Asymmetric vestibular stimulation reveals persistent disruption of motion perception in unilateral vestibular lesions.

Self-motion perception was studied in patients with unilateral vestibular lesions (UVL) due to acute vestibular neuritis at 1 wk and 4, 8, and 12 mo after the acute episode. We assessed vestibularly mediated self-motion perception by measuring the error in reproducing the position of a remembered visual target at the end of four cycles of asymmetric whole-body rotation. The oscillatory stimulus consists of a slow (0.09 Hz) and a fast (0.38 Hz) half cycle. A large error was present in UVL patients when the slow half cycle was delivered toward the lesion side, but minimal toward the healthy side. This asymmetry diminished over time, but it remained abnormally large at 12 mo. In contrast, vestibulo-ocular reflex responses showed a large direction-dependent error only initially, then they normalized. Normalization also occurred for conventional reflex vestibular measures (caloric tests, subjective visual vertical, and head shaking nystagmus) and for perceptual function during symmetric rotation. Vestibular-related handicap, measured with the Dizziness Handicap Inventory (DHI) at 12 mo correlated with self-motion perception asymmetry but not with abnormalities in vestibulo-ocular function. We conclude that 1) a persistent self-motion perceptual bias is revealed by asymmetric rotation in UVLs despite vestibulo-ocular function becoming symmetric over time, 2) this dissociation is caused by differential perceptual-reflex adaptation to high- and low-frequency rotations when these are combined as with our asymmetric stimulus, 3) the findings imply differential central compensation for vestibuloperceptual and vestibulo-ocular reflex functions, and 4) self-motion perception disruption may mediate long-term vestibular-related handicap in UVL patients.NEW & NOTEWORTHY A novel vestibular stimulus, combining asymmetric slow and fast sinusoidal half cycles, revealed persistent vestibuloperceptual dysfunction in unilateral vestibular lesion (UVL) patients. The compensation of motion perception after UVL was slower than that of vestibulo-ocular reflex. Perceptual but not vestibulo-ocular reflex deficits correlated with dizziness-related handicap.

Perceived state of self during motion can differentially modulate numerical magnitude allocation.

Although a direct relationship between numerical allocation and spatial attention has been proposed, recent research suggests that these processes are not directly coupled. In keeping with this, spatial attention shifts induced either via visual or vestibular motion can modulate numerical allocation in some circumstances but not in others. In addition to shifting spatial attention, visual or vestibular motion paradigms also (i) elicit compensatory eye movements which themselves can influence numerical processing and (ii) alter the perceptual state of 'self', inducing changes in bodily self-consciousness impacting upon cognitive mechanisms. Thus, the precise mechanism by which motion modulates numerical allocation remains unknown. We sought to investigate the influence that different perceptual experiences of motion have upon numerical magnitude allocation while controlling for both eye movements and task-related effects. We first used optokinetic visual motion stimulation (OKS) to elicit the perceptual experience of either 'visual world' or 'self'-motion during which eye movements were identical. In a second experiment, we used a vestibular protocol examining the effects of perceived and subliminal angular rotations in darkness, which also provoked identical eye movements. We observed that during the perceptual experience of 'visual world' motion, rightward OKS-biased judgments towards smaller numbers, whereas leftward OKS-biased judgments towards larger numbers. During the perceptual experience of 'self-motion', judgments were biased towards larger numbers irrespective of the OKS direction. Contrastingly, vestibular motion perception was found not to modulate numerical magnitude allocation, nor was there any differential modulation when comparing 'perceived' vs. 'subliminal' rotations. We provide a novel demonstration that numerical magnitude allocation can be differentially modulated by the perceptual state of self during visual but not vestibular mediated motion.

Balance control impairment induced after OKS in patients with vestibular migraine: an intercritical marker.

