Plastic changes induced by muscle focal vibration: A possible mechanism for long-term motor improvements.

Repetitive focal vibrations can induce positive and persistent after-effects. There is still no satisfactory interpretation of the underlying mechanisms. A rationale, which can provide consistency among different results, is highly desirable to guide both the use of the application and future research. To date, interpretive models are formulated to justify the results, depending on the specific protocol adopted. Indeed, protocol parameters, such as stimulus intensity and frequency, intervention time and administration period, are variable among different studies. However, in this article, we have identified features of the protocols that may allow us to suggest a possible common mechanism underlying the effectiveness of focal vibration under different physiologic and pathologic conditions. Since repetitive focal muscle vibration induces powerful and prolonged activation of muscle proprioceptors, we hypothesize that this intense activation generates adaptive synaptic changes along sensory and motor circuits. This may lead to long-term synaptic potentiation in the central network, inducing an enhancement of the learning capability. The plastic event could increase proprioceptive discriminative ability and accuracy of the spatial reference frame and, consequently, improve motor planning and execution for different motor functions and in the presence of different motor dysfunctions. The proposed mechanism may explain the surprising and sometimes particularly rapid improvements in motor execution in healthy and diseased individuals, regardless of specific physical training. This hypothetic mechanism may require experimental evidence and could lead to extend and adapt the application of the "learning without training" paradigms to other functional and recovery needs.

Electroencephalographic response to transient adaptation of vestibular perception.

When given a series of sinusoidal oscillations in which the two hemicycles have equal amplitude but asymmetric velocity, healthy subjects lose perception of the slower hemicycle (SHC), reporting a drift towards the faster hemicycle (FHC). This response is not reflected in the vestibular-ocular reflex, suggesting that the adaptation is of higher order. This study aimed to define EEG correlates of this adaptive response. Twenty-five subjects underwent a series of symmetric or asymmetric oscillations and reported their perceived head orientation at the end using landmarks in the testing room; this was converted into total position error (TPE). Thirty-two channel EEG was recorded before, during and after adaptation. Spectral power and coherence were calculated for the alpha, beta, delta and theta frequency bands. Linear mixed models were used to determine a region-by-condition effect of the adaptation. TPE was significantly greater in the asymmetric condition and reported error was always in the direction of the FHC. Regardless of condition, alpha desynchronised in response to stimulation, then rebounded back toward baseline values. This pattern was accelerated and attenuated in the prefrontal and occipital regions, respectively, in the asymmetric condition. Functional connectivity networks were identified in the beta and delta frequency bands; these networks, primarily comprising frontoparietal connections, were more coherent during asymmetric stimulation. These findings suggest that the temporary vestibulo-perceptual 'neglect' induced by asymmetric vestibular stimulation may be mediated by alpha rhythms and frontoparietal attentional networks. The results presented further our understanding of brain rhythms and cortical networks involved in vestibular perception and adaptation. KEY POINTS: Whole-body asymmetric sinusoidal oscillations, which consist of hemicycles with equal amplitude but differing velocities, can induce transient 'neglect' of the slower hemicycle in the vestibular perception of healthy subjects. In this study, we aimed to elucidate EEG correlates of this 'neglect', thereby identifying a cortical role in vestibular perception and adaptation. We identified a desynchronisation-resynchronisation response in the alpha frequency band (8-14 Hz) that was accelerated in the prefrontal region and attenuated in the occipital region when exposed to asymmetric, as compared to symmetric, rotations. We additionally identified functional connectivity networks in the beta (14-30 Hz) and delta (1-4 Hz) frequency bands consisting primarily of frontoparietal connections. These results suggest a prominent role of alpha rhythms and frontoparietal attentional networks in vestibular perception and adaptation.

Inhibition of androgenic pathway impairs encoding of cerebellar-dependent motor learning in male rats.

