat EC and PRC using Western blotting. Tissue was collected at 10 hs, 50 hs and 2 weeks post-UVD. In the EC and PRC, nNOS protein expression decreased on the contralateral side at 2 weeks post-UVD but not before. At the same time, eNOS protein expression increased in both regions on the contralateral side. In the EC, AII protein expression increased on the ipsilateral side at 2 weeks post-UVD. In the PRC, AI increased and decreased on the contralateral and ipsilateral sides (respectively) at 2 weeks post-UVD. AII showed a bilateral increase in the PRC at 2 weeks post-UVD. These results demonstrate changes in NOS and arginase protein expression in the PRC and EC following UVD, which are unlikely to be due to the initial severity of the vestibular syndrome because they develop well after vestibular compensation has taken place. Neurochemical changes in these regions of the medial temporal lobe may be implicated in the development of object recognition deficits that contribute to cognitive dysfunction following peripheral vestibular damage.

Microarray analysis of gene expression in the rat vestibular nucleus complex following unilateral vestibular deafferentation

To investigate the molecular background of vestibular compensation, a model of lesion-induced plasticity, we used a microarray analysis to examine genes that show asymmetrical expression between the bilateral vestibular nucleus complexes (VNCs) 6 h following unilateral vestibular deafferentation (UVD). Asymmetrical gene expression was then validated by a real-time quantitative PCR. Among the 88 genes for which the ipsilateral (ipsi) : contralateral (contra) was > 1.35, the number of known genes was 33 (38%), and the number of expressed sequence tag (EST) sequences was 55 (62%). Among the 130 genes for which the contra : ipsi was > 1.35, the number of known genes was 55 (42%), and the number of EST sequences was 75 (58%). Changes in some of the genes were consistent with previous studies; however, we found several new genes which could be functionally related to the molecular basis of the electrophysiological asymmetry between the VNCs following UVD. Ipsi > contra genes included the GABA(A) receptor rho subunit, regulatory proteins of G protein signaling, calcium signaling related molecules such as the voltage-dependent calcium channel alpha2/delta subunit 1, calcineurin subunit Abeta and Ca(2+) pump. Contra > ipsi genes included the neuronal high affinity glutamate transporter, 5-hydroxytryptamine receptor 1D, mitogen-activated protein kinase 12 and ubiquitin carboxy-terminal hydrolase L1.

Initiation and cancellation of the human heave linear vestibulo-ocular reflex after unilateral vestibular deafferentation

The effect of unilateral vestibular deafferentation (UVD) on the linear vestibulo-ocular reflex (LVOR) was studied in 11 humans an average of 52 months following surgical UVD. Controls consisted of seven healthy age-matched subjects. The LVOR was evoked by directionally random, transient whole body interaural (heave) translation with a peak acceleration of 0.5 g while subjects viewed earth-fixed (LVOR) and head-fixed (cancellation) targets 15, 25, and 200 cm distant. The magnitude of the LVOR slow phase was inversely proportional to target distance for both subject groups. Neither latency nor the magnitude of the LVOR significantly differed in the ipsi- vs contralesional directions (P>0.1) in UVD. When the target disappeared at heave onset, subjects with UVD had LVOR slow phase displacement 100 ms later that was 5% of ideal at 15 cm, 6% at 25 cm, and 16% at 200 cm. This was significantly less than corresponding control values of 41, 43, and 50%. During cancellation the LVOR magnitude 100 ms from heave onset was reduced at all target distances by an average of 40+/-4%, and the relative reduction did not significantly differ between controls and subjects with UVD (P>0.1). Cancellation latency did not vary significantly among target distances or subject groups. It is concluded that after UVD, the LVOR is bilaterally and symmetrically reduced but remains modulated by viewing distance and cancellation effort.

