Biotechnology

After spinal cord injury, kinesthetic senses help restore movement, model


For nearly 50 years, jawless fish called lampreys have intrigued scientists for their remarkable ability to recover from spinal cord injuries. A new study reveals possible techniques by which lampreys can swim again, even though their nerve regeneration is rare.

Credit: From Christina Hamlet et al, PNAS, 2023, DOI: 10.1073/pnas.2213302120.

For nearly 50 years, jawless fish called lampreys have intrigued scientists for their remarkable ability to recover from spinal cord injuries. A new study reveals possible techniques by which lampreys can swim again, even though their nerve regeneration is rare.

Christina Hamlet of Bucknell University and collaborators, including Jennifer R. Morgan of the Marine Biological Laboratory (MBL), used a mathematical model to demonstrate how lampreys can use body-sensing feedback to regain swimming ability after spinal cord injury. This study could inspire new therapeutic approaches in humans or algorithms for locomotion in soft robots. This paper is published in Proceedings of the National Academy of Sciences.

“The point of this paper is that even in the absence of descending commands in those (spinal) lesions, you can increase sensory feedback and restore locomotion,” said Morgan, MBL Senior Scientist and Director of MBL’s Eugene Bell Center for Regenerative Biology. and Network Engineering.

Unlike humans and other mammals, lampreys recover quickly and almost completely even after severe injuries to the upper spinal cord. Morgan previously found that while nerve regeneration aids recovery in lampreys, it doesn’t tell the full story. Only a small proportion of neurons and nerve connections are restored in spinal cord injuries, so they must employ other mechanisms.

“I had all these questions about how it could work. How can you get a functioning nervous system with a few small, sparse connections? he asked.

Scientists have hypothesized that lampreys may use body-sensing feedback (called proprioception or kinesthesia) to guide their movements as well as descending nerve connections in the spinal cord. Morgan has reached out to discuss this with a longtime friend from MBL, Eric Tytell, Associate Professor of Biology at Tufts University and former Whitman Center MBL Investigator. Eric has collaborated with Lisa Fauci, a Professor of Mathematics at Tulane University, and Christina Hamlet, who is a co-mentored postdoc at Tulane.

Tytell, Fauci, and Hamlet used a mathematical model to mimic the lamprey’s movements. They teamed up to “see if we can model some of the effects of sensory feedback on swimming behavior in lampreys,” said Hamlet, who is currently an Assistant Professor of Mathematics at Bucknell University.

The team began playing around with various lamprey spinal injury scenarios — including both biologically plausible and nonsensical ones — all of which assumed no nerve regeneration throughout the spinal cord lesion. This is what modeling is for, says Hamlet, “We can break things you can’t break in biology.” The model takes into account the indentation and stretching made in the body over the lesion and transmits that information throughout the body via the muscles, not the spinal cord.

Even with moderate amounts of sensory feedback, the model showed surprising recovery of swimming patterns in a biologically plausible model. Stronger sensory feedback leads to greater improvements.

Because lampreys regrow some of their neurons after a lesion and therefore have brain-derived commands to drive locomotion, they may require less sensory feedback than models. The team hopes to add neural regeneration to the model and test how it affects movement and interacts with sensory feedback.

“If you have a good computational model, you can go through a lot more manipulation scenarios than is practical with experimentation,” says Morgan.

The team hopes that this study and future research will contribute to therapies for humans with spinal cord injuries and diseases that affect movement. Brain machine interfaces and stimulator devices are starting to incorporate body-sensing feedback to create smoother movements after injury, and this research could inform the amount and type of feedback humans need.

“Whether you’re an animal like a lamprey that[heals]spontaneously or a human that needs to be given medication or an electrical stimulator device, it gets to a point where you have a few things in their proper places and then reuse what’s already there. there has to be more to achieve than trying to recapitulate the original, identical pattern of synaptic connection and growth,” said Morgan.

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That Marine Biology Laboratory (MBL) is dedicated to scientific discovery – exploring basic biology, understanding marine and environmental biodiversity, and informing the human condition through research and education. Founded in Woods Hole, Massachusetts in 1888, MBL is a private, for-profit institution and an affiliate of the University of Chicago.




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