Cerebellar-dependent learning is essential for the adaptation of motor and no motor behaviors to changing contexts, and neuroactive steroids-mainly referred to as estrogens-may regulate this process. However, the role of androgens in this process has not been established, although they may affect cerebellar physiology. Thus, this study aims to determine whether the activation of androgenic neural pathways may take part in controlling the vestibuloocular (VOR) and optokinetic reflexes (OKR), which depend on a defined cerebellar circuitry. To answer this question, we acutely blocked the activation of androgen receptors (Ars) using systemic administration of the Ars antagonist flutamide (FLUT; 20 mg/Kg) in peripubertal male rats. Then, we evaluated the FLUT effect on general oculomotor performance in the VOR and OKR as well as VOR adaptive gain increases and decreases. We used a paradigm causing fast VOR adaptation that combined in phase/out phase visuo-vestibular stimulations. We found that FLUT impaired the gain increase and decrease in VOR adaptation. However, FLUT altered neither acute nor overtime basal ocular-motor performance in the VOR or OKR. These findings indicate that the activation of androgenic neural pathways participates in phenomena leading to fast VOR adaptation, probably through the modulation of plasticity mechanisms that underlie adaptation of this reflex. Conversely, androgens may not be essential for neural information processing demands in basal ocular-motor reflexes. Moreover, our results suggest that androgens, possibly testosterone and dihydrotestosterone, could rapidly regulate motor memory encoding in the VOR adaptation, acting at both cerebellar and extracerebellar plasticity sites.

Is the Focal Muscle Vibration an Effective Motor Conditioning Intervention? A Systematic Review.

Mechanical vibration, applied to single or few muscles, can be a selective stimulus for muscle spindles, able to modify neuromuscular management, inducing short and long-term effects, are now mainly employed in clinic studies. Several studies reported as treatments with focal vibratory (FVT) can influence neuromuscular parameters also in healthy people. However, the application modalities and the consequent effects are remarkably fragmented. This paper aims to review these studies and to characterize the FVT effectiveness on long-term conditional capacities in relation to FVT characteristics. A systematic search of studies published from 1985 to 2020 in English on healthcare databases was performed. Articles had to meet the following criteria: (1) treatment based on a locally applied vibration on muscle belly or tendon; (2) healthy adults involved; (3) outcomes time analysis enduring for more than 24 h. Twelve studies were found, all of them presented an excellent quality score of ≥75%. All selected papers reported positive changes, comparable with traditional long-lasting training effects. Muscle force and power were the most investigated parameters. The after-effects persisted for up to several months. Among the different FV administration modalities, the most effective seems to show a stimulus frequency of ≈100 Hz, repeated more times within three-five days on a voluntary contracted muscle.

Sensory inflow manipulation induces learning-like phenomena in motor behavior.

PURPOSE: Perceptual and goal-directed behaviors may be improved by repetitive sensory stimulations without practice-based training. Focal muscle vibration (f-MV) modulating the spatiotemporal properties of proprioceptive inflow is well-suited to investigate the effectiveness of sensory stimulation in influencing motor outcomes. Thus, in this study, we verified whether optimized f-MV stimulation patterns might affect motor control of upper limb movements. METHODS: To answer this question, we vibrated the slightly tonically contracted anterior deltoid (AD), posterior deltoid (PD), and pectoralis major muscles in different combinations in forty healthy subjects at a frequency of 100 Hz for 10 min in single or repetitive administrations. We evaluated the vibration effect immediately after f-MV application on upper limb targeted movements tasks, and one week later. We assessed target accuracy, movement mean and peak speed, and normalized Jerk using a 3D optoelectronic motion capture system. Besides, we evaluated AD and PD activity during the tasks using wireless electromyography. RESULTS: We found that f-MV may induce increases (p < 0.05) in movement accuracy, mean speed and smoothness, and changes (p < 0.05) in the electromyographic activity. The main effects of f-MV occurred overtime after repetitive vibration of the AD and PD muscles. CONCLUSION: Thus, in healthy subjects, optimized f-MV stimulation patterns might over time affect the motor control of the upper limb movement. This finding implies that f-MV may improve the individual's ability to produce expected motor outcomes and suggests that it may be used to boost motor skills and learning during training and to support functional recovery in rehabilitation.

