Electromyographic and Stabilometric Analysis of the Static and Dynamic "Standing Bird Dog" Exercise.

(1) Background: The "bird dog" exercise is considered one of the most effective therapeutic exercises for lumbopelvic rehabilitation and the prevention and treatment of low back pain. The "standing bird dog" (SBD) exercise, executed in a single-leg stance, constitutes a natural and challenging variation in the "bird dog"; nevertheless, this exercise has not yet been investigated. This study provides a stabilometric and electromyographic analysis of the SBD performed in static and dynamic conditions and in ipsilateral and contralateral variations; (2) Methods: A time-synchronized motion capture system, wireless electromyography sensors, and triaxial force platform were used to analyze the selected SBD exercises; (3) Results: In dynamic conditions, the gluteus maximum, multifidus, lumbar erector spinae, and gluteus medius reached a mean activation level higher than in the static condition, with peak activation levels of 80%, 60%, 55%, and a 45% maximum voluntary isometric contraction, respectively. In the static condition, balance control was more challenging in the mediolateral compared to the anteroposterior direction. In the dynamic condition, the balance challenge was higher in the anteroposterior direction and higher than the static condition in both directions; (4) Conclusions: The SBD was proved to be effective for strengthening the hip and lumbar extensor muscles and provided a powerful challenge to single-leg balance control in both mediolateral and anteroposterior directions.

Induction and Cancellation of Self-Motion Misperception by Asymmetric Rotation in the Light.

Asymmetrical sinusoidal whole-body rotation sequences with half-cycles at different velocities induce self-motion misperception. This is due to an adaptive process of the vestibular system that progressively reduces the perception of slow motion and increases that of fast motion. It was found that perceptual responses were conditioned by four previous cycles of asymmetric rotation in the dark, as the perception of self-motion during slow and fast rotations remained altered for several minutes. Surprisingly, this conditioned misperception remained even when asymmetric stimulation was performed in the light, a state in which vision completely cancels out the perceptual error. This suggests that vision is unable to cancel the misadaptation in the vestibular system but corrects it downstream in the central perceptual processing. Interestingly, the internal vestibular perceptual misperception can be cancelled by a sequence of asymmetric rotations with fast/slow half-cycles in a direction opposite to that of the conditioning asymmetric rotations.

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.

Disruption of self-motion perception without vestibular reflex alteration in ménière's disease.

BACKGROUND: Self-motion misperception has been observed in vestibular patients during asymmetric body oscillations. This misperception is correlated with the patient's vestibular discomfort. OBJECTIVE: To investigate whether or not self-motion misperception persists in post-ictal patients with Ménière's disease (MD). METHODS: Twenty-eight MD patients were investigated while in the post-ictal interval. Self-motion perception was studied by examining the displacement of a memorized visual target after sequences of opposite directed fast-slow asymmetric whole body rotations in the dark. The difference in target representation was analyzed and correlated with the Dizziness Handicap Inventory (DHI) score. The vestibulo-ocular reflex (VOR) and clinical tests for ocular reflex were also evaluated. RESULTS: All MD patients showed a noticeable difference in target representation after asymmetric rotation depending on the direction of the fast/slow rotations. This side difference suggests disruption of motion perception. The DHI score was correlated with the amount of motion misperception. In contrast, VOR and clinical trials were altered in only half of these patients. CONCLUSIONS: Asymmetric rotation reveals disruption of self-motion perception in MD patients during the post-ictal interval, even in the absence of ocular reflex impairment. Motion misperception may cause persistent vestibular discomfort in these patients.

Effects of Voluntary Quadriceps-Hamstring Cocontraction on Tibiofemoral Force During Isometric Knee Extension and Knee Flexion Exercises With Constant External Resistance.

