Biomedical subjects

V E Pettorossi

Publications and source records attributed to V E Pettorossi.

At least 19 recordsLinked to original sources

PubMed2006

Improvement of posture stability by vibratory stimulation following anterior cruciate ligament reconstruction.

Surgical reconstruction of the anterior cruciate ligament (ACL) may reduce, but it does not always eliminate, knee and body instability because of a persisting proprioceptive deficit. In order to enhance body stability, a new protocol of treatment has been proposed consisting of mechanical vibration (100 Hz frequency and < 20 microm amplitude) of the quadriceps muscle in the leg that has undergone ACL reconstruction. In our trials, stimulation was performed when the quadriceps muscle was kept isometrically contracted. Treatment was started one month after surgery. Vibration was applied for short periods over three consecutive days. Nine months after treatment, postural stability was re-evaluated with the subjects standing on one leg with open and with closed eyes. The postural stability of the subjects having undergone vibration treatment, standing on the operated leg was significantly improved one day after treatment when evaluated as mean of speed and elliptic area of the center of pressure. The improvement persisted and increased during the following weeks. Peak torques of the operated leg extensor muscles also increased and reached values close to that of the leg, which had not been operated. Conversely, the balance of the untreated subjects standing on the operated leg did not improve and the restoration of the extensor muscle peak torque was poor. It is concluded that short lasting proprioceptive activation by vibration may lead to a faster and more complete equilibrium recovery probably by permanently changing the network controlling knee posture.

Adult↗

PubMed2005

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.

Acoustics↗

PubMed2004

Contribution of eye position to movement perception.

OBJECTIVE: To investigate the influence of gaze eccentricity on movement perception during asymmetric vestibular stimulation. MATERIAL AND METHODS: Subjects (n = 10) were placed on a rotating platform and oscillated asymmetrically in the dark. Subjects were asked to reproduce with a pointer the location in space of a light spot that was turned off at the beginning of the oscillation. The target was presented in centric and eccentric (0 degrees, 20 degrees and 40 degrees) positions. RESULTS: In the centric position a large shift from the real position of the target was observed in the opposite direction to that of the faster vestibular stimulation. The shift increased when the target was placed eccentrically toward the slower vestibular stimulation side and decreased when it was placed in the opposite direction. CONCLUSION: The dependence of rotation perception on the target position suggests that the eye deviation, imposed by the eccentricity of the target, is able to influence the perception of body movement and may modulate the internal reference frame.

Adult↗

PubMed2002

Eye position signals modify vestibulo- and cervico-ocular fast phases during passive yaw rotations in humans.

We studied the amplitude, latency, and probability of occurrence of fast phases (FP) in darkness to unpredictable vestibular and/or cervical yaw stimulation in normal human subjects. The rotational stimuli were smoothed trapezoidal motion transients of 14 degrees amplitude and 1.25 s duration. Eye position before stimulus application (initial eye position, IEP) was introduced as a variable by asking the subjects to fixate a spot appearing either straight ahead or at 7 degrees eccentric positions. The recordings demonstrated that the generation of FP during vestibular stimulation was facilitated when the whole-body rotation was directed opposite the eccentric IEP. Conversely, FP were attenuated if the whole-body rotation was directed toward the eccentric IEP; i.e., the FP attenuated if they were made to further eccentric positions. Cervical stimulation-induced FP were small and variable in direction when IEP was directed straight ahead before stimulus onset. Eccentric IEPs resulted in large FP, the direction of which was essentially independent of the neck-proprioceptive stimulus. They tended to move the eye toward the primary position, both when the trunk motion under the stationary head was directed toward or away from the IEP. FP dependence on IEP was evident also during head-on-trunk rotations. No consistent interaction between vestibularly and cervically induced FP was found. We conclude that extraretinal eye position signals are able to modify vestibularly evoked reflexive FP in darkness, aiming at minimizing excursions of the eyes away from the primary position. However, neck-induced FP do not relate to specific tasks of stabilization or visual search. By keeping the eyes near the primary position, FP may permit flexibility of orienting responses to incoming stimuli. This recentering bias for both vestibularly and cervically generated FP may represent a visuomotor optimizing strategy.

Adult↗

PubMed2002

Cerebellar nodulectomy impairs spatial memory of vestibular and optokinetic stimulation in rabbits.