17 beta-estradiol synthesis modulates cerebellar dependent motor memory formation in adult male rats.

Neurosteroid 17 beta-estradiol (E2) is a steroid synthesized de novo in the nervous system that might influence neuronal activity and behavior. Nevertheless, the impact of E2 on the functioning of those neural systems in which it is slightly synthesized is less questioned. The vestibulo-ocular reflex (VOR) adaptation, may provide an ideal arena for investigating this issue. Indeed, E2 modulates cerebellar parallel fiber-Purkinje cell synaptic plasticity that underlies encoding of VOR adaptation. Moreover, aromatase expression in the cerebellum of adult rodents is maintained at very low levels and localized to Purkinje cells. The significance of age-related maintenance of low levels of aromatase expression in the cerebellum on behavior, however, has yet to be explored. Our aim in this study was to determine whether E2 synthesis exerts an effective and persistent modulation of VOR adaptation in adult male rats. To answer this question, we investigated the acute effect of blocking E2 synthesis on gain increases and decreases in VOR adaptation using an oral dose (2.5 mg/kg) of the aromatase inhibitor Letrozole in peri-pubertal and post-pubertal male rats. We found that Letrozole acutely impaired gain increases and decreases in VOR adaptation without altering basal ocular-motor performance and that these effects were similar in peri-pubertal and post-pubertal rats. Thus, in adult male rats neurosteroid E2 effectively modulates VOR adaptation in both of the periods studied. These findings imply that the adult cerebellum uses E2 synthesis for modulating motor memory formation and suggest that low and extremely localized E2 production may play a role in adaptive phenomena.

Sensorimotor Control of the Shoulder in Professional Volleyball Players With Isolated Infraspinatus Muscle Atrophy.

CONTEXT: Isolated infraspinatus muscle atrophy (IIMA) affects only the hitting shoulder of overhead-activity athletes and is caused by suprascapular nerve neuropathy. No study has assessed the static and dynamic stability of the shoulder in overhead professional athletes with IIMA to reveal possible shoulder sensorimotor alterations. OBJECTIVE: To assess the shoulder static stability, dynamic stability, and strength in professional volleyball players with IIMA and in healthy control players. DESIGN: Cross-sectional study. SETTING: Research lab. PATIENTS OR OTHER PARTICIPANTS: A total of 24 male professional volleyball players (12 players with diagnosed IIMA and 12 healthy players) recruited from local volleyball teams. INTERVENTION(S): Static stability was evaluated with 2 independent force platforms, and dynamic stability was assessed with the "Upper Quarter Y Balance Test." MAIN OUTCOME MEASURE(S): The static stability assessment was conducted in different support (single hand and both hands) and vision (open and closed eyes) conditions. Data from each test were analyzed with analysis of variance and paired t-test models to highlight statistical differences within and between groups. RESULTS: In addition to reduced abduction and external rotation strength, athletes with IIMA consistently demonstrated significant less static (P < .001) and dynamic stability (P < .001), compared with the contralateral shoulder and with healthy athletes. Closed eyes condition significantly enhanced the static stability deficit of the shoulder with IIMA (P = .04 and P = .03 for both hand and single hand support, respectively) but had no effect on healthy contralateral and healthy players' shoulders. CONCLUSIONS: This study highlights an impairment of the sensorimotor control system of the shoulder with IIMA, which likely results from both proprioceptive and strength deficits. This condition could yield subtle alteration in the functional use of the shoulder and predispose it to acute or overuse injuries. The results of this study may help athletic trainers and physical/physiotherapists to prevent shoulder injuries and create to specific proprioceptive and neuromuscular training programs.

Acute inhibition of estradiol synthesis impacts vestibulo-ocular reflex adaptation and cerebellar long-term potentiation in male rats.