Immunohistochemical characterisation and localisation of cannabinoid CB1 receptor protein in the rat vestibular nucleus complex and the effects of unilateral vestibular deafferentation

CB1 receptor expression has been reported to be low in the brainstem compared with the forebrain, and low in the vestibular nucleus complex (VNC) compared with other regions in the brainstem. However, a frequent effect of cannabis is dizziness and loss of balance. This may be due to the activation of cannabinoid receptors in the central vestibular pathways. We used immunohistochemistry to study the distribution of CB1 receptor protein in the VNC, and Western blotting to measure CB1 receptor expression in the VNC following unilateral vestibular deafferentation (UVD); the hippocampal CA1, CA2/3 and dentate gyrus (DG) regions were also analysed for comparison. This study confirms a previous electrophysiological demonstration that CB1 receptors exist in significant densities in the VNC and are likely to contribute to the neurochemical control of the vestibular reflexes. Nonetheless, CB1 receptor expression did not change significantly in the VNC during vestibular compensation. In addition, despite some small but significant changes in CB1 receptor expression in the CA2/3 and the DG following UVD, in no case were these differences statistically significant in comparison to both control groups.

11β-Hydroxysteroid Dehydrogenase Type 1 Activity in Medial Vestibular Nucleus and Cerebellum after Unilateral Vestibular Deafferentation in the Rat

In the early stages of vestibular compensation (VC) (the behavioural recovery that follows unilateral vestibular deafferentation), neurons in the medial vestibular nucleus (MVN) on the lesioned side develop a sustained up-regulation of their intrinsic excitability. This plasticity is dependent on the activation of glucocorticoid receptors, which presumably occurs during the acute stress response that accompanies the vestibular deafferentation symptoms. Recent studies have established that the access of glucocorticoids to their intracellular receptors in brain is potently modulated by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which catalyses the generation of active glucocorticoids from their inert 11-keto forms. In this study, we investigated the presence of 11β-HSD1 bioactivity, and possible changes in activity in the early stage after vestibular deafferentation, in the cerebellar nodulus and uvula, the flocculus/paraflocculus (F/PF) complex and the MVN of the rat. 11β-HSD1 activity was found in each of these brain areas, with especially high levels of activity in the F/PF complex. No differences were found in the level of 11β-HSD1 activity in these brain areas between control rats, sham-operated rats and rats that underwent VC for 4 h after unilateral vestibular deafferentation. These findings demonstrate 11β-HSD1 bioactivity in the MVN and vestibulocerebellum, but exclude the possibility that changes in 11β-HSD1 activity occur in the early period after deafferentation, over the time when changes in MVN neuronal properties take place.

Idiosyncratic compensation of the subjective visual horizontal and vertical in 60 patients after unilateral vestibular deafferentation

ObjectiveTo investigate long-term compensation mechanisms of utricular function after translabyrinthine surgery for vestibular schwannoma. Correlations between the subjective visual horizontal (SVH) and subjective visual vertical (SVV) and other parameters of vestibular compensation were studied. The correlation between the SVH and SVV was also investigated to see whether these measurements are compatible for patients.Material and MethodsSixty consecutive patients were investigated 3 months before and 6 months after surgery by means of electronystagmography and SVH and SVV tests. Tumor size was measured using MRI.ResultsThe SVH and SVV increased significantly towards the ipsilesional side postoperatively. Preoperative tilt correlated with age. Postoperative tilt correlated weakly with preoperative caloric sensitivity and inversely with tumor size. The correlation between the SVH and SVV was high both before and after surgery (rs>0.74; p<0.001).ConclusionsThe long-term compensation of static tilt perception was dependent on age and not on dynamic canal functions. We propose an idiosyncrasy in the SVH and SVV compensation after unilateral vestibular deafferentation, incongruous with the general course of vestibular compensation. The results suggest a probable dependence on non-vestibular information, i.e. proprioception, in facilitating compensation of static vestibular deficits. The similarity between the SVH and SVV measurements confirms that either test can be used clinically for patients with vestibular lesions.

Vestibular testing by electrical stimulation in patients with unilateral vestibular deafferentation: galvanic evoked myogenic responses testing versus galvanic body sway testing.

