Objectif Severe spinal cord injury leads to a range of disabilities, including permanent motor impairments that seriously diminish the patients’ quality of life. In the framework of an ERC Starting Grant, my team and I developed a pragmatic therapy that restored supraspinal control of leg movement after complete paralysis in rats. However, the mechanisms underlying the effects of this intervention remain unknown. This fundamental knowledge is pivotal to operate a disruptive conversion from our empirical approach to an evidence-based strategy with clinical perspectives. Our therapy, termed neuroprosthetic rehabilitation, acts over two time windows. Immediately, electrical and chemical spinal cord stimulations mediate motor control of the paralysed hindlimbs. In the long term, will-powered training regimens enabled by electrochemical stimulation and robotic assistance promote neuroplasticity of residual connections—an extensive rewiring that reestablishes voluntary movement. Here, we propose to identify the circuit-level remodelling, computational principles, and molecular cues that govern the immediate and long-term recovery of motor functions. To address this knowledge gap, we will use our unique neuroprosthetic platform and next-generation experimental techniques for longitudinal assessment of neuroplasticity and function in freely behaving mice. These techniques combine optogenetics, circuit-level inactivation techniques, unconstrained chronic calcium imaging, virus-mediated tract-tracing and genetic manipulations. Our strategy consists of deploying a judicious association of these experimental techniques to establish causality between the reorganisation of the motor circuitry and functional recovery. This project will fertilize frontier research with new knowledge and ideas, ultimately accelerating clinical implementation of safer and more efficacious therapies to improve the quality of life for spinal cord injured individuals. Champ scientifique engineering and technologymaterials engineeringfibersmedical and health sciencesclinical medicinephysiotherapynatural scienceschemical sciencesinorganic chemistryalkaline earth metalsmedical and health sciencesmedical biotechnologygenetic engineeringnatural sciencesphysical sciencesopticsmicroscopy Mots‑clés neurorehabilitation neuromodulation robotics locomotion neuroplasticity BDNF spinal cord injury mice Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Thème(s) ERC-CoG-2015 - ERC Consolidator Grant Appel à propositions ERC-2015-CoG Voir d’autres projets de cet appel Régime de financement ERC-COG - Consolidator Grant Institution d’accueil ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE Contribution nette de l'UE € 1 998 715,00 Adresse BATIMENT CE 3316 STATION 1 1015 Lausanne Suisse Voir sur la carte Région Schweiz/Suisse/Svizzera Région lémanique Vaud Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 1 998 715,00 Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution nette de l'UE Tout développer Tout réduire ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE Suisse Contribution nette de l'UE € 1 998 715,00 Adresse BATIMENT CE 3316 STATION 1 1015 Lausanne Voir sur la carte Région Schweiz/Suisse/Svizzera Région lémanique Vaud Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 1 998 715,00