The vestibulo-ocular reflex (VOR) adaptation is an ideal model for investigating how the neurosteroid 17 beta-estradiol (E2) contributes to the modification of behavior by regulating synaptic activities. We hypothesized that E2 impacts VOR adaptation by affecting cerebellar synaptic plasticity at the parallel fiber-Purkinje cell (PF) synapse. To verify this hypothesis, we investigated the acute effect of blocking E2 synthesis on gain increases and decreases in adaptation of the VOR in male rats using an oral dose (2.5 mg/kg) of the aromatase inhibitor letrozole. We also assessed the effect of letrozole on synaptic plasticity at the PF synapse in vitro, using cerebellar slices from male rats. We found that letrozole acutely impaired both gain increases and decreases adaptation of the VOR without altering basal ocular-motor performance. Moreover, letrozole prevented long-term potentiation at the PF synapse (PF-LTP) without affecting long-term depression (PF-LTD). Thus, in male rats neurosteroid E2 has a relevant impact on VOR adaptation and affects exclusively PF-LTP. These findings suggest that E2 might regulate changes in VOR adaptation by acting locally on cerebellar and extra-cerebellar synaptic plasticity sites.

Adaptive Changes in the Perception of Fast and Slow Movement at Different Head Positions.

BACKGROUND: This paper examines the subjective sense of orientation during asymmetric body rotations in normal subjects. METHODS: Self-motion perception was investigated in 10 healthy individuals during asymmetric whole-body rotation with different head orientations. Both on-vertical axis and off-vertical axis rotations were employed. Subjects tracked a remembered earth-fixed visual target while rotating in the dark for four cycles of asymmetric rotation (two half-sinusoidal cycles of the same amplitude, but of different duration). RESULTS: The rotations induced a bias in the perception of velocity (more pronounced with fast than with slow motion). At the end of rotation, a marked target position error (TPE) was present. For the on-vertical axis rotations, the TPE was no different if the rotations were performed with a 30° nose-down, a 60° nose-up, or a 90° side-down head tilt. With off-vertical axis rotations, the simultaneous activation of the semicircular canals and otolithic receptors produced a significant increase of TPE for all head positions. DISCUSSIONS: This difference between on-vertical and off-vertical axis rotation was probably partly due to the vestibular transfer function and partly due to different adaptation to the speed of rotation. Such a phenomenon might be generated in different components of the vestibular system. The adaptive process enhancing the perception of dynamic movement around the vertical axis is not related to the specific semicircular canals that are activated; the addition of an otolithic component results in a significant increase of the TPE.Panichi R, Occhigrossi C, Ferraresi A, Faralli M, Lucertini M, Pettorossi VE. Adaptive changes in the perception of fast and slow movement at different head positions. Aerosp Med Hum Perform. 2017; 88(5):463-468.

Knee flexion with quadriceps cocontraction: A new therapeutic exercise for the early stage of ACL rehabilitation.

Quadriceps strengthening exercises designed for the early phase of anterior cruciate ligament (ACL) rehabilitation should limit the anterior tibial translation developed by quadriceps contraction near full knee extension, in order to avoid excessive strain on the healing tissue. We hypothesize that knee-flexion exercises with simultaneous voluntary contraction of quadriceps (voluntary quadriceps cocontraction) can yield considerable levels of quadriceps activation while preventing the tibia from translating forward relative to the femur. Electromyographic activity in quadriceps and hamstring muscles was measured in 20 healthy males during isometric knee-flexion exercises executed near full knee extension with maximal voluntary effort of quadriceps cocontraction and external resistance (R) ranging from 0% to 60% of the 1-repetition maximum (1RM). Biomechanical modeling was applied to derive the shear (anterior/posterior) tibiofemoral force developed in each exercise condition. Isometric knee-flexion exercises with small external resistance (R=10% 1RM) and maximal voluntary effort of quadriceps cocontraction yielded a net posterior (ACL-unloading) tibial pull (P=0.005) and levels of activation of 32%, 50%, and 45% of maximum voluntary isometric contraction, for the rectus femoris, vastus medialis, and vastus lateralis, respectively. This exercise might potentially rank as one of the most appropriate quadriceps strengthening interventions in the early phase of ACL rehabilitation.