To investigate the agreement of a lesion site as indicated by two different vestibular tests with electrical stimulation, galvanic body sway testing (GBST) and galvanic evoked myogenic responses (galvanic vestibular evoked myogenic potential; galvanic VEMP) testing, in patients with unilateral vestibular deafferentation. Nineteen patients with unilateral vestibular deafferentation were studied, and the criteria for patient selection were as follows: (1) absence of a caloric response to ice water on the affected side in a supine position, and (2) absence of VEMP to 95 dBnHL clicks on the affected side. We assessed the postural response of the subjects to long duration galvanic stimulation (1 mA, 5 s) by measuring the lateral displacement at the center of foot pressure with a cathode electrode on the forehead, and an anode electrode on the mastoid (GBST). We also recorded the electromyographic (EMG) activities of the sternocleidomastoid muscle (SCM) to short duration galvanic stimulation (3 mA, 1 ms) (galvanic VEMP) with a cathode electrode on the mastoid, and an anode electrode on the forehead. In 18 of the 19 patients, the lesion site indicated by GBST was identical to that indicated by galvanic VEMP. Fourteen patients had abnormal results in both tests while 4 patients had normal results in both tests. One patient with acoustic neuroma had normal results in GBST but abnormal results in galvanic VEMP. These results suggest that electrical stimulation in these two tests stimulates the same area of the peripheral vestibular afferent system, although the duration of stimulation was different, and that the estimate of the lesion site indicated by these tests in patients with complete or nearly complete unilateral vestibular damages is reliable. These results suggest that short-duration galvanic stimulation as well as long-duration galvanic stimulation stimulates the vestibular system at the same level.

The human horizontal vestibulo-ocular reflex in response to active and passive head impulses after unilateral vestibular deafferentation.

We studied the compensatory eye movements made by subjects with unilateral vestibular deficits in response to passive (unpredictable, manually generated) and active (predictable, self-generated) head impulses. A typical head impulse is a brief, low-amplitude (15-20 degrees ), high-velocity (150-350 degrees /s), high-acceleration (4000-6000 degrees /s(2)), yaw head-on-trunk rotation. In the initial 75 ms of the response, the vestibulo-ocular reflex gain was significantly higher during active head impulses to both ipsilesional and contralesional sides, than during passive impulses. Mean gains were 0.15 (ipsilesional passive), 0.44 (ipsilesional active), 0.5 (contralesional passive), and 0.76 (contralesional active). Differences between active and passive head impulses were present from near the onset of head rotation. The mechanism for producing this behavior is unclear, but the findings could be related to enhanced sensitivity of second-order neurons during active head impulses. However, even with active movements, there is still a large and statistically significant asymmetry in the eye-movement responses for ipsilesional as opposed to contralesional head rotations. After 75 ms, rapid corrective eye movements often were generated to reduce any remaining gaze error.

Vestibular catch-up saccades augmenting the human transient heave linear vestibulo-ocular reflex.

Vestibular catch-up saccades (VCUS) cued by the semicircular canals can supplement the deficient angular vestibulo-ocular reflex during transient rotations to stabilize gaze in people with unilateral vestibular deafferentation (Tian et al. 2000). However, a possible analogous role for VCUS to augment a deficient linear vestibulo-ocular reflex (LVOR) has not been carefully studied. We investigated VCUS in 9 younger, 8 older normal, and 12 vestibulopathic subjects undergoing directionally random heave (interaural) translations at 0.5 g peak acceleration. Eye and head movements were sampled at 1200 Hz using magnetic search coils and a cranial accelerometer. Subjects fixated visible targets 200, 50, or 15 cm distant immediately before unpredictable onset of translation in either darkness or light. Evoked slow phase eye rotations opposite to the direction of head translation accounted for only 19-70% of ideal eye position, being less for nearer targets, and VCUS commonly occurred to augment the deficiency. Eye position error relative to geometric ideal was highly correlated to VCUS amplitude ( P<0.001). This error was systematically corrected by VCUS whose latency decreased, and speed and frequency increased, with decreasing target distance. When targets remained visible, nearly all subjects made VCUS for nearer targets. In darkness, VCUS for the nearest target were significantly less common for older normal and vestibulopathic subjects than in younger normal subjects ( P<0.001). In older and vestibulopathic subjects, VCUS latency was significantly prolonged. We conclude that otolith-mediated VCUS calibrated to target distance assist LVOR slow phases, but the ability to generate VCUS in darkness is impaired in older normal and vestibulopathic subjects. In the presence of visual information, VCUS can be generated in older and vestibulopathic subjects, albeit at prolonged latency perhaps indicating visual augmentation of deficient vestibular input.

