Biology subjects

't Hart, B.

Publications and source records attributed to 't Hart, B..

3 recordsLinked to original sources

bioRxiv2019

Targeting MOG to skin macrophages prevents EAE in macaques through TGFβ-induced peripheral tolerance

To study the effect of vaccination on tolerization to the myelin antigen MOG we used a macaque model of experimental autoimmune encephalitis (EAE) in which immunization with recombinant human myelin oligodendrocyte glycoprotein (rhMOG) elicits brain inflammation and demyelination mediated by MOG-specific autoreactive CD4+ T lymphocytes and anti-MOG IgG. For antigen targeting to tolerizing antigen presenting cells, we used a recombinant antibody directed to the Dendritic Cells (DC)-Asialoglycoprotein receptor (DC-ASGPR). The intradermal administration of an anti-DC-ASGPR-MOG fusion protein, but not a control anti-DC-ASGPR-PSA (prostate specific antigen) protein, protected monkeys committed to develop EAE. Although effective treatment did not modify anti-MOG IgG production, it prevented the CD4+ T lymphocyte activation and pro-inflammatory cytokine production. Moreover, animals treated with anti-DC-ASGPR-MOG experienced a rise of MOG-specific CD4+CD25+FOXP3+CD39+ regulatory T cells as well as a TGF{beta}1, TGF{beta}2 and IL-8 upsurge after rhMOG re-immunization. Our results indicate that the pathogenicity of autoantibodies directed to MOG is mitigated in the presence of MOG-specific regulatory lymphocytes. This vaccination scheme appears suitable to treat relapsing autoimmune diseases with identified autoantigens such as that harboring anti-MOG or anti-AQP4 autoantibodies.

immunology↗

bioRxiv2018

The effects of awareness of the perturbation during motor adaptation on hand localization

Explicit awareness of a task is often evoked during rehabilitation and sports training with the intention of accelerating learning and improving performance. However, the effects of awareness of perturbations on the resulting sensory and motor changes produced during motor learning are not well understood. Here, we use explicit instructions as well as large rotation sizes to generate awareness of the perturbation during a visuomotor rotation task and test the resulting changes in both perceived and predicted sensory consequences as well as implicit motor changes.\n\nWe split participants into 4 groups which differ in both magnitude of the rotation (either 30{degrees} or 60{degrees}) during adaptation, and whether they receive a strategy to counter the rotation or not prior to adaptation. Performance benefits of explicit instruction are largest during early adaptation but continued to lead to improved performance through 90 trials of training. We show that with either instruction, or with large perturbations, participants become aware of countering the rotation. However, we find a base amount of implicit learning, with equal magnitudes, across all groups, even when asked to exclude any strategies while reaching with no visual feedback of the hand.\n\nParticipants also estimate the location of the unseen hand when it is moved by the robot (passive localization) and when they generate their own movement (active localization) following adaptation. These learning-induced shifts in estimates of hand position reflect both proprioceptive recalibration and updates in the predicted consequences of movements. We find that these estimates of felt hand position, which reflect updates in both proprioception and efference based estimates of hand position, shift significantly for all groups and were not modulated by either instruction or perturbation size.\n\nOur results indicate that not all processes of motor learning benefit from an explicit awareness of the task. Particularly, proprioceptive recalibration and the updating of predicted sensory consequences are largely implicit processes.

neuroscience↗

bioRxiv2018

Motor Learning Without Moving: Proprioceptive and Predictive Hand Localization After Passive Visuoproprioceptive Discrepancy Training

An accurate estimate of limb position is necessary for movement planning, before and after motor learning. Where we localize our unseen hand after a reach depends on felt hand position, or proprioception, but in studies and theories on motor adaptation this is quite often neglected in favour of predicted sensory consequences based on efference copies of motor commands. Both sources of information should contribute, so here we set out to further investigate how much of hand localization depends on proprioception and how much on predicted sensory consequences. We use a training paradigm combining robot controlled hand movements with rotated visual feedback that eliminates the possibility to update predicted sensory consequences ( exposure training), but still recalibrates proprioception, as well as a classic training paradigm with self-generated movements in another set of participants. After each kind of training we measure participants hand location estimates based on both efference-based predictions and afferent proprioceptive signals with self-generated hand movements ( active localization) as well as based on proprioception only with robot-generated movements ( passive localization). In the exposure training group, we find indistinguishable shifts in passive and active hand localization, but after classic training, active localization shifts more than passive, indicating a contribution from updated predicted sensory consequences. Both changes in open-loop reaches and hand localization are only slightly smaller after exposure training as compared to after classic training, confirming that proprioception plays a large role in estimating limb position and in planning movements, even after adaptation. (data: https://doi.org/10.17605/osf.io/zfdth, preprint: https://doi.org/10.1101/384941)

neuroscience↗