Voluntary enhanced cocontraction of hamstring muscles during open kinetic chain leg extension exercise: its potential unloading effect on the anterior cruciate ligament.

BACKGROUND: A number of research studies provide evidence that hamstring cocontraction during open kinetic chain knee extension exercises enhances tibiofemoral (TF) stability and reduces the strain on the anterior cruciate ligament. PURPOSE: To determine the possible increase in hamstring muscle coactivation caused by a voluntary cocontraction effort during open kinetic chain leg-extension exercises, and to assess whether an intentional hamstring cocontraction can completely suppress the anterior TF shear force during these exercises. STUDY DESIGN: Descriptive laboratory study. METHODS: Knee kinematics as well as electromyographic activity in the semitendinosus (ST), semimembranosus (SM), biceps femoris (BF), and quadriceps femoris muscles were measured in 20 healthy men during isotonic leg extension exercises with resistance (R) ranging from 10% to 80% of the 1-repetition maximum (1RM). The same exercises were also performed while the participants attempted to enhance hamstring coactivation through a voluntary cocontraction effort. The data served as input parameters for a model to calculate the shear and compressive TF forces in leg extension exercises for any set of coactivation patterns of the different hamstring muscles. RESULTS: For R≤ 40% 1RM, the peak coactivation levels obtained with intentional cocontraction (l) were significantly higher (P < 10(-3)) than those obtained without intentional cocontraction (l 0). For each hamstring muscle, maximum level l was reached at R = 30% 1RM, corresponding to 9.2%, 10.5%, and 24.5% maximum voluntary isometric contraction (MVIC) for the BF, ST, and SM, respectively, whereas the ratio l/l 0 reached its maximum at R = 20% 1RM and was approximately 2, 3, and 4 for the BF, SM, and ST, respectively. The voluntary enhanced coactivation level l obtained for R≤ 30% 1RM completely suppressed the anterior TF shear force developed by the quadriceps during the exercise. CONCLUSION: In leg extension exercises with resistance R≤ 40% 1RM, coactivation of the BF, SM, and ST can be significantly enhanced (up to 2, 3, and 4 times, respectively) by a voluntary hamstring cocontraction effort. The enhanced coactivation levels obtained for R≤ 30% 1RM can completely suppress the anterior TF shear force developed by the quadriceps during the exercise. CLINICAL RELEVANCE: This laboratory study suggests that leg extension exercise with intentional hamstring cocontraction may have the potential to be a safe and effective quadriceps-strengthening intervention in the early stages of rehabilitation programs for anterior cruciate ligament injury or reconstruction recovery. Further studies, including clinical trials, are needed to investigate the relevance of this therapeutic exercise in clinical practice.

Effect of transcranial direct current stimulation on vestibular-ocular and vestibulo-perceptual thresholds.

Transcranial direct current stimulation (tDCS) was used in 17 normal individuals to modulate vestibulo-ocular reflex (VOR) and self-motion perception rotational thresholds. The electrodes were applied over the temporoparietal junction bilaterally. Both vestibular nystagmic and perceptual thresholds were increased during as well as after tDCS stimulation. Body rotation was labeled as ipsilateral or contralateral to the anode side, but no difference was observed depending on the direction of rotation or hemisphere polarity. Threshold increase during tDCS was greater for VOR than for motion perception. 'Sham' stimulation had no effect on thresholds. We conclude that tDCS produces an immediate and sustained depression of cortical regions controlling VOR and movement perception. Temporoparietal areas appear to be involved in vestibular threshold modulation but the differential effects observed between VOR and perception suggest a partial dissociation between cortical processing of reflexive and perceptual responses.