Effect of Low Body Temperature During Unilateral Labyrinthectomy on Vestibular Compensation in the Guinea Pig

Objectives - Vestibular compensation, the recovery that follows unilateral vestibular deafferentation (UVD), is a model for central nervous system plasticity. Recovery from the static symptoms of UVD may involve temperature-dependent processes that modulate the immediate effects of UVD and/or the capability of the central nervous system to undergo adaptive plasticity. In this study we investigated changes in oculomotor and postural vestibular symptoms resulting from low body temperature during UVD. Material and methods - To study the effect of low temperatures at the time of UVD on vestibular compensation, we compared the rate of compensation and peak values for postural [roll head tilt (RHT) and yaw head tilt (YHT)] and oculomotor [spontaneous nystagmus (SN)] symptoms in three groups of guinea pigs. Animals in Group 1 (n=6) were maintained at 38°C throughout unilateral labyrinthectomy (UL). Animals in Group 2 (n=6) were not temperature-controlled and animals in Group 3 (n=4) were cooled with ice to 25°C throughout UL. Results - Cooled animals showed significantly higher rates of SN upon recovery from anaesthesia and took a significantly longer time to compensate. Cooled animals were also slower to compensate for postural symptoms (RHT and YHT), with 2 animals showing no compensation for RHT 52 h after UL. Conclusion - Hypothermia (25°C) during UVD surgery exacerbates postural and oculomotor symptoms following UL and significantly slows recovery.

Vibration-induced ocular torsion and nystagmus after unilateral vestibular deafferentation.

Vibration is an excitatory stimulus for both vestibular and proprioceptive afferents. Vibration applied either to the skull or to the neck muscles of subjects after unilateral vestibular deafferentation induces nystagmus and a shift of the subjective visual horizontal. Previous studies have ascribed these effects to vibratory stimulation of neck muscle proprioceptors. Using scleral search coils, we recorded three-dimensional eye movements during unilateral 92 Hz vibration of the mastoid bone or of the sternocleidomastoid (SCM) muscle in 18 subjects with chronic unilateral vestibular deficits after vestibular neurectomy or neuro-labyrinthitis. Nine subjects had lost function of all three semicircular canals (SSCs) on one side, and the other nine had lost function of only the anterior and lateral SSCs. Vibration of the mastoid bone or of the SCM muscle on either side induced an ipsilesional tonic shift of torsional eye position of up to 6.5 degrees during visual fixation, as well as a nystagmus with horizontal, vertical and torsional components in darkness. Subjects who had lost function of all three SSCs on one side showed a larger shift in ocular torsion in response to SCM vibration than did subjects who had lost function of only two SSCs. The difference between ocular torsion produced by ipsilesional muscle or bone vibration was not significantly different from that produced by contralesional bone or muscle vibration. The vibration-induced nystagmus rotation axis tended to align with the pitch (y) axis of the head in subjects who had lost only anterior and lateral SSC function, and with the roll (x) axis of the head in subjects who had lost function of all three SSCs. We propose that the previously described vibration-induced shift of the subjective visual horizontal can be explained by the vibration-induced ocular torsion, and that the magnitude of ocular torsion is related to the extent of the unilateral vestibular deficit. While altered proprioceptive inputs from neck muscles might be important in the mechanism of vibration-induced ocular torsion and nystagmus after unilateral vestibular deafferentation, vibratory stimulation of vestibular receptors in the intact labyrinth also appears to have an important role.