The aim of the study was to assess the effects of optokinetic stimulation (OKS) on vestibular postural control in migraine patients with recurrent vertigo. 15 patients with vestibular migraine (VM) were enrolled in a posturographic study in eyes open (OE) and eyes closed (CE) condition. The tests were performed between attacks of headache and vertigo at three different time: before, during, and 60 min after OKS. Data of patients with VM were compared with those obtained from two control groups matched for sex and age (15 for each group): (a) normal subjects not suffering from migraine without history of recurrent vertigo (N group); (b) subjects suffering from migraine with no history of recurrent vertigo (M group). Mean sway path velocity and sway area were analyzed. OKS increased the instability in all groups during the stimulus, and both the velocity and area values were higher in M and VM group. However, there was not significant difference between these two groups when stability was examined in OE condition before, during and after OKS stimulation. Conversely, in CE condition a significant greater instability was induced after OKS stimulation only in VM. In particular, post-stimulus values were significantly higher than the pre-stimulus one only in this group, while no significant difference was observed in other groups. A spatial analysis of the sway area evidenced that the instability induced by the OKS in VM group occurred along the direction of OKS. We suggest that this enhanced instability observed after OKS during the intercritical period may be considered an useful marker to support the diagnostic definition of VM in the absence of other vestibular signs.

Effects of focal vibration on bone mineral density and motor performance of postmenopausal osteoporotic women.

AIM: This randomized double blind controlled study is aimed at determining the effect of repeated vibratory stimuli focally applied to the contracted quadriceps muscles (repeated muscle vibration=rMV) on bone mineral density, leg power and balance of postmenopausal osteoporotic women. METHODS: The study has been conducted on 40 voluntary postmenopausal osteoporotic women, randomised at 2 groups for rMV treatment and for control. The treatment group underwent rMV (100Hz, 300-500 µm; three applications per day, each lasting 10-minutes, for 3 consecutive days) applied to voluntary contracted quadriceps (VC=vibrated and contracted group). The control group, received a sham stimulation on contracted quadriceps (NV=non vibrated group). Bone mineral density T-score of proximal femur of the participants, was evaluated in two weeks before and 360 days after intervention; body balance and explosive leg power were measured 1 day before, 30 days and 360 days after treatment. RESULTS: VC group T-score at one year didn't change significantly relative to baseline values (pretreatment: -2.61±0.11, post-treatment -2.62±0.13); conversely in NV subjects T-score decreased significantly from -2.64 ± 0.15 SD down to -2.99 ± 0.28 SD. A significant improvement of balance and explosive leg power was observed only in VC group at 30 and 360 days after the intervention. CONCLUSION: We conclude that rMV is a safe, short-lasting and non-invasive treatment that can significantly and persistently improve muscle performance and can effectively counteract progressive demineralisation in postmenopausal and osteoporotic women.

Prolonged asymmetric vestibular stimulation induces opposite, long-term effects on self-motion perception and ocular responses.

Self-motion perception and the vestibulo-ocular reflex (VOR) were investigated in healthy subjects during asymmetric whole body yaw plane oscillations while standing on a platform in the dark. Platform oscillation consisted of two half-sinusoidal cycles of the same amplitude (40°) but different duration, featuring a fast (FHC) and a slow half-cycle (SHC). Rotation consisted of four or 20 consecutive cycles to probe adaptation further with the longer duration protocol. Self-motion perception was estimated by subjects tracking with a pointer the remembered position of an earth-fixed visual target. VOR was measured by electro-oculography. The asymmetric stimulation pattern consistently induced a progressive increase of asymmetry in motion perception, whereby the gain of the tracking response gradually increased during FHCs and decreased during SHCs. The effect was observed already during the first few cycles and further increased during 20 cycles, leading to a totally distorted location of the initial straight-ahead. In contrast, after some initial interindividual variability, the gain of the slow phase VOR became symmetric, decreasing for FHCs and increasing for SHCs. These oppositely directed adaptive effects in motion perception and VOR persisted for nearly an hour. Control conditions using prolonged but symmetrical stimuli produced no adaptive effects on either motion perception or VOR. These findings show that prolonged asymmetric activation of the vestibular system leads to opposite patterns of adaptation of self-motion perception and VOR. The results provide strong evidence that semicircular canal inputs are processed centrally by independent mechanisms for perception of body motion and eye movement control. These divergent adaptation mechanisms enhance awareness of movement toward the faster body rotation, while improving the eye stabilizing properties of the VOR.

Focal vibration of quadriceps muscle enhances leg power and decreases knee joint laxity in female volleyball players.