Opposite long-term synaptic effects of 17ß-estradiol and 5α-dihydrotestosterone and localization of their receptors in the medial vestibular nucleus of rats.

In brainstem slices of male rats, we examined in single neurons of the medial vestibular nucleus (MVN) the effect of exogenous administration of estrogenic (17ß-estradiol, E2) and androgenic (5α-dihydrotestosterone, DHT) steroids on the synaptic response to vestibular afferent stimulation. By whole cell patch clamp recordings we showed that E2 induced synaptic long-term potentiation (LTP) that was cancelled by the subsequent administration of DHT. Conversely, DHT induced synaptic long-term depression (LTD) that was partially reversed by E2. The electrophysiological findings were supported by immunohistochemical analysis showing the presence of estrogen (ER: α and ß) and androgen receptors (AR) in the MVN neurons. We found that a large number of neurons were immunoreactive for ERα, ERß, and AR and most of them co-localized ERß and AR. We also showed the presence of P450-aromatase (ARO) in the MVN neurons, clearly proving that E2 can be locally synthesized in the MVN. On the whole, these results demonstrate a role of estrogenic and androgenic signals in modulating vestibular synaptic plasticity and suggest that the enhancement or depression of vestibular synaptic response may depend on the local conversion of T into E2 or DHT.

Joint torques and joint reaction forces during squatting with a forward or backward inclined Smith machine.

We developed a biomechanical model to determine the joint torques and loadings during squatting with a backward/forward-inclined Smith machine. The Smith squat allows a large variety of body positioning (trunk tilt, foot placement, combinations of joint angles) and easy control of weight distribution between forefoot and heel. These distinctive aspects of the exercise can be managed concurrently with the equipment inclination selected to unload specific joint structures while activating specific muscle groups. A backward (forward) equipment inclination decreases (increases) knee torque, and compressive tibiofemoral and patellofemoral forces, while enhances (depresses) hip and lumbosacral torques. For small knee flexion angles, the strain-force on the posterior cruciate ligament increases (decreases) with a backward (forward) equipment inclination, whereas for large knee flexion angles, this behavior is reversed. In the 0 to 60 degree range of knee flexion angles, loads on both cruciate ligaments may be simultaneously suppressed by a 30 degree backward equipment inclination and selecting, for each value of the knee angle, specific pairs of ankle and hip angles. The anterior cruciate ligament is safely maintained unloaded by squatting with backward equipment inclination and uniform/forward foot weight distribution. The conditions for the development of anterior cruciate ligament strain forces are clearly explained.

Influence of sex and estrous cycle on synaptic responses of the medial vestibular nuclei in rats: role of circulating 17ß-estradiol.

We investigated the possible influence of sex and estrous cycle on the synaptic responses of neurons in the medial vestibular nucleus (MVN) and their long-term modifications. In brain stem slices of male and female rats during proestrus (PE) and diestrus (DE), we evaluated the field potential evoked in the MVN by vestibular afferent stimulation. Here we find that in PE females the field potential had a lower threshold and higher amplitude than in DE females and in males and also that the stimulus-response curve was shifted to the left. Such difference is related to the level and cyclic fluctuation of circulating 17ß-estradiol (E(2)). This is supported by the exogenous administration of E(2) in DE females and males, with low levels of circulating E(2) that enhanced the field potential amplitude to values close to those of PE females. Sex and estrous cycle also influence the MVN synaptic plasticity. This has been shown by investigating the effect of testosterone (T) on the induction of long-term effects, since T is the precursor for the neural synthesis of E(2) (estrogenic pathway), which is involved in the induction of fast long-term potentiation (LTP), or of 5α-dihydrotestosterone (DHT, androgenic pathway) which mediates slow LTP and long-term depression (LTD). We found that T mostly induced LTD in PE females and no effect in DE females, while it only provoked fast LTP in males. We suggest that high level of circulating E(2) may interfere with the conversion of T, by inhibiting the neural estrogenic pathway and facilitating the androgenic one. On the whole these results demonstrate an influence of circulating E(2) on vestibular synaptic transmission and plasticity that in some cases may contribute to the sex and menstrual cycle dependence of symptoms in human vestibular pathology.