Long-term changes in hippocampal n-methyl- d-aspartate receptor subunits following unilateral vestibular damage in rat

Previous studies have indicated that damage to the peripheral vestibular system results in dysfunction of hippocampal place cells and an impairment of spatial learning and memory. The aim of this study was to determine whether lesions of one vestibular labyrinth (unilateral vestibular deafferentation, UVD) result in changes in the expression of the NR1 and NR2A subunits of the N-methyl- d-aspartate (NMDA) receptor, and the GluR2 subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor, in subregions of the rat hippocampus (CA1, CA2/3 and the dentate gyrus) at 10 h or 2 weeks following UVD. Compared with sham surgery controls and anaesthetic controls, the expression of the NR1 subunit was significantly reduced in the ipsilateral CA2/3 region at 2 weeks post-UVD. The expression of the NR2A subunit was also significantly reduced in the ipsilateral CA2/3 and, to a smaller extent, in the contralateral CA2/3 region, at 2 weeks post-UVD. The only other change in NR2A expression was an increase in the ipsilateral CA1 at 10 h post-UVD. No other changes in NR1, NR2A or GluR2 expression were observed in any hippocampal subregion, at any time point, or in cortical tissue at any time point. These results suggest that UVD may result in long-term changes in NMDA receptor subunit expression in the rat hippocampus.

Nitric oxide synthase and arginase expression in the vestibular nucleus and hippocampus following unilateral vestibular deafferentation in the rat

The aim of this study was to investigate the possible relationship between changes in neuronal and endothelial nitric oxide synthase (nNOS and eNOS) and arginase expression in the vestibular nucleus complex and the hippocampus (CA1, CA2/3 and the dentate gyrus (DG) at 10 h or 2 weeks following a unilateral vestibular deafferentation (UVD) in rats. There were no significant differences in nNOS or arginase II expression in the ipsilateral or contralateral VNC at either 10 h or 2 weeks post-UVD. For eNOS, there was only a significant decrease in expression in the ipsilateral VNC at 2 weeks post-UVD ( P<0.01). In the hippocampus, the only significant difference in nNOS expression was a decrease in the ipsilateral DG at 2 weeks post-UVD ( P<0.05). There was a significant decrease in eNOS expression in the contralateral CA2/3 region at 10 h post-UVD ( P<0.01). The only other significant change in eNOS was an increase in the contralateral DG at 10 h post-UVD ( P<0.01). Although arginase II was expressed in all regions of the hippocampus, there were no significant differences in arginase II expression at any time point following UVD. These results suggest that the changes in NOS expression that occur in the VNC and hippocampus following UVD are not correlated with one another or with changes in arginase II.

Effects of unilateral vestibular deafferentation on the linear vestibulo-ocular reflex evoked by impulsive eccentric roll rotation.

The effects of unilateral vestibular deafferentation (UVD) on the linear vestibulo-ocular reflex (LVOR) were studied by measuring three-dimensional eye movements in seven UVD subjects evoked by impulsive eccentric roll rotation while viewing an earth-fixed target at 200, 300, or 600 mm and comparing their responses to 11 normal subjects. The stimulus, a whole-body roll of approximately 1 degrees, with the eye positioned 815 mm eccentric to the rotation axis, produced an inter-aural linear acceleration of approximately 0.5 g and a roll acceleration of approximately 360 degrees /s(2). The responses generated by the LVOR comprise horizontal eye rotations. Horizontal eye velocity at 100 ms from stimulus onset in UVD subjects was significantly lower than in normal subjects for all viewing distances, with no significant difference between ipsilesional and contralesional responses. LVOR acceleration gain, defined as the slope of actual horizontal eye velocity divided by the slope of ideal horizontal eye velocity during a 30-ms period starting 70 ms from stimulus onset, was bilaterally significantly reduced in UVD subjects at all viewing distances. Acceleration gain from all viewing distances was 1.04 +/- 0.28 in normal subjects, and in UVD subjects was 0.49 +/- 0.23 for ipsilesional and 0.63 +/- 0.27 for contralesional acceleration. LVOR enhancement in the first 100 ms by near viewing was still present in UVD subjects. LVOR latency in UVD subjects (approximately 39 ms) was not significantly different from normal subjects (approximately 36 ms). After UVD, LVOR is bilaterally and largely symmetrically reduced, but latency remains unchanged and modulation by viewing distance is still present.

