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For nearly 50 years, a jawless fish called the lamprey has intrigued scientists because of its remarkable ability to recover from spinal cord injuries. A New research Despite sporadic nerve regeneration, lampreys reveal a potential strategy they can use to swim again.
Christina Hamlet of Bucknell University and Jennifer R. of the Marine Biological Laboratory (MBL). Collaborators, including Morgan, used a mathematical model to demonstrate how lampreys can use body-sensory feedback to regain swimming ability after spinal cord injury. The research could inspire new therapeutic approaches in humans or algorithms for motion in soft robots. The paper is published Proceedings of the National Academy of Sciences.
“The punchline of the paper is that even in the absence of descending command across the (spinal) lesion, you can enhance the sensory response and restore motion,” said Morgan, MBL senior scientist and director of MBL’s Eugene Bell Center for Regenerative Biology. and tissue engineering.
Unlike humans and other mammals, lampreys recover quickly and almost completely from severe spinal cord injury. Morgan previously discovered that although nerve regeneration helps lamprey recovery, it doesn’t tell the whole story. Only a small percentage of neurons and neuronal connections recover from spinal cord injury, so they must use another mechanism.
“I had all these questions about how it could possibly work. How do you get a functioning nervous system with a few small sparse connections?” Morgan asked.
The scientists hypothesized that lampreys may use body-sensing feedback (called proprioception or kinesthesia) to guide their movements in addition to descending nerve connections in the spinal cord. Morgan reached out to an old friend of his at MBL, Eric Titel, an associate professor of biology at Tufts University and a former investigator at the MBL Whitman Center, to discuss the matter. Eric was already collaborating with Lisa Fauci, professor of mathematics at Tulane University, and Christina Hamlett, who was a co-instructor postdoc at Tulane.
Tittle, Fauci and Hamlet were using mathematical models to simulate lampreys. They “wanted to see if we could model some of the effects of sensory feedback on swimming behavior in lampreys,” said Hamlett, who is currently an assistant professor of mathematics at Bucknell University.
The team began toying with different scenarios of spinal cord-injured lampreys—including both biologically plausible and implausible ones—all of which assumed no neural regeneration across the spinal cord lesion. That’s the utility of modeling, Hamlett said, “We can break things that you can’t break in biology.” The model took into account the curves and stretches created in the body above the lesion and transmitted that information to the rest of the body through the muscles, not the spine.
Even with a moderate amount of sensory feedback, the models show a surprising recovery of swimming patterns in biologically plausible models. Stronger emotional responses led to greater improvement.
Because lampreys have some of their neurons regenerated after injury and therefore have instructions descending from the brain to drive their movements, they may require less sensory feedback than the model. The team hopes to add neuronal regeneration to the model and examine how it affects movement and interacts with sensory feedback.
“If you have a good computational model, you can go through many more scenarios of manipulation than you can realistically with experiments,” Morgan said.
The team hopes that this study and future research will contribute to the treatment of spinal cord injuries and diseases that affect movement in humans. Brain machine interfaces and stimulation devices are beginning to incorporate the body’s sensory feedback to produce smooth movement after injury, and this research may inform the amount and response people need.
“You spontaneously (recover) an animal like a lamprey or a human who needs to be given a drug or an electrical stimulation device, get to the point where you have some things in the right place and then reuse what’s there. The same root of synaptic connections and growth. More should be achieved than trying to recreate the pattern,” Morgan said.
Christina Hamlett et al, Proprioceptive feedback amplification restores functional locomotion in a neuromechanical model of lampreys with spinal cord injury, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2213302120
Proceedings of the National Academy of Sciences