AIM: This double-blind randomized controlled study aims at determining the effect of repeated muscle vibration (rMV) on explosive and reactive leg power and on knee laxity of female volleyball players. METHODS: Eighteen voluntary volleyball athletes, belonging to the same senior regional level team (age=22.7 ± 3 years, height=180.3 ± 5 cm, mass= 64 ± 4 kg) were assigned to three groups (N.=6) for vibration on contracted quadriceps (VC), vibration on relaxed muscle (VR), and sham vibration (NV), respectively. Intervention consisted in 3 rMV sessions performed in 3 consecutive days. In each session, 100 Hz, 300-500 µm amplitude vibratory stimuli were bilaterally delivered to the quadriceps in three consecutive 10-minutes applications. Explosive and reactive leg power and knee joint laxity were evaluated 1 day before, and 1, 30, and 240 days after intervention. RESULTS: In VC group, explosive and reactive leg power increased respectively by ~16% and ~9% at 1 day, by ~19% and ~11% at 30 days and by ~26% and ~13% at 240 days, concomitantly knee laxity decreased by ~6%, ~15% and ~18% at the same times. These changes were significantly larger than in the other groups, in which leg power increment and knee joint laxity reduction remained close to ~3%, ~5% and ~10% at 1, 30 and 240 days, respectively. CONCLUSION: Combined bilateral voluntary contraction and rMV of the quadriceps muscles is a short-lasting, non-invasive technique that can significantly and persistently improve muscle performance and knee laxity in volleyball women players.

Head position modulates optokinetic nystagmus.

Orientation and movement relies on both visual and vestibular information mapped in separate coordinate systems. Here, we examine how coordinate systems interact to guide eye movements of rabbits. We exposed rabbits to continuous horizontal optokinetic stimulation (HOKS) at 5°/s to evoke horizontal eye movements, while they were statically or dynamically roll-tilted about the longitudinal axis. During monocular or binocular HOKS, when the rabbit was roll-tilted 30° onto the side of the eye stimulated in the posterior â†’ anterior (P â†’ A) direction, slow phase eye velocity (SPEV) increased by 3.5-5°/s. When the rabbit was roll-tilted 30° onto the side of the eye stimulated in the A â†’ P direction, SPEV decreased to ~2.5°/s. We also tested the effect of roll-tilt after prolonged optokinetic stimulation had induced a negative optokinetic afternystagmus (OKAN II). In this condition, the SPEV occurred in the dark, "open loop." Modulation of SPEV of OKAN II depended on the direction of the nystagmus and was consistent with that observed during "closed loop" HOKS. Dynamic roll-tilt influenced SPEV evoked by HOKS in a similar way. The amplitude and the phase of SPEV depended on the frequency of vestibular oscillation and on HOKS velocity. We conclude that the change in the linear acceleration of the gravity vector with respect to the head during roll-tilt modulates the gain of SPEV depending on its direction. This modulation improves gaze stability at different image retinal slip velocities caused by head roll-tilt during centric or eccentric head movement.

Synaptic plasticity in the medial vestibular nuclei: role of glutamate receptors and retrograde messengers in rat brainstem slices.

The analysis of cellular-molecular events mediating synaptic plasticity within vestibular nuclei is an attempt to explain the mechanisms underlying vestibular plasticity phenomena. The present review is meant to illustrate the main results, obtained in vitro, on the mechanisms underlying long-term changes in synaptic strength within the medial vestibular nuclei. The synaptic plasticity phenomena taking place at the level of vestibular nuclei could be useful for adapting and consolidating the efficacy of vestibular neuron responsiveness to environmental requirements, as during visuo-vestibular recalibration and vestibular compensation. Following a general introduction on the most salient features of vestibular compensation and visuo-vestibular adaptation, which are two plastic events involving neuronal circuitry within the medial vestibular nuclei, the second and third sections describe the results from rat brainstem slice studies, demonstrating the possibility to induce long-term potentiation and depression in the medial vestibular nuclei, following high frequency stimulation of the primary vestibular afferents. In particular the mechanisms sustaining the induction and expression of vestibular long-term potentiation and depression, such as the role of various glutamate receptors and retrograde messengers have been described. The relevant role of the interaction between the platelet-activating factor, acting as a retrograde messenger, and the presynaptic metabotropic glutamate receptors, in determining the full expression of vestibular long-term potentiation is also underlined. In addition, the mechanisms involved in vestibular long-term potentiation have been compared with those leading to long-term potentiation in the hippocampus to emphasize the most significant differences emerging from vestibular studies. The fourth part, describes recent results demonstrating the essential role of nitric oxide, another retrograde messenger, in the induction of vestibular potentiation. Finally the fifth part suggests the possible functional significance of different action times of the two retrograde messengers and metabotropic glutamate receptors, which are involved in mediating the presynaptic mechanism sustaining vestibular long-term potentiation.