Cyclic estrogenic fluctuation influences synaptic transmission of the medial vestibular nuclei in female rats.

CONCLUSION: The estrous cycle in female rats influences the basal synaptic responsiveness and plasticity of the medial vestibular nucleus (MVN) neurons through different levels of circulating 17ß-estradiol (cE(2)). OBJECTIVE: The aim of this study was to verify, in the female rat, whether cyclic fluctuations of cE(2) influence long-term synaptic effects induced by high frequency afferent stimulation (HFS) in the MVN, since we found that HFS in the male rat induces fast long-term potentiation (fLTP), which depends on the neural synthesis of E(2) (nE(2)) from testosterone (T). METHODS: We analyzed the field potential (FP) evoked in the MVN by vestibular afferent stimulation, under basal conditions, and after HFS, in brainstem slices of female rats during high levels (proestrus, PE) and low levels (diestrus, DE) of cE(2). Selective blocking agents of converting T enzymes were used. RESULTS: Unlike in the male rat, HFS induced three effects: fLTP through T conversion into E(2), and slow LTP (sLTP) and long-term depression (LTD), through T conversion into DHT. The occurrence of these effects depended on the estrous cycle phase: the frequency of fLTP was higher in DE, and those of sLTP and LTD were higher in PE. Conversely, the basal FP was also higher in PE than in DE.

Improvement of stance control and muscle performance induced by focal muscle vibration in young-elderly women: a randomized controlled trial.

UNLABELLED: Filippi GM, Brunetti O, Botti FM, Panichi R, Roscini M, Camerota F, Cesari M, Pettorossi VE. Improvement of stance control and muscle performance induced by focal muscle vibration in young-elderly women: a randomized controlled trial. OBJECTIVE: To determine the effect of a particular protocol of mechanical vibration, applied focally and repeatedly (repeated muscle vibration [rMV]) on the quadriceps muscles, on stance and lower-extremity muscle power of young-elderly women. DESIGN: Double-blind randomized controlled trial; 3-month follow-up after intervention. SETTING: Human Physiology Laboratories, University of Perugia, Italy. PARTICIPANTS: Sedentary women volunteers (N=60), randomized in 3 groups (mean age +/- SD, 65.3+/-4.2y; range, 60-72). INTERVENTION: rMV (100Hz, 300-500microm, in three 10-minute sessions a day for 3 consecutive days) was applied to voluntary contracted quadriceps (vibrated and contracted group) and relaxed quadriceps (vibrated and relaxed group). A third group received placebo stimulation (nonvibrated group). MAIN OUTCOME MEASURES: Area of sway of the center of pressure, vertical jump height, and leg power. RESULTS: Twenty-four hours after the end of the complete series of applications, the area of sway of the center of pressure decreased significantly by approximately 20%, vertical jump increased by approximately 55%, and leg power increased by approximately 35%. These effects were maintained for at least 90 days after treatment. CONCLUSIONS: rMV is a short-lasting and noninvasive protocol that can significantly and persistently improve muscle performance in sedentary young-elderly women.

Long-term potentiation in the rat medial vestibular nuclei depends on locally synthesized 17beta-estradiol.

In male rat brainstem slices, we investigated the involvement of locally synthesized 17beta-estradiol (E(2)) in the induction in the medial vestibular nucleus (MVN) of long-term potentiation (LTP) by high-frequency stimulation (HFS) of the primary vestibular afferents. We demonstrated that the blockade of aromatase by letrozole or of E(2) receptors (ERalpha and ERbeta) by ICI 182,780 prevented the HFS-induced LTP of the N1 wave of the evoked field potential (FP) without affecting baseline responses. Only prolonged afferent activation could induce low LTP. In contrast, HFS applied under a combined blockade of GABA(A) receptors and aromatase or ERs was still able to induce LTP, but it was significantly lower and slower. These findings demonstrate that E(2) does not have a tonic influence on the activity of the MVN neurons and provide the first evidence of the crucial role played by local synthesis of E(2) in inducing LTP. We suggest that the synthesis of E(2) occurs after aromatase activation during HFS and facilitates the development of vestibular synaptic plasticity by influencing glutamate and GABA transmission.

