Scientists have mapped critical brain-to-spinal cord nerve connections that drive voluntary movement in forelimbs, an advance that may help treat people suffering from paralysis after a spine injury or stroke.
The study, published in the journal Cell Reports, is an important step towards rehabilitating motor circuits to help motor function recover after an injury or disease damages the central nervous system.
"The map described in this study should allow us to explore which corticospinal-spinal interneuron connections are good targets for repair and restoration of voluntary movement," said Yutaka Yoshida from Cincinnati Children's Hospital Medical Center in the US.
"More research is necessary before human therapies are possible, but this information is very helpful for future repair strategies. We now know which circuits need to be repaired," said Yoshida.
Little has been known about how the corticospinal network of nerve connections between the brain and spinal cord are organised and function together, researchers said.
Seemingly simple tasks like reaching or grabbing require precise coordination between sensory and motor information transmitted through these coordinated connections, they said
To map this connectivity, the scientists studied these circuits in laboratory mice - taking advantage of similar corticospinal connections in primates, cats, and rodents.
Yoshida and colleagues were able to track corticospinal connections from the brain's cerebral cortex near the top of the head down to the spinal cord.
They also traced the organisation and function of corticospinal circuits using mouse genetics, and a viral tracer (a de-armed rabies virus) that allowed investigators to highlight and capture images of these links.
The connections trace down through what is called the brain's internal capsule, then arrive at the caudal medulla of the brain just above the spinal cord.
From there they enter the spinal cord, crisscrossing deep inside the spine as they continue to protrude downwards and make additional connections, according to the researchers.
Yoshida said his team was able to develop a map of corticospinal neurons that control forelimb and sensory nerve impulses. They also identified specific neurons that control different skilled movements.
In these areas, the scientists show how the nerve fibres connect onto certain premotor interneurons and transmit impulses between neurons to trigger skilled movements.
This includes nerve fibres that express a transcription factor called Chx10, a regulator gene that instructs other genes to turn on or off to initiate biological functions.
Chx10 is linked to nervous system function in other parts of the body, including the eyes. When the researchers silenced Chx10 only in the cervical spinal cord, it hampered the animals' ability to reach for food.
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