A biomechanical model has been developed to assess the effects of a voluntary effort of quadriceps-hamstring cocontraction on tibiofemoral force during isometric knee flexion and knee extension exercises with constant external resistance. The model establishes the analytic condition in the moment arms and traction angles of the quadriceps and hamstring muscles that determines the direction (anterior/posterior) of the tibiofemoral shear force developed by the cocontraction. This model also establishes the mechanical effect (loading/unloading) on the anterior cruciate ligament (ACL). At about 15° of knee flexion (where the ACL experiences its maximum quadriceps-induced strain) a voluntary quadriceps-hamstring cocontraction effort yields: (1) nearly the same enhancement in hamstring and quadriceps activation, (2) an increase in hamstring force about 1.5 times higher than that of the quadriceps, and (3) posterior (ACL unloading) tibial pull and compressive tibiofemoral force that increase linearly with the level of quadriceps and hamstring activation. The sensitivity of the results to intersubject variability in the posterior slope of the tibial plateau and muscle moment arms has been estimated with the use of anatomic data available in the literature. An anterior (ACL loading) tibial pull is actually developed at 15° of knee flexion by a voluntary effort of quadriceps-hamstring cocontraction as the posterior tibial slope exceeds 14°.

Auditory perception is influenced by the orientation of the trunk relative to a sound source.

The study investigated how hearing depends on the whole body, head and trunk orientation relative to a sound source. In normal hearing humans we examined auditory thresholds and their ability to recognize logatomes (bi-syllabic non-sense words) at different whole body, head and trunk rotation relative to a sound source. We found that auditory threshold was increased and logatome recognition was impaired when the body or the trunk were rotated 40° away from a sound source compared to when the body or the trunk was oriented towards the sound source. Conversely, no effects were seen when only the head was rotated. Further, an increase of thresholds and impairment of logatome recognition were also observed after unilateral vibration of dorsal neck muscles that induces, per se, long-lasting illusory trunk displacement relative to the head. Thus, our findings support the idea that processing of acoustic signals depends on where a sound is located within a reference system defined by the subject's trunk coordinates.

Mechanisms of Modulation of Automatic Scapulothoracic Muscle Contraction Timings.

Erected posture provides humans a large shoulder mobility that requires complex automatic muscle synergies to accomplish joint stability needs. This is evident in shoulder abduction, wherein the voluntary activation of glenohumeral muscles is coupled with an automatic recruitment of scapulothoracic muscles. Here, we investigated whether volitional modification of the scapular position, and dynamic scapular elevation, modulate the contraction timing of five shoulder muscles (middle deltoid, upper, middle and lower fiber of the trapezius, serratus anterior) during shoulder abduction. The results show matched contraction timings of the deltoid and upper trapezius across the scapular positions, whereas the contraction timings of the middle and lower fibers of the trapezius change secondary to the scapular position. These results might reflect different central strategies to coordinate the automatic sequences of contraction of the scapulothoracic muscles. This suggest a flexible and adaptable predisposition of the motor control system in exploring alternative solutions to accomplish the functional movement needs, such as the fulfillment of unconstrained movements. Intriguingly, the shoulder abduction may represent a powerful, non-invasive, and straightforward tool to deepen the understanding of the neural basis underlying the voluntary motor command modulation of the out-of-volition automatic muscle contractions.

De Novo Synthesized Estradiol: A Role in Modulating the Cerebellar Function.

The estrogen estradiol is a potent neuroactive steroid that may regulate brain structure and function. Although the effects of estradiol have been historically associated with gonadal secretion, the discovery that this steroid may be synthesized within the brain has expanded this traditional concept. Indeed, it is accepted that de novo synthesized estradiol in the nervous system (nE2) may modulate several aspects of neuronal physiology, including synaptic transmission and plasticity, thereby influencing a variety of behaviors. These modulations may be on a time scale of minutes via non-classical and often membrane-initiated mechanisms or hours and days by classical actions on gene transcription. Besides the high level, recent investigations in the cerebellum indicate that even a low aromatase expression can be related to the fast nE2 effect on brain functioning. These pieces of evidence point to the importance of an on-demand and localized nE2 synthesis to rapidly contribute to regulating the synaptic transmission. This review is geared at exploring a new scenario for the impact of estradiol on brain processes as it emerges from the nE2 action on cerebellar neurotransmission and cerebellum-dependent learning.

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.

Effects of scapular retraction/protraction position and scapular elevation on shoulder girdle muscle activity during glenohumeral abduction.