A realistic neural-network simulation of both slow and quick phase components of the guinea pig VOR.

A realistic neural-network model was constructed to simulate production of both the slow-phase and quick-phase components of vestibular nystagmus by incorporating a quick-phase pathway into a previous model of the slow phase. The neurons in the network were modelled by multicompartmental Hodgkin-Huxley-style spiking neurons based on known responses and projections of physiologically identified vestibular neurons. The modelling used the GENESIS software package. The slow-phase network consisted of ganglion and medial vestibular nucleus (MVN) neurons; the latter were constructed using biophysical models of MVN type A and B neurons. The quick-phase network contained several types of bursting cells which have been shown to have major roles in the generation of the quick phase: burster-driver neurons, long-lead burst neurons, pause neurons, excitatory burst neurons and inhibitory burst neurons. Comparison of the output neural responses from the model with guinea pig behavioural responses from the companion paper showed consistency between model and animal data for neuron firing patterns, maximal firing rates, and timing, duration and number of quick phases. Comparisons were made for stable head input and for sinusoidal angular stimuli at a range of frequencies from 0.1 to 2 Hz. Except for data at 0.1 Hz, where the simulation produced one more quick phase per half cycle than the animal data, the number of quick phases was consistent between the model and the animal data. The model was also used to simulate the effects both of unilateral vestibular deafferentation (UVD) and of vestibular compensation after UVD, and the responses in the modelled MVN neurons were affected in a way similar to those measured in guinea pig MVN neurons: the number of quick phases and their timing changed in a similar fashion to that observed in behavioural data.

Activation of the hypothalamic–pituitary–adrenal axis following vestibular deafferentation in pigmented guinea pig

Twelve male pigmented guinea pigs underwent either a unilateral vestibular deafferentation (UVD) ( n=6) or sham operation ( n=6). Compared to the pre-operated salivary cortisol concentrations, the UVD operation resulted in a significant increase in night cortisol concentrations ( P<0.05) and a significant interaction between the night cortisol concentration and time ( P<0.05). There was no significant difference between the pre- and post-UVD morning salivary cortisol concentrations; nor between the pre- and post-sham morning or night salivary cortisol concentrations. This study suggests that the ocular–motor and postural syndrome is causing the activation of the hypothalamic–pituitary–adrenal (HPA) axis.

NMDA and AMPA receptor subunit protein expression in the rat vestibular nucleus following unilateral labyrinthectomy.

We examined the expression of the NR1 and NR2A subunits of the N-methyl-D-aspartate (NMDA) receptor, and the GluR2 subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor, in the ipsilateral and contralateral vestibular nucleus complexes (VNCs) at 10 h and 2 weeks following unilateral vestibular deafferentation (UVD) in rats, in order to directly test the hypothesis that the behavioural recovery following UVD ('vestibular compensation') is associated with an up-regulation of NMDA receptors. We found no significant changes in NR1 or NR2A expression at 10 hs or 2 weeks post-op. compared to sham and anesthetic controls. We did find a significant (p < 0.01 and p < 0.05) increase in GluR2 expression in both VNCs at 10 h but not 2 weeks post-op. compared to sham and anesthetic controls; however, comparison over time post-UVD failed to detect a significant difference, suggesting that it was small and transient at best. These results add further evidence to the conclusion that NMDA receptors do not undergo up-regulation in the ipsilateral VNC during vestibular compensation.