Natural vestibular and optokinetic stimulation were used to investigate the possible role of the cerebellar nodulus in the regulation and modification of reflexive eye movements in rabbits. The nodulus and folium 9d of the uvula were destroyed by surgical aspiration. Before and after nodulectomy the vertical and horizontal vestibuloocular reflexes (VVOR, HVOR) were measured during sinusoidal vestibular stimulation about the longitudinal (roll) and vertical (yaw) axes. Although the gain of the HVOR (G(HVOR) = peak eye movement velocity/peak head velocity) was not affected by the nodulectomy, the gain of the VVOR (G(VVOR)) was reduced. The gains of the vertical and horizontal optokinetic reflexes (G(VOKR), G(HOKR)) were measured during monocular, sinusoidal optokinetic stimulation (OKS) about the longitudinal and vertical axes. Following nodulectomy, there was no reduction in G(VOKR) or G(HOKR). Long-term binocular OKS was used to generate optokinetic afternystagmus, OKAN II, that lasts for hours. After OKAN II was induced, rabbits were subjected to static pitch and roll, to determine how the plane and velocity of OKAN II is influenced by a changing vestibular environment. During static pitch, OKAN II slow phase remained aligned with earth-horizontal. This was true for normal and nodulectomized rabbits. During static roll, OKAN II remained aligned with earth-horizontal in normal rabbits. During static roll in nodulectomized rabbits, OKAN II slow phase developed a centripetal vertical drift. We examined the suppression and recovery of G(VVOR) following exposure to conflicting vertical OKS for 10-30 min. This vestibular-optokinetic conflict reduced G(VVOR) in both normal and nodulectomized rabbits. The time course of recovery of G(VVOR) after conflicting OKS was the same before and after nodulectomy. In normal rabbits, the head pitch angle, at which peak OKAN II velocity occurred, corresponded to the head pitch angle maintained during long-term OKS. If the head was maintained in a "pitched-up" or "pitched-down" orientation during long-term OKS, the subsequently measured OKAN II peak velocity occurred at the same orientation. This was not true for nodulectomized rabbits, who had OKAN II peak velocities at head pitch angles independent of those maintained during long-term OKS. We conclude that the nodulus participates in the regulation of compensatory reflexive movements. The nodulus also influences "remembered" head position in space derived from previous optokinetic and vestibular stimulation.

Animals↗

PubMed2002

Capsaicin-sensitive muscle afferents modulate the monosynaptic reflex in response to muscle ischemia and fatigue in the rat.

The role of muscle ischemia and fatigue in modulating the monosynaptic reflex was investigated in decerebrate and spinalized rats. Field potentials and fast motoneuron single units in the lateral gastrocnemious (LG) motor pool were evoked by dorsal root stimulation. Muscle ischemia was induced by occluding the LG vascular supply and muscle fatigue by prolonged tetanic electrical stimulation of the LG motor nerve. Under muscle ischemia the monosynaptic reflex was facilitated since the size of the early and late waves of the field potential and the excitability of the motoneuron units increased. This effect was abolished after L3-L6 dorsal rhizotomy, but it was unaffected after L3-L6 ventral rhizotomy. By contrast, the monosynaptic reflex was inhibited by muscle fatiguing stimulation, and this effect did not fully depend on the integrity of the dorsal root. However, when ischemia was combined with repetitive tetanic muscle stimulation the inhibitory effect of fatigue was significantly enhanced. Both the ischemia and fatigue effects were abolished by capsaicin injected into the LG muscle at a dose that blocked a large number of group III and IV muscle afferents. We concluded that muscle ischemia and fatigue activate different groups of muscle afferents that are both sensitive to capsaicin, but enter the spinal cord through different roots. They are responsible for opposite effects, when given separately: facilitation during ischemia and inhibition during fatigue; however, in combination, ischemia enhances the responsiveness of the afferent fibres to fatigue.

Animals↗

PubMed2001

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.

2-Amino-5-phosphonovalerate↗

PubMed2001

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.

Afferent Pathways↗

PubMed2001

Proprioceptive influence on the optokinetic nystagmus.