Contribution of self-motion perception to acoustic target localization.

CONCLUSION: The findings of this study suggest that acoustic spatial perception during head movement is achieved by the vestibular system, which is responsible for the correct dynamic of acoustic target pursuit. OBJECTIVE: The ability to localize sounds in space during whole-body rotation relies on the auditory localization system, which recognizes the position of sound in a head-related frame, and on the sensory systems, namely the vestibular system, which perceive head and body movement. The aim of this study was to analyse the contribution of head motion cues to the spatial representation of acoustic targets in humans. MATERIAL AND METHODS: Healthy subjects standing on a rotating platform in the dark were asked to pursue with a laser pointer an acoustic target which was horizontally rotated while the body was kept stationary or maintained stationary while the whole body was rotated. The contribution of head motion to the spatial acoustic representation could be inferred by comparing the gains and phases of the pursuit in the two experimental conditions when the frequency was varied. RESULTS: During acoustic target rotation there was a reduction in the gain and an increase in the phase lag, while during whole-body rotations the gain tended to increase and the phase remained constant. The different contributions of the vestibular and acoustic systems were confirmed by analysing the acoustic pursuit during asymmetric body rotation. In this particular condition, in which self-motion perception gradually diminished, an increasing delay in target pursuit was observed.

Vestibulo-ocular reflexes in rabbits: reduction by intravenous injection of diazepam.

We have studied the influence of intravenously administered diazepam on the horizontal (HVOR) and vertical (VVOR) vestibulo-ocular reflexes of the rabbit. The HVOR and VVOR were evoked by sinusoidal oscillation of rabbits on a rate table (0.01 to 0.8 Hz, +/- 10 degrees), and eye movements were measured with an infrared light-projection technique. The gains of the HVOR and VVOR (evoked eye velocity/head velocity) were reduced by diazepam injections of 5 microgram/kg. The dose required to produce a 50% reduction in HVOR gain was 500 microgram/kg. The time required to reduce the HVOR gain to 50% of its maximal reduction at dose of 400 microgram/kg (0.4 Hz +/- 10 degrees) was 60 s. These data suggest that diazepam might be effective as an anti-motion-sickness agent.

Role of nitric oxide in long-term potentiation of the rat medial vestibular nuclei.

In rat brainstem slices, we investigated the role of nitric oxide in long-term potentiation induced in the ventral portion of the medial vestibular nuclei by high-frequency stimulation of the primary vestibular afferents. The nitric oxide scavenger [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide ] and the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester were administered before and after induction of potentiation. Both drugs completely prevented long-term potentiation, whereas they did not impede the potentiation build-up, or affect the already established potentiation. These results demonstrate that the induction, but not the maintenance of vestibular long-term potentiation, depends on the synthesis and release into the extracellular medium of nitric oxide. In addition, we analysed the effect of the nitric oxide donor sodium nitroprusside on vestibular responses. Sodium nitroprusside induced long-term potentiation, as evidenced through the field potential enhancement and unit peak latency decrease. This potentiation was impeded by D, L-2-amino-5-phosphonopentanoic acid, and was reduced under blockade of synaptosomal platelet-activating factor receptors by ginkgolide B and group I metabotropic glutamate receptors by (R,S)-1-aminoindan-1, 5-dicarboxylic acid. When reduced, potentiation fully developed following the washout of antagonist, demonstrating an involvement of platelet-activating factor and group I metabotropic glutamate receptors in its full development. Potentiation induced by sodium nitroprusside was also associated with a decrease in the paired-pulse facilitation ratio, which persisted under ginkgolide B, indicating that nitric oxide increases glutamate release independently of platelet-activating factor-mediated presynaptic events. We suggest that nitric oxide, released after the activation of N-methyl-D-aspartate receptors, acts as a retrograde messenger leading to an enhancement of glutamate release to a sufficient level for triggering potentiation. Once the synaptic efficacy has changed, it becomes a long-lasting phenomenon only through a subsequent action of platelet-activating factor.

