Non-steady locomotion in mice: a translational project on stability and modular organisation

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All vertebrates must cope daily with sources of instability: walking in a moving train or following prey in the tundra are very different but similarly challenging tasks. The loss of proprioception (ability to sense the position of own body parts) may severely affect the control of unsteady movement and is a symptom commonly associated with numerous neurological and orthopaedic conditions. However, very little is known about the role of proprioception in the fine tuning of locomotor patterns. The genetic removal of proprioceptors in mice, combined with the introduction of random perturbations are two powerful ways to emphasise the control mechanisms of locomotion. With the help of state of the art approaches, this project aims to give new insight into the link between proprioception and locomotion.In this project, a group of adult mice will walk on a special treadmill that can generate sudden movements in the anteroposterior (front/back) and mediolateral (right/left) directions. The response to a set of unexpected perturbations will be recorded in the form of electromyography (EMG, electrical activity of muscles) and hindlimb’s kinematics. Then, the same group of animals will be measured after selective genetic elimination of muscle spindles (a class of proprioceptors). In a translational effort, the same measurements will be conducted on healthy humans with intact muscle spindles in Berlin, Germany.The overwhelming number of muscles and joints in the body of vertebrates is a reminder of how complex the generation and control of movement is. The theory of muscle synergies states that movement is obtained by activating groups of functionally-related muscles in common patterns (called synergies) rather than by controlling muscles individually. Synergies will be extracted from EMG data to assess the modular organisation of movement. The dynamic stability of locomotion will be estimated using the concept of maximum Lyapunov exponent, a metric to represent the stability of a dynamical system over time.During my PhD, I found that the introduction of random perturbations in humans leads to an increased “robustness” (ability to cope with errors). This was visible in longer and less accurate muscle activation patterns. However, it was difficult to determine the reason for the increased robustness and whether it was linked to changes in proprioceptive feedback. Comparing the modular organisation of motion before and after muscle spindle removal will provide a deeper insight into the role of proprioception in the regulation of non-steady locomotion. A direct comparison with human data will support the translational character of the project. The hypothesis is that wild-type mice, like healthy humans, will respond to the unexpected perturbations by increasing the locomotor output’s robustness, a feature that might be visible in muscle spindle-deficient animals both during perturbed and unperturbed locomotion.