Transmission of Predictable Sensory Signals to the Cerebellum via Climbing Fiber Pathways Is Gated during Exploratory Behavior

International audiencePathways arising from the periphery that target the inferior olive [spino-olivocerebellar pathways (SOCPs)] are a vital source of information to the cerebellum and are modulated (gated) during active movements. This limits their ability to forward signals to climbing fibers in the cerebellar cortex. We tested the hypothesis that the temporal pattern of gating is related to the predictability of a sensory signal. Low-intensity electrical stimulation of the ipsilateral hindlimb in awake rats evoked field potentials in the C1 zone in the copula pyramidis of the cerebellar cortex. Responses had an onset latency of 12.5 +/- 0.3 ms and were either short or long duration (8.7 +/- 0.1 vs 31.2 +/- 0.3 ms, respectively). Both types of response were shown to be mainly climbing fiber in origin and therefore evoked by transmission in hindlimb SOCPs. Changes in response size (area of field, millivolts per millisecond) were used to monitor differences in transmission during rest and three phases of rearing: phase 1, rearing up; phase 2, upright; and phase 3, rearing down. Responses evoked during phase 2 were similar in size to rest but were smaller during phases 1 and 3, i.e., transmission was reduced during active movement when self-generated (predictable) sensory signals from the hindlimbs are likely to occur. To test whether the pattern of gating was related to the predictability of the sensory signal, some animals received the hindlimb stimulation only during phase 2. Over similar to 10 d, the responses became progressively smaller in size, consistent with gating-out transmission of predictable sensory signals relayed via SOCPs

THE EFFECT OF MEASUREMENT ANGLE ON APPROXIMATIONS OF MAXIMUM JOINT TORQUE

The purpose of this study was to investigate the underestimation of maximum knee joint torque using a single joint-angle position for a variety of realistic torque-angle curves. The maximum force production capability of the knee flexors and knee extensors was modelled using literature-based parameters to define a quadratic torque-angle relationship. Model parameters were varied within a normative range and simulated measured torque was compared to true peak torque (model) for a series of commonly tested joint angles. Measurements furthest from the optimal angle for maximum strength were associated with underestimated torques that were 96% and 80% lower than true peak torque. Therefore, it is essential that knee joint torque is measured as close to the optimal angle as possible when attempting to determine maximum strength capability using a single discrete measurement

S191 Cerebellar contributions to fear behaviour

The cerebellar - periaqueductal grey connection is a critical component of the neural network subserving emotionally related freezing behaviour

Cerebellar modulation of memory encoding in the periaqueductal grey and fear behaviour

The pivotal role of the periaqueductal grey (PAG) in fear learning is reinforced by the identification of neurons in male rat ventrolateral PAG (vlPAG) that encode fear memory through signalling the onset and offset of an auditory-conditioned stimulus during presentation of the unreinforced conditioned tone (CS+) during retrieval. Some units only display CS+ onset or offset responses, and the two signals differ in extinction sensitivity, suggesting that they are independent of each other. In addition, understanding cerebellar contributions to survival circuits is advanced by the discovery that (i) reversible inactivation of the medial cerebellar nucleus (MCN) during fear consolidation leads in subsequent retrieval to (a) disruption of the temporal precision of vlPAG offset, but not onset responses to CS+, and (b) an increase in duration of freezing behaviour. And (ii) chemogenetic manipulation of the MCN-vlPAG projection during fear acquisition (a) reduces the occurrence of fear-related ultrasonic vocalisations, and (b) during subsequent retrieval, slows the extinction rate of fear-related freezing. These findings show that the cerebellum is part of the survival network that regulates fear memory processes at multiple timescales and in multiple ways, raising the possibility that dysfunctional interactions in the cerebellar-survival network may underlie fear-related disorders and comorbidities

Biomechanical locomotion adaptations on uneven surfaces can be simulated with a randomly deforming shoe midsole

Background: A shoe with unsystematic perturbations, similar to natural uneven terrain, may offer an enhanced training stimulus over current unstable footwear technologies. This study compared the instability of a shoe with unpredictably random midsole deformations, an irregular surface and a control shoe-surface whilst treadmill walking and running. Methods: Three-dimensional kinematics and electromyography were recorded of the lower limb in 18 active males. Gait cycle characteristics, joint angles at initial ground contact and maximum values during stance, and muscle activations prior to initial contact and during loading were analysed. Perceived stability, injury-risk and energy consumption were evaluated. Instability was assessed by movement variability, muscular activations and subjective ratings. Results: Posture alterations at initial contact revealed active adaptations in the irregular midsole and irregular surface to maintain stability whilst walking and running. Variability of the gait cycle and lower limb kinematics increased on the irregular surface compared to the control across locomotion types. Similarly increased variability (coefficient of variation) were found in the irregular midsole compared to the control for frontal ankle motion (walk: 31.1 and 14.9, run: 28.1 and 11.6), maximum sagittal knee angle (walk: 7.6 and 4.8, run: 2.8 and 2.4), and global gait characteristics during walking only (2.1 ± 0.5 and 1.6 ± 0.3). Tibialis anterior pre-activation reduced and gastrocnemius activation increased in the irregular midsole compared to the control across locomotion types. During running, peroneus longus activation increased in the irregular midsole and irregular surface. Conclusions: Results indicate random shoe midsole deformations enhanced instability relative to the control and simulated certain locomotion adaptations of the irregular surface, although less pronounced. Thus, a shoe with unpredictable instability revealed potential as a novel instability-training device