Effects of metabotropic glutamate receptor block on the synaptic transmission and plasticity in the rat medial vestibular nuclei.

In rat brainstem slices, we investigated the possible role of metabotropic glutamate receptors in modulating the synaptic transmission within the medial vestibular nuclei, under basal and plasticity inducing conditions. We analysed the effect of the metabotropic glutamate receptor antagonist (R,S)-alpha-methyl-4-carboxyphenylglycine on the amplitude of the field potentials and latency of unitary potentials evoked in the ventral portion of the medial vestibular nuclei by primary vestibular afferent stimulation, and on the induction and maintenance of long-term potentiation, after high-frequency stimulation. Two effects were observed, consisting of a slight increase of the field potentials and reduction of unit latency during the drug infusion, and a further long-lasting development of these modifications after the drug wash-out. The long-term effect depended on N-methyl-D-aspartate receptor activation, as D,L-2-amino-5-phosphonopentanoic acid prevented its development. We suggest that (R,S)-alpha-methyl-4carboxyphenylglycine enhances the vestibular responses and induces N-methyl-D-aspartate-dependent long-term potentiation by increasing glutamate release, through the block of presynaptic metabotropic glutamate receptors which actively inhibit it. The block of these receptors was indirectly supported by the fact that the agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid reduced the vestibular responses and blocked the induction of long-term potentiation by high-frequency stimulation. The simultaneous block of metabotropic glutamate receptors facilitating synaptic plasticity, impedes the full expression of the long-term effect throughout the (R,S)-alpha-methyl-4-carboxyphenylglycine infusion. The involvement of such a facilitatory mechanism in the potentiation is supported by its reversible reduction following a second (R,S)-alpha-methyl-4-carboxyphenylglycine infusion. The drug also reduced the expression of potentiation induced by high-frequency stimulation. Conversely the electrical long-term potentiation was still induced, but it was occluded by the previous drug potentiation. We conclude that metabotropic glutamate receptors play a dual functional role in the medial vestibular nuclei, consisting in the inhibition of glutamate release under basal conditions, and the facilitation of N-methyl-D-aspartate-dependent plasticity phenomena.

Platelet-activating factor and group I metabotropic glutamate receptors interact for full development and maintenance of long-term potentiation in the rat medial vestibular nuclei.

In rat brainstem slices, we investigated the interaction between platelet-activating factor and group I metabotropic glutamate receptors in mediating long-term potentiation within the medial vestibular nuclei. We analysed the N1 field potential wave evoked in the ventral portion of the medial vestibular nuclei by primary vestibular afferent stimulation. The group I metabotropic glutamate receptor antagonist, (R,S)-1-aminoindan-1,5-dicarboxylic acid, prevented long-term potentiation induced by a platelet-activating factor analogue [1-O-hexadecyl-2-O-(methylcarbamyl)-sn-glycero-3-phosphocholine], as well as the full development of potentiation, induced by high-frequency stimulation under the blocking agent for synaptosomal platelet-activating factor receptors (ginkolide B), at drug washout. However, potentiation directly induced by the group I glutamate metabotropic receptor agonist, (R,S)-3,5-dihydroxyphenylglycine, was reduced by ginkolide B. These findings suggest that platelet-activating factor, whether exogenous or released following potentiation induction, exerts its effect through presynaptic group I metabotropic glutamate receptors, mediating the increase of glutamate release. In addition, we found that this mechanism, which led to full potentiation through presynaptic group I metabotropic glutamate receptor activation, was inactivated soon after application of potentiation-inducing stimulus. In fact, the long-lasting block of the platelet-activating factor and metabotropic glutamate receptors prevented the full potentiation development and the induced potentiation progressively declined to null. Moreover, ginkolide B, given when high-frequency-dependent potentiation was established, only reduced it within 5 min after potentiation induction. We conclude that to fully develop vestibular long-term potentiation requires presynaptic events. Platelet-activating factor, released after the activation of postsynaptic mechanisms which induce potentiation, is necessary for coupling postsynaptic and presynaptic phenomena, through the activation of group I metabotropic glutamate receptors, and its action lasts only for a short period. If this coupling does not occur, a full and long-lasting potentiation cannot develop.