According to scapulohumeral rhythm, shoulder abduction is followed through scapular upward rotation to ensure joint mobility and stability. Of interest, the shoulder abduction can be performed holding the scapula in different positions and in association with scapular elevation, with possible effects on shoulder muscle activity. Therefore, the aim of the study was to analyze the activity of relevant shoulder muscles and the activity ratios between the scapulothoracic muscles, during shoulder abduction performed in different combinations of scapular position (neutral, retracted, protracted) and scapular elevation. The electromyographic activity of middle deltoid, serratus anterior, upper, middle and lower fibers of trapezius was recorded during shoulder abduction movements executed holding the scapula in neutral, retracted and protracted position, and subsequently a shoulder elevation movement. The activation of each muscle and the scapulothoracic muscles activity ratios were determined every 15 degrees, from 15° to 120° of abduction. Scapular retraction led to higher activation of the entire trapezius muscle, whereas protraction induced higher upper trapezius, middle deltoid and serratus anterior activity, along with lower activity of middle and lower trapezius. Shoulder elevation led to higher activity of the upper trapezius and middle deltoid. Moreover, it induced lower activation of the serratus anterior and middle and lower trapezius, thus leading to high ratios between the upper trapezius and the other scapulothoracic muscles, especially between 15 and 75 degrees of abduction. This study highlights that shoulder abduction performed with scapular protraction and in combination with scapular elevation leads to increased activity of the middle deltoid and upper trapezius, resulting in imbalances between the scapulothoracic muscles that could hamper the optimal scapulohumeral rhythm. The abduction performed in the aforementioned scapular conditions also induce potential reciprocal inhibition effects between the movers and stabilizers muscles of scapula, suggesting different motor control strategies of integrating a common shoulder movement with various modification of the scapular position.

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.

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.

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.

Residual Dizziness after Successful Repositioning Maneuver for Idiopathic Benign Paroxysmal Positional Vertigo: A Review.

The benign paroxysmal positional vertigo (BPPV) is a vestibular disorder cause of vertigo. The BPPV may be corrected mechanically by repositioning maneuvers but even after successful maneuvers, some patients report residual dizziness for a certain period afterward. Early recognition and treatment might decrease the incidence of residual dizziness in patients with BPPV, especially in those patients with psychiatric comorbidities and in the elderly, lowering the risk of falling. Many pathogenetic hypotheses for residual dizziness are under debate. The purpose of this review was to identify, evaluate and review recent researches about possible causal factors involved in residual dizziness and the implications on clinical practice. A literature search was performed using different databases such as Pubmed and Scopus. The following search terms were used: residual dizziness, otolithic membrane and BPPV. The search found a total of 1192 titles, which were reduced to 963 after a procedure of de-duplication of the found titles. The research was then restricted to an interval of time comprised between 2000 and 2016 for a total of 800 titles. Among these titles, only those including the terms benign paroxysmal positional vertigo were considered eligible for this review. Only publications in English language were taken into consideration and we excluded those with not available abstract. Finally, 90 abstracts were obtained and critically evaluated by two different Authors, and additional studies were identified by hand searching from the references of artiche of interest. Only 53 were included in this work.

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.

Low excitatory innervation balances high intrinsic excitability of immature dentate neurons.

Persistent neurogenesis in the dentate gyrus produces immature neurons with high intrinsic excitability and low levels of inhibition that are predicted to be more broadly responsive to afferent activity than mature neurons. Mounting evidence suggests that these immature neurons are necessary for generating distinct neural representations of similar contexts, but it is unclear how broadly responsive neurons help distinguish between similar patterns of afferent activity. Here we show that stimulation of the entorhinal cortex in mouse brain slices paradoxically generates spiking of mature neurons in the absence of immature neuron spiking. Immature neurons with high intrinsic excitability fail to spike due to insufficient excitatory drive that results from low innervation rather than silent synapses or low release probability. Our results suggest that low synaptic connectivity prevents immature neurons from responding broadly to cortical activity, potentially enabling excitable immature neurons to contribute to sparse and orthogonal dentate representations.

Long-lasting effects of neck muscle vibration and contraction on self-motion perception of vestibular origin.

