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

Sensory inflow manipulation induces learning-like phenomena in motor behavior

© 2020, Springer-Verlag GmbH Germany, part of Springer Nature. 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 \u3c 0.05) in movement accuracy, mean speed and smoothness, and changes (p \u3c 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

Joint torques and tibiofemoral joint reaction force in the bodyweight "wall squat" therapeutic exercise

This study provides a biomechanical analysis of the bodyweight wall-squat exercise considering four exercise variants: knee angle; horizontal hip-ankle distance (d); shift between the rearfoot and forefoot of the centre of pressure (xGR) of the ground reaction force; back supported via the scapular or pelvic zone. The ankle and hip angles corresponding to a given knee angle can be modulated, changing the distance d, to manage limitation in lumbopelvic and ankle mobility. The knee-extensor muscles can be overloaded (250 Nm muscle torque) with knees flexed at 90°, back supported through the pelvic zone, and feet away from the wall (d = 50 cm). Scapular support, xGR at forefoot, and d = 50 cm, yield a higher level of muscle-torque for hip-extension (130 Nm) and knee-flexion (65 Nm), with knees at 90° of flexion or near full extension, respectively. Ankle-dorsiflexion (plantarflexion) muscle torque up to 40 Nm is reached with xGR at the forefoot (rearfoot). This study may aid trainers and therapists to finely modulate the muscle torques (up to the above-mentioned levels) by an appropriate selection of exercise variants for training or rehabilitation purposes. Low levels (60 N) of anterior tibial pull may occur near 25° of knee flexion with xGR at the rearfoot

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

Dynamic functions of GABA signaling during granule cell maturation

The dentate gyrus is one of the few areas of the brain where new neurons are generated throughout life. Neural activity influences multiple stages of neurogenesis, thereby allowing experience to regulate the production of new neurons. It is now well established that GABAA receptor-mediated signaling plays a pivotal role in mediating activity-dependent regulation of adult neurogenesis. GABA first acts as a trophic signal that depolarizes progenitors and early post mitotic granule cells, enabling network activity to control molecular cascades essential for proliferation, survival and growth. Following the development of glutamatergic synaptic inputs, GABA signaling switches from excitatory to inhibitory. Thereafter robust synaptic inhibition enforces low spiking probability of granule cells in response to cortical excitatory inputs and maintains the sparse activity patterns characteristic of this brain region. Here we review these dynamic functions of GABA across granule cell maturation, focusing on the potential role of specific interneuron circuits at progressive developmental stages. We further highlight questions that remain unanswered about GABA signaling in granule cell development and excitability

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

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

© 2018 Elsevier Inc. 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