In recent years, several patients with chronic spinal cord injuries have been able to walk thanks to electrical implants. Now, the Swiss scientists who achieved this breakthrough have located the neurons that are activated and reorganised by electrical stimulation.

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Grégoire Courtine, a renowned Swiss neuroscientist at the Swiss Federal Institute of Technology in Lausanne (EPFL), has spent years researching how to make people with spinal cord damage walk again. He demonstrated his breakthroughs with rats in 2012, with monkeys in 2016, and with humans in 2018 and 2022, when he and his team got three paralysed patients to walk again with electrical spinal cord implants.

Now, in a new study published in Nature, Courtine and his group at EPFL’s NeuroRestore centre have identified the type of neuron that is activated and remodelled by spinal cord stimulation, allowing patients to stand up, walk and rebuild their muscles.

“We have shown that the improvement in motor function was maintained when the electrical stimulation was turned off, suggesting that the nerve fibres used for walking are reorganised.”
Grégoire Courtine, leader of the research.

In previous research, carried out in collaboration with neurosurgeon Jocelyne Bloch, nine patients paralysed by spinal cord injury were able to walk again – with the help of walkers and crutches – after being implanted with electrical stimulation implants.

These volunteers “underwent selective epidural electrical stimulation of the area that controls leg movement and were able to regain some motor function,” the authors say.

In the new study, “we demonstrated not only the efficacy of this therapy in all nine patients but also that the improvement in motor function was maintained after the neurorehabilitation process was completed and when the electrical stimulation was turned off. This suggested that the nerve fibres used for walking had been reorganised,” says Courtine.

The authors thought it was crucial to understanding exactly how this neuronal reorganisation occurs in order to develop more effective treatments and improve the lives of as many people as possible.

A surprising property of a family of neurons

To further this understanding, the team first studied the underlying mechanisms in mice. This revealed a surprising property in a family of neurons expressing the Vsx2 gene: while these neurons are not necessary for walking in healthy mice, they were essential for the recovery of motor function after spinal cord injury.

This discovery was the culmination of several phases of fundamental research. For the first time, scientists were able to visualise the activity of a patient’s spinal cord while walking. This led to an unexpected finding: during the process of spinal cord stimulation, neuronal activity decreased during walking. The authors hypothesised that this was due to neuronal activity being selectively directed towards the recovery of motor function.

The work reveals a property of a group of neurons expressing the Vsx2 gene: they are not required for walking in healthy mice, but are essential for the recovery of motor function after spinal cord injury.

To test their hypothesis, the team developed advanced molecular technology. “We have established the first 3D molecular mapping of the medulla of the spinal cord,” says Courtine. “Our model allowed us to observe the recovery process in greater detail, at the neuronal level,” he says.

Thanks to this highly accurate model, the team discovered that stimulation of the spinal cord activates Vsx2 neurons and that these neurons become increasingly important as the reorganisation process unfolds.

A versatile spinal implant
Stéphanie Lacour, a professor at EPFL, helped Courtine and Bloch’s team validate their findings with epidural implants developed in her lab. Lacour adapted the electrical stimulation devices by adding light-emitting diodes that allowed the system not only to stimulate the spinal cord, but also to deactivate the Vsx2 neurons on their own through an optogenetic process.

When the system was used in mice with a spinal cord injury, they immediately stopped walking as a result of the deactivation of the neurons, but there was no effect in healthy mice. This implies that Vsx2 neurons are necessary and sufficient for spinal cord stimulation therapies to be effective and lead to neuronal reorganisation.

“It is essential for neuroscientists to be able to understand the specific role that each neuronal subpopulation plays in a complex activity such as walking,” says Bloch. “The new study, in which nine clinical trial patients were able to regain some degree of motor function thanks to our implants, gives us valuable insight into the reorganisation process of spinal cord neurons.

Jordan Squair, who focuses on regenerative therapies within Neurorestore, adds: “This paves the way towards more targeted treatments for paralysed patients. We can now aim to manipulate these neurons to regenerate the spinal cord.