Exogenous glutamate induces short and long-term potentiation in the rat medial vestibular nuclei.

In rat brain stem slices, high concentrations of exogenous glutamate induce long-term potentiation (LTP) of the field potentials evoked in the medial vestibular nuclei (MVN) by vestibular afferent stimulation. At low concentrations, glutamate can also induce short-term potentiation (STP), indicating that LTP and STP are separate events depending on the level of glutamatergic synapse activation. LTP and STP are prevented by blocking NMDA receptors and nitric oxide (NO) synthesis. Conversely, blocking platelet-activating factor (PAF) and group I metabotropic glutamate receptors only prevents the full development of LTP. Moreover, in the presence of blocking agents, glutamate causes transient inhibition, suggesting that when potentiation is impeded, exogenous glutamate can activate presynaptic mechanisms that reduce glutamate release.

Tonic cervical influences on eye nystagmus following hemilabyrinthectomy: immediate and plastic effects.

In intact guinea pigs a passive horizontal rotation of the body about the fixed head induces compensatory ocular movements (cervico-ocular reflex). When the static neck deviation is maintained, a significant ocular displacement is observed. In acutely hemilabyrinthectomized animals, static body deviation towards the lesion side tonically alters eye nystagmus. It affects slow phase eye velocity and quick phase amplitude and frequency causing the eye to reach a less eccentric orbital position. Apart from such immediate influences, a plastic effect on eye nystagmus abatement is induced. In the animals restrained with no body-on-head deviation, abatement of nystagmus is delayed with respect to the animals restrained with 35 degrees body deviation towards the lesion side. Thus the head position signal is not only a contributing factor for the correction of postural deficits but also influences the time course of the ocular balancing process following unilateral vestibular damage.

Vestibular contribution to the orientation of cervico-ocular reflex in rabbit.

In the rabbit the cervico-ocular reflex (COR) helps to maintain the gaze stability during passive head displacements, by increasing the gain and decreasing the phase lead of low frequency vestibular responses and by diminishing in amplitude the anticompensatory vestibular fast phases. These cervical influences appear only for horizontal stimulations, while they are scarce or absent in the vertical and sagittal planes. Ocular responses to horizontal body displacements are oriented in the horizontal plane and remain in the same plane when the head is statically pitched at various degrees, in spite of the directional changes in the extraocular muscle (EOM) lines of force with respect to space. Tension recordings from the EOMs show that the oculomotor system is differently activated depending upon the degree of head inclination. This change in the EOM activation is not observed when the body, instead of the head, is pitched. Furthermore, after bilateral labyrinthectomy (BL) the cervico-ocular responses lose their appropriate directionality. It is concluded that the information for determining the plane of the eye movements during cervical stimulations does not originate from the neck proprioception but is provided by the otolithic receptors.

The horizontal and vertical cervico-ocular reflexes of the rabbit.

Horizontal and vertical cervico-ocular reflexes of the rabbit (HCOR, VCOR) were evoked by sinusoidal oscillation of the body about the vertical and longitudinal axes while the head was fixed. These reflexes were studied over a frequency range of 0.005-0.800 Hz and at stimulus amplitudes of +/- 10 degrees. When the body of the rabbit was rotated horizontally clockwise around the fixed head, clockwise conjugate eye movements were evoked. When the body was rotated about the longitudinal axis onto the right side, the right eye rotated down and the left eye rotated up. The mean gain of the HCOR (eye velocity/body velocity) rose from 0.21 and 0.005 Hz to 0.27 at 0.020 Hz and then declined to 0.06 at 0.3Hz. The gain of the VCOR was less than the gain of the HCOR by a factor of 2-3. The HCOR was measured separately and in combination with the horizontal vestibulo-ocular reflex (HVOR). These reflexes combine linearly. The relative movements of the first 3 cervical vertebrae during stimulation of the HCOR and VCOR were measured. For the HCOR, the largest angular displacement (74%) occurs between C1 and C2. For the VCOR, the largest relative angular displacement (45%) occurs between C2 and C3. Step horizontal clockwise rotation of the head and body (HVOR) evoked low velocity counterclockwise eye movements followed by fast clockwise (resetting) eye movements. Step horizontal clockwise rotation of the body about the fixed head (HCOR) evoked low velocity clockwise eye movements which were followed by fast clockwise eye movements. Step horizontal clockwise rotation of the head about the fixed body (HCOR + HVOR) evoked low velocity counterclockwise eye movements which were not interrupted by fast clockwise eye movements. These data provide further evidence for a linear combination of independent HCOR and HVOR signals.