OBJECTIVE: To show that neck proprioceptive input can induce long-term effects on vestibular-dependent self-motion perception. METHODS: Motion perception was assessed by measuring the subject's error in tracking in the dark the remembered position of a fixed target during whole-body yaw asymmetric rotation of a supporting platform, consisting in a fast rightward half-cycle and a slow leftward half-cycle returning the subject to the initial position. Neck muscles were relaxed or voluntarily contracted, and/or vibrated. Whole-body rotation was administered during or at various intervals after the vibration train. The tracking position error (TPE) at the end of the platform rotation was measured during and after the muscle conditioning maneuvers. RESULTS: Neck input produced immediate and sustained changes in the vestibular perceptual response to whole-body rotation. Vibration of the left sterno-cleido-mastoideus (SCM) or right splenius capitis (SC) or isometric neck muscle effort to rotate the head to the right enhanced the TPE by decreasing the perception of the slow rotation. The reverse effect was observed by activating the contralateral muscle. The effects persisted after the end of SCM conditioning, and slowly vanished within several hours, as tested by late asymmetric rotations. The aftereffect increased in amplitude and persistence by extending the duration of the vibration train (from 1 to 10min), augmenting the vibration frequency (from 5 to 100Hz) or contracting the vibrated muscle. Symmetric yaw rotation elicited a negligible TPE, upon which neck muscle vibrations were ineffective. CONCLUSIONS: Neck proprioceptive input induces enduring changes in vestibular-dependent self-motion perception, conditional on the vestibular stimulus feature, and on the side and the characteristics of vibration and status of vibrated muscles. This shows that our perception of whole-body yaw-rotation is not only dependent on accurate vestibular information, but is modulated by proprioceptive information related to previously experienced position of head with respect to trunk. SIGNIFICANCE: Tonic proprioceptive inflow, as might occur as a consequence of enduring or permanent head postures, can induce adaptive plastic changes in vestibular-dependent motion sensitiveness. These changes might be counteracted by vibration of selected neck muscles.

Distinct determinants of sparse activation during granule cell maturation.

Adult neurogenesis continually produces a small population of immature granule cells (GCs) within the dentate gyrus. The physiological properties of immature GCs distinguish them from the more numerous mature GCs and potentially enables distinct network functions. To test how the changing properties of developing GCs affect spiking behavior, we examined synaptic responses of mature and immature GCs in hippocampal slices from adult mice. Whereas synaptic inhibition restricted GC spiking at most stages of maturation, the relative influence of inhibition, excitatory synaptic drive, and intrinsic excitability shifted over the course of maturation. Mature GCs received profuse afferent innervation such that spiking was suppressed primarily by inhibition, whereas immature GC spiking was also limited by the strength of excitatory drive. Although the input resistance was a reliable indicator of maturation, it did not determine spiking probability at immature stages. Our results confirm the existence of a transient period during GC maturation when perforant path stimulation can generate a high probability of spiking, but also reveal that immature GC excitability is tempered by functional synaptic inhibition and reduced excitatory innervation, likely maintaining the sparse population activity observed in vivo.

Synaptic long-term potentiation and depression in the rat medial vestibular nuclei depend on neural activation of estrogenic and androgenic signals.

Estrogenic and androgenic steroids can be synthesised in the brain and rapidly modulate synaptic transmission and plasticity through direct interaction with membrane receptors for estrogens (ERs) and androgens (ARs). We used whole cell patch clamp recordings in brainstem slices of male rats to explore the influence of ER and AR activation and local synthesis of 17ß-estradiol (E2) and 5α-dihydrotestosterone (DHT) on the long-term synaptic changes induced in the neurons of the medial vestibular nucleus (MVN). Long-term depression (LTD) and long-term potentiation (LTP) caused by different patterns of high frequency stimulation (HFS) of the primary vestibular afferents were assayed under the blockade of ARs and ERs or in the presence of inhibitors for enzymes synthesizing DHT (5α-reductase) and E2 (P450-aromatase) from testosterone (T). We found that LTD is mediated by interaction of locally produced androgens with ARs and LTP by interaction of locally synthesized E2 with ERs. In fact, the AR block with flutamide prevented LTD while did not affect LTP, and the blockade of ERs with ICI 182,780 abolished LTP without influencing LTD. Moreover, the block of P450-aromatase with letrozole not only prevented the LTP induction, but inverted LTP into LTD. This LTD is likely due to the local activation of androgens, since it was abolished under blockade of ARs. Conversely, LTD was still induced in the presence of finasteride the inhibitor of 5α-reductase demonstrating that T is able to activate ARs and induce LTD even when DHT is not synthesized. This study demonstrates a key and opposite role of sex neurosteroids in the long-term synaptic changes of the MVN with a specific role of T-DHT for LTD and of E2 for LTP. Moreover, it suggests that different stimulation patterns can lead to LTD or LTP by specifically activating the enzymes involved in the synthesis of androgenic or estrogenic neurosteroids.

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.