Neurosteroid modulation of neuronal excitability and synaptic transmission in the rat medial vestibular nuclei.

In rat brainstem slices, we investigated the influence of the neurosteroids tetrahydrodeoxycorticosterone (THDOC) and allopregnanolone (ALLO) on the synaptically driven and spontaneous activity of vestibular neurons, by analysing their effects on the amplitude of the field potentials evoked in the medial vestibular nuclei (MVN) by vestibular afferent stimulation and on the spontaneous firing rate of MVN neurons. Furthermore, the interaction with gamma-aminobutyric acid (GABA) and glutamate receptors was analysed by using specific antagonists for GABA(A) (bicuculline), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/ kainate [2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo(f)quinoxaline-7-sulphonamide disodium salt (NBQX)], N-methyl-D-aspartate (NMDA) [D-(-)-2-amino-5-phosphonopentanoic acid (AP-5)] and group I metabotropic glutamate receptors (mGlu-I) [(R,S)-1-aminoindan-1,5-dicarboxylic acid (AIDA)] receptors. THDOC and ALLO evoked two opposite long-lasting effects, consisting of either a potentiation or a reduction of field potential and firing rate, which showed early and late components, occurring in conjunction or separately after neurosteroid application. The depressions depended on GABA(A) receptors, as they were abolished by bicuculline, while early potentiation involved glutamate AMPA/kainate receptors, as NBQX markedly reduced the incidence of early firing rate enhancement and, in the case of ALLO, even provoked depression. This suggests that THDOC and ALLO enhance the GABA(A) inhibitory influence on the MVN neurons and facilitate the AMPA/kainate facilitatory one. Conversely, a late potentiation effect, which was still induced after glutamate and GABA(A) receptor blockade, might involve a different mechanism. We conclude that the modulation of neuronal activity in the MVN by THDOC and ALLO, through their actions on GABA(A) and AMPA/kainate receptors, may have a physiological role in regulating the vestibular system function under normal conditions and during the stress response that accompanies many forms of vestibular dysfunction.

Activation of PAF-synthesizing enzymes in rat brain stem slices after LTP induction in the medial vestibular nuclei.

LysoPAF acetyltransferase (lysoPAF-AT) and PAF-synthesizing phosphocholinetransferase (PAF-PCT) are the two enzymes which catalyze the final reactions for the synthesis of PAF. Their activities, assayed in the homogenate of rat brain stem slices and under their optimal conditions, increased 5 min after high frequency stimulation of vestibular afferents, inducing LTP in the medial vestibular nuclei. The activity of phosphatidylcholine-synthesizing phosphocholinetransferase, was not affected. Sixty minutes from the induction of LTP, PAF-PCT activity, but not that of lysoPAF-AT, was still significantly higher with respect to 5 min test stimulated control. We used AP-5 to verify whether this increase was strictly dependent upon LTP induction, which requires NMDA receptor activation. In AP-5 treated slices, lysoPAF-acetyltransferase and PAF-synthesizing phosphocholinetransferase activities increased, but they were reduced after high frequency stimulation under AP-5. In conclusion, we have demonstrated that the activities of PAF-synthesizing enzymes are activated soon after the induction of LTP and that this effect is linked to the activation of NMDA-receptors. We suggest that the enzyme activation by AP-5, preventing LTP, might be due to glutamate enhancement but, in neurons showing LTP and under normal conditions, the activation of potentiation mechanisms is critical for the enhancement of enzyme activities.