The influence of neck and leg proprioceptive inputs on optokinetic-induced quick phases was studied in humans. Ten subjects received unidirectional horizontal optokinetic stimulation (10-20%/s) during sinusoidal neck, leg and combined neck + leg proprioceptive stimulation. The optokinetic reflex was measured by electro-oculography. Neck stimulation induced a shift in the nystagmus beating field in the opposite direction to body movement (gain 0.3 0.4, phase 140-180 degrees). The beating field shift resulted totally from the amplitude and frequency modulation of optokinetic quick phases, as slow phases were not affected. Leg proprioceptive stimulation induced a similar effect, but the phase of the response lagged by approximately 90 degrees compared with that of neck response. With combined neck + leg stimulation, the amplitude of the effect was a sum of the separate effects, but the phase coincided with that of the leg response. This suggests that neck and leg proprioceptive signals do not add linearly and that the leg signal determines the time of the response.

Adult↗

PubMed2001

Role of cerebellar nodulus and uvula on the vestibular quick phase spatial constancy.

We investigated the orientation of quick phases (QPs) of vestibularly-induced eye movements in rabbits in response to "off-vertical" sinusoidal vestibular stimulation. We also examined the possible role of the cerebellar nodulus and ventral uvula in controlling QP spatial orientation and modification. During "off-vertical" vestibular stimulation QPs remained aligned with the earth's horizontal plane, while the slow phases (SPs) were aligned with the plane of vestibular stimulation. This suggests that QPs are coded in gravito-inertial coordinates and SPs in head coordinates. When rabbits were oscillated in the light (20 degrees peak-to-peak; 0.2 Hz) about an "off-vertical" axis for 2 h, the QPs changed their trajectory, abandoning the earth's horizontal plane to approach the plane of the stimulus. By contrast, in the absence of conjunctive optokinetic stimulation, QPs remained fixed in the earth's horizontal plane even after 2 h of "off-vertical" stimulation. The conjunctive combination of optokinetic and vestibular stimulation caused QPs to change their plane of rotation. After lesion of the nodulus-uvula the ability of rabbits to reorient QPs during conjoint vestibular-optokinetic stimulation was maintained. We conclude that the space orientation and adaptation of QPs do not require cerebellar control.

Adaptation, Physiological↗

PubMed2001

Different contributions of platelet-activating factor and nitric oxide in long-term potentiation of the rat medial vestibular nuclei.

In rat brainstem slices, we investigated the differential role of nitric oxide (NO) and platelet-activating factor (PAF) in long-term potentiation (LTP) induced in the ventral portion of the medial vestibular nuclei (MVN) by high-frequency stimulation (HFS) of the primary vestibular afferents. The NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO) and the PAF receptor antagonist ginkgolide B (BN-52021) were administered before and after induction of potentiation. The effect of carboxy-PTIO was to completely prevent LTP. By contrast, BN-52021 only reduced the amplitude of HFS potentiation, which could develop fully at the drug washout or decline to zero, becoming a short-term phenomenon, in the case of long-lasting PAF receptor block. Both drugs, when given after HFS, had no effect on the already established potentiation, but whilst BN-52021 showed an influence within 5 min of the LTP induction, carboxy-PTIO did not affect the response once HFS was delivered. Moreover, we showed that the NO donor, sodium nitroprusside, and methylcarbamyl PAF (mc-PAF) induced LTP which was associated with an increase in glutamate release as shown by reduction in the paired-pulse facilitation ratio. The mc-PAF LTP was prevented by the NO scavenger, while NO LTP was only reduced by BN-52021. We suggest that NO and PAF are implicated as retrograde messengers in two different phases of vestibular LTP: NO in the induction phase; and PAF in the full expression phase.

Animals↗

PubMed2000

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.

Action Potentials↗

PubMed2000

Influence of gravity on the spatial orientation of eye nystagmus induced by unilateral lesion of horizontal semicircular canal.

The influence of gravity in the orientation and slow phase eye velocity of the ocular nystagmus following unilateral damage of the cupula in the ampulla of the horizontal semicircular canal (UHCD) was investigated. The nystagmus was analysed at different sagittal head positions using the x-y infrared eye monitor technique. The nystagmus was almost horizontal at 0 degrees head pitch angle and remained partially fixed in space when the head was pitched upward or downward. The reorientation gain of the slow and quick phases was high (about 0.75) within +/- 45 degrees of head pitch angle, but beyond this range, it decreased greatly. The gain value depended on the lesion extension to otolithic receptors. The absolute value of the slow phase eye velocity of UHCD nystagmus was also modified systematically by the head pitch, showing a reduction in the upward and an increase in the downward.

