Scientists discover surprising memory capabilities of the spinal cord

Researchers at the RIKEN Center for Brain Science have discovered neural mechanisms in the spinal cord that enable brain-independent motor learning, potentially revolutionizing recovery therapies for spinal cord injuries.

Aya Takeoka and her team at the RIKEN Center for Brain Science in Japan have identified the neural pathways in the spinal cord that enable motor learning independently of the brain. Their research, published in the journal Science on April 11 found two critical groups of spinal cord neurons, one needed for new adaptive learning, and another for remembering adaptations once they have been learned. The findings could help scientists develop ways to support motor recovery after spinal cord injury.

Scientists have known for some time that the spinal cord’s motor output can be modified with exercise, even without a brain. This has been demonstrated most dramatically in headless insects, whose legs can still be trained to avoid external cues. Until now, no one has discovered exactly how this is possible, and without this insight the phenomenon is little more than an idiosyncratic fact. As Takeoka explains, “Understanding the underlying mechanism is essential if we want to understand the basis of movement automation in healthy people and use this knowledge to improve recovery after spinal cord injury.”

In this study, spinal cord participants learned to associate the position of a limb with an unpleasant experience of repositioning the limb after just 10 minutes, and retained a memory the next day. Spinals that received random unpleasantries did not learn. Credit: RIKEN

Before jumping into the neural circuitry, the researchers first developed an experimental setup that allowed them to study mouse spinal cord adaptation, both learning and remembering, without input from the brain. Each test had an experimental mouse and a control mouse with its hind legs dangling freely. If the experimental mouse’s hind leg hung down too much, it was electrically stimulated, mimicking something a mouse would want to avoid. The control mouse received the same stimulation at the same time, but was not linked to its own hind paw position.

Observations of immediate learning and memory retention

After just 10 minutes, they observed motor learning only in the experimental mice; their legs remained elevated and avoided any electrical stimulation. This result showed that the spinal cord can associate an unpleasant sensation with the leg position and adjust its motor output so that the leg avoids the unpleasant sensation, all without the need for a brain. Twenty-four hours later, they repeated the 10-minute test, but switched the experimental and control mice. The original experimental mice still held their legs up, indicating that the spinal cord retained a memory of past experiences, which hindered new learning.

After identifying both immediate learning and memory in the spinal cord, the team next looked for the neural circuits that make both possible. They used six types of transgenic mice, each with a different set of spinal neurons disabled, and tested them for motor learning and learning reversal. They found that the hind legs of mice did not adapt to avoid the electric shocks after neurons at the top of the spinal cord were disabled, especially those that express the gene.Ptf1a.

When they examined the mice during reversal learning, they found that silencing the Ptf1a-expressing neurons had no effect. Instead, there is a group of neurons in the lower, ventral part of the spinal cord that express the neurons And1 gene was crucial. When these neurons were silenced the day after avoidance learning, the spinal cord behaved as if they had never learned anything. The researchers also assessed memory on the second day by repeating the initial learning conditions. They found that in wild-type mice, the hindlimbs stabilized to reach the avoidance position faster than on the first day, indicating memory. Exciting the And1 neurons during recall increased this rate by 80%, indicating improved motor recall.

“These results not only challenge the prevailing idea that motor learning and memory are exclusively limited to brain circuits,” says Takeoka, “but we have also shown that we can manipulate motor memory at the spinal cord, which has implications for therapies designed to improve recovery after spinal cerebral hemorrhage. damage to the cord.”

Reference: “Two inhibitory neuronal classes control the acquisition and recall of spinal sensorimotor adaptation” by Simon Lavaud, Charlotte Bichara, Mattia D’Andola, Shu-Hao Yeh and Aya Takeoka, April 11, 2024, Science.
DOI: 10.1126/science.adf6801