The role of GABA in NMDA-dependent long term depression (LTD) of rat medial vestibular nuclei.

The role of GABA in NMDA-dependent long term depression (LTD) in the medial vestibular nuclei (MVN) was studied on rat brainstem slices. High frequency stimulation (HFS) of the primary vestibular afferents induces a long lasting reduction of the polysynaptic (N2) component of the field potentials recorded in the dorsal portion of the MVN. The induction but not the maintenance of this depression was abolished by AP5, a specific blocking agent for glutamate NMDA receptors. The involvement of GABA in mediating the depression was checked by applying the GABAA and GABAB receptor antagonists, bicuculline and saclofen, before and after HFS. Under bicuculline and saclofen perfusion, HFS provoked a slight potentiation of the N2 wave, while the N2 depression clearly emerged after drug wash-out. This indicates that GABA is not involved in inducing the long term effect, but it is necessary for its expression. Similarly, the LTD reversed and a slight potentiation appeared when both drugs were administered after its induction. Most of these effects were due to the bicuculline, suggesting that GABAA receptors contribute to LTD more than GABAB do. According to our results, it is unlikely that the long lasting vestibular depression is the result of a homosynaptic LTD. On the contrary, our findings suggest that the depression is due to an enhancement of the GABA inhibitory effect, caused by an HFS dependent increase in gabaergic interneuron activity, which resets vestibular neuron excitability at a lower level.

Central projections and entries of capsaicin-sensitive muscle afferents.

The entry pathway and central distribution of A delta and C muscle afferents within the central nervous system (CNS) were investigated by combining electron microscopy and electrophysiological analysis after intramuscular injection of capsaicin. The drug was injected into the rat lateral gastrocnemius (LG) and extraocular (EO) muscles. The compound action potentials of LG nerve and the evoked field potentials recorded in semilunar ganglion showed an immediate and permanent reduction in A delta and C components. The morphological data revealed degenerating unmyelinated axons and terminals in the inner sublamina II and in the border of laminae I-II of the dorsal horn at L4-L5 and C1-C2 (subnucleus caudalis trigemini) spinal cord segments. Most degenerating terminals were the central bouton (C) of type I and II synaptic glomeruli. Furthermore, degenerating peripheral axonal endings (V2) presynaptic to normal C were found. Since V2 were previously found degenerated after cutting the oculomotor nerve (ON) or L4 ventral root, we conclude that some A delta and C afferents from LG and EO muscles entering the CNS by ON or ventral roots make axoaxonic synapses on other primary afferents to promote an afferent control of sensory input.

Peripheral territory and neuropeptides of the trigeminal ganglion neurons centrally projecting through the oculomotor nerve demonstrated by fluorescent retrograde double-labeling combined with immunocytochemistry.

The peripheral territories of sheep trigeminal neurons which send their central process to the brainstem through the oculomotor nerve were investigated by the use of fluorescent tracers in double-labeling experiments. For this purpose Diamidino yellow (DY) injection into the oculomotor nerve was combined with Fast blue (FB) injection either into the extraocular muscles (EOMs), or the cornea, or the superior eyelid. Double-labeled DY + FB cells were found in the ophthalmic region of the trigeminal ganglion in addition to single-labeled DY or FB cells. The DY and DY + FB-labeled trigeminal cells were analysed immunocytochemically for their content of substance P (SP)-, calcitonin gene-related peptide (CGRP)-, and cholecystokinin-8 (CCK-8)-like. All single-labeled DY cells showed SP-, CGRP- or CCK-8-like immunoreactivity. Double-labeled DY + FB neurons innervating the EOMs were immunoreactive for each of the three peptides, whereas double-labeled neurons supplying the cornea were only CGRP-like positive. The findings suggest that, in the sheep, trigeminal neurons which send their process centrally through the oculomotor nerve supply the EOMs, the cornea, and the superior eyelid and contain neuropeptides which are usually associated with pain sensation.