Animals↗

PubMed1999

The role of capsaicin-sensitive muscle afferents in fatigue-induced modulation of the monosynaptic reflex in the rat.

1. The role of group III and IV afferent fibres of the lateral gastrocnemious muscle (LG) in modulating the homonymous monosynaptic reflex was investigated during muscle fatigue in spinalized rats. 2. Muscle fatigue was induced by a series of increasing tetanic electrical stimuli (85 Hz, 600 ms) delivered to the LG muscle nerve. Series consisted of increasing train numbers from 1 to 60. 3. Potentials from the spinal cord LG motor pool and from the ventral root were recorded in response to proprioceptive afferent stimulation and analysed before and during tetanic muscle activations. Both the pre- and postsynaptic waves showed an initial enhancement and, after a '12-train' series, an increasing inhibition. 4. The enhancement of the responses to muscle fatiguing stimulation disappeared after L3-L6 dorsal root section, while a partial reflex inhibition was still present. Conversely, after section of the corresponding ventral root, there was only a reduction in the inhibitory effect. 5. The monosynaptic reflex was also studied in animals in which a large number of group III and IV muscle afferents were eliminated by injecting capsaicin (10 mM) into the LG muscle. As a result of capsaicin treatment, the fatigue-induced inhibition of the pre- and postsynaptic waves disappeared, while the response enhancement remained. 6. We concluded that the monosynaptic reflex inhibition, but not the enhancement, was mediated by those group III and IV muscle afferents that are sensitive to the toxic action of capsaicin. The afferents that are responsible for the response enhancement enter the spinal cord through the dorsal root, while those responsible for the inhibition enter the spinal cord through both the ventral and dorsal roots.

Animals↗

PubMed1999

Optokinetic and vestibular stimulation determines the spatial orientation of negative optokinetic afternystagmus in the rabbit.

Prolonged binocular optokinetic stimulation (OKS) in the rabbit induces a high-velocity negative optokinetic afternystagmus (OKAN II) that persists for several hours. We have taken advantage of this uniform nystagmus to study how changes in static head orientation in the pitch plane might influence the orientation of the nystagmus. After horizontal OKS, the rotation axis of the OKAN II remained almost constant in space as it was kept aligned with the gravity vector when the head was pitched by as much as 80 degrees up and 35 degrees down. Moreover, during reorientation, slow-phase eye velocity decreased according to the head pitch angle. Thereafter, we analyzed the space orientation of OKAN II after optokinetic stimulation during which the head and/or the OKS were pitched upward and downward. The rotation axis of OKAN II did not remain aligned with an earth vertical axis nor a head vertical axis, but it tended to be aligned with that of the OKS respace. The slow-phase eye velocity of OKAN II was also affected by the head pitch angle during OKS, because maximal OKAN II velocity occurred at the same head pitch angle as that during optokinetic stimulation. We suggest that OKAN II is coded in gravity-centered rather than in head-centered coordinates, but that this coordinate system may be influenced by optokinetic and vestibular stimulation. Moreover, the velocity attenuation of OKAN II seems to depend on the mismatch between the space-centered nystagmus rotation axis orientation and that of the "remembered" head-centered optokinetic pathway activated by OKS.

Animals↗

PubMed1999

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.

Afferent Pathways↗

PubMed1998

Assessment of the perception of verticality and horizontality with self-paced saccades.

We investigated the ability of human subjects (Ss) to make self-paced saccades in the earth-vertical and horizontal directions (space-referenced task) and in the direction of the head-vertical and horizontal axis (self-referenced task) during whole body tilts of 0 degrees, 22.5 degrees, 45 degrees and 90 degrees in the frontal (roll) plane. Saccades were recorded in the dark with computerised video-oculography. During space-referenced tasks, the saccade vectors did not fully counter-rotate to compensate for larger angles of body tilt. This finding is in agreement with the 'A' effect reported for the visual vertical. The error was significantly larger for saccades intended to be space-horizontal than space-vertical. This vertico-horizontal dissociation implies greater difficulty in defining horizontality than verticality with the non-visual motor task employed. In contrast, normal Ss (and an alabyrinthine subject tested) were accurate in orienting saccades to their own (cranio-centric) vertical and horizontal axes regardless of tilt indicating that cranio-centric perception is robust and apparently not affected by gravitational influences.

Adult↗

PubMed1998

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.

Animals↗