Aya Takeoka, Vlaams Instituut voor Biotechonologie, Neuroelectronics Research Flanders, Leuven, Belgium

Dissection of network and cell type-specific contribution in motor recovery

Funded in: 2022, 2023, 2024

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Problem: Disconnection from the brain deprives the spinal cord of excitation
Target: Activity of defined nerve cell types alters locomotor recovery
Goal: Optimize electrical stimulation and identify a unique, gene expression profile

A severe spinal cord injury disrupts the brain and the spinal cord connection. While the built-in ability of the spinal cord to generate movements persists even after injury, disconnection from the brain deprives the spinal cord of excitation, leading to chronic motor impairment. Moreover, it is unknown whether nerve cells remain the same after a severe spinal cord injury and, if not, how they might change. The scientists` recent work shows that excitatory nerve cells can turn inhibitory after injury, making it challenging to drive muscle contractions.

Rehabilitative training facilitates motor recovery by promoting circuit reorganization through a specific type of excitatory nerve cells. For instance, a subgroup of excitatory nerve cells increases connections to nerve cells that directly influence muscle contractions. In addition, the same group of neurons remains excitable instead of becoming inhibitory nerve cells. Together, rehabilitative training regulates functions of spinal circuits below injury. As spinal cord injury patients rely on remaining brain input and the spinal cord to learn to walk again, scientists need to understand which nerve cells are engaged during training and recovery and how their activity patterns change over time. And the best way to study the change in activity patterns is by recording their firing patterns during walking.

Using a combination of genetic engineering, the researchers will study how the activity of defined nerve cell types alters locomotor recovery. Knowledge gained from this proposal will help 1) adapt and optimize configurations of epidural or transcutaneous electrodes so that excitation of an injured spinal cord can be applied in a task-specific manner, and 2) identify a unique, gene expression profile which may reveal potential therapeutic targets.