Footwear insoles with higher frictional properties enhance performance by reducing in-shoe sliding during rapid changes of direction

A novel 3D motion capture analysis assessed the efficacy of insoles in maintaining the foot position on the midsole platform inside the shoe during rapid change of direction manoeuvres used in team sports. An insole (TI) with increased static (35%) and dynamic (49%) coefficient of friction compared to a regular insole (SI) was tested. Change of direction performance was faster (p<.001) and perceived to be faster (p<.001) in TI compared to SI. Participants utilised greater coefficient of friction in TI compared to SI during a complete turn, but not during a 20 degree side-cut. In-shoe foot sliding reduced across the forefoot and midfoot during the braking phase of the turn and in the rearfoot during the side-cut in TI. Greater in-shoe foot sliding occurred in the turn than the side-cut across all foot regions. Results provide guidance for athletic footwear design to help limit in-shoe foot sliding and improve change of direction performance

Subjective embodiment during the rubber hand illusion predicts severity of premonitory sensations and tics in Tourette Syndrome

In Tourette Syndrome, the expression of tics and commonly preceding premonitory sensations is associated with perturbed subjective feelings of self-control and agency. We compared responses to the Rubber Hand Illusion in 23 adults with TS and 22 controls. Both TS and control participants reported equivalent subjective embodiment of the artificial hand: feelings of ownership, location, and agency were greater during synchronous visuo-tactile stimulation, compared to asynchronous. However, individuals with TS did not manifest greater proprioceptive drift, an objective marker of embodiment observed in controls. An 'embodiment prediction error' index of the difference between subjective embodiment and objective proprioceptive drift correlated with severity of premonitory sensations. Feelings of ownership also correlated with premonitory sensation severity, and feelings of agency with tic severity. These findings suggest that subjective bodily ownership, as measured by the rubber hand illusion, contributes to susceptibility to the premonitory sensations that may be a precipitating factor in tics

Cerebellar Modules and Their Role as Operational Cerebellar Processing Units

The compartmentalization of the cerebellum into modules is often used to discuss its function. What, exactly, can be considered a module, how do they operate, can they be subdivided and do they act individually or in concert are only some of the key questions discussed in this consensus paper. Experts studying cerebellar compartmentalization give their insights on the structure and function of cerebellar modules, with the aim of providing an up-to-date review of the extensive literature on this subject. Starting with an historical perspective indicating that the basis of the modular organization is formed by matching olivocorticonuclear connectivity, this is followed by consideration of anatomical and chemical modular boundaries, revealing a relation between anatomical, chemical, and physiological borders. In addition, the question is asked what the smallest operational unit of the cerebellum might be. Furthermore, it has become clear that chemical diversity of Purkinje cells also results in diversity of information processing between cerebellar modules. An additional important consideration is the relation between modular compartmentalization and the organization of the mossy fiber system, resulting in the concept of modular plasticity. Finally, examination of cerebellar output patterns suggesting cooperation between modules and recent work on modular aspects of emotional behavior are discussed. Despite the general consensus that the cerebellum has a modular organization, many questions remain. The authors hope that this joint review will inspire future cerebellar research so that we are better able to understand how this brain structure makes its vital contribution to behavior in its most general form

Control of human endometrial stromal cell motility by PDGF-BB, HB-EGF and trophoblast-secreted factors

Human implantation involves extensive tissue remodeling at the fetal-maternal interface. It is becoming increasingly evident that not only trophoblast, but also decidualizing endometrial stromal cells are inherently motile and invasive, and likely contribute to the highly dynamic processes at the implantation site. The present study was undertaken to further characterize the mechanisms involved in the regulation of endometrial stromal cell motility and to identify trophoblast-derived factors that modulate migration. Among local growth factors known to be present at the time of implantation, heparin-binding epidermal growth factor-like growth factor (HB-EGF) triggered chemotaxis (directed locomotion), whereas platelet-derived growth factor (PDGF)-BB elicited both chemotaxis and chemokinesis (non-directed locomotion) of endometrial stromal cells. Supernatants of the trophoblast cell line AC-1M88 and of first trimester villous explant cultures stimulated chemotaxis but not chemokinesis. Proteome profiling for cytokines and angiogenesis factors revealed neither PDGF-BB nor HB-EGF in conditioned media from trophoblast cells or villous explants, while placental growth factor, vascular endothelial growth factor and PDGF-AA were identified as prominent secretory products. Among these, only PDGF-AA triggered endometrial stromal cell chemotaxis. Neutralization of PDGF-AA in trophoblast conditioned media, however, did not diminish chemoattractant activity, suggesting the presence of additional trophoblast-derived chemotactic factors. Pathway inhibitor studies revealed ERK1/2, PI3 kinase/Akt and p38 signaling as relevant for chemotactic motility, whereas chemokinesis depended primarily on PI3 kinase/Akt activation. Both chemotaxis and chemokinesis were stimulated upon inhibition of Rho-associated, coiled-coil containing protein kinase. The chemotactic response to trophoblast secretions was not blunted by inhibition of isolated signaling cascades, indicating activation of overlapping pathways in trophoblast-endometrial communication. In conclusion, trophoblast signals attract endometrial stromal cells, while PDGF-BB and HB-EGF, although not identified as trophoblast-derived, are local growth factors that may serve to fine-tune directed and non-directed migration at the implantation site