Marco Milano, Ecole Polytechnique Fédérale de Lausanne, Geneva, Switzerland

Integrating regenerating circuits through rehabilitation training

Funded in: 2021, 2022

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Problem: Limited regrowth of damaged nerve fibers across injuries

Target: Merge biological nerve repair strategy with neuroprosthetic rehabilitation paradigms

Goal: Integrate and sculpt regrowing propriospinal axons into functional locomotor circuits


Spinal cord injury (SCI) severs the connections of nerve fibers from the brain to the spinal cord. Due to the limited ability of damaged nerve fibers to regrow across injuries, SCI can lead to permanent neurological deficits. In certain types of incomplete SCI, rehabilitation therapy can improve functional recovery by stimulating the reorganization of nerve fibers that have been spared by the incomplete injuries. In contrast, individuals that suffer from anatomically complete SCI have no spared nerve fibers that cross the injury site. Recovery from such complete injuries will require stimulating nerve fibers to regrow across the complete SCI lesions and to form new connections with nerve cells below the injury. The research team recently developed a biological repair strategy that achieves robust regrowth of a type of nerve fiber, known as ‘propriospinal axons,’ into and through anatomically complete SCI. These regrown nerve fibers were able to reestablish a significant return of electrophysiological conduction across lesions. However, as expected, there was no detectable improvement in locomotor function, consistent with the idea that newly regrown neural circuits formed after complete SCI will need to “relearn” how to become functional, much in the same way that during childhood development, newly forming circuits must learn how to become functional through practice and use. In the same manner, substantial evidence now indicates that newly regrown circuits will require targeted rehabilitation procedures that foster their integration into functional networks through use and training. Here, the team proposes to merge my biological nerve repair strategy with state-of the-art neuroprosthetic rehabilitation paradigms in order to integrate and sculpt these newly regrowing nerve fibers into functional locomotor circuits.