Scientists have been fascinated by the remarkable capacity of a jawless fish known as the lamprey to recover from spinal cord injuries for nearly 50 years. In spite of their sparse neural regeneration, lampreys may be able to swim once more thanks to a recent study.
A mathematical model was used by Christina Hamlet of Bucknell University and colleagues, including Jennifer R. Morgan of the Marine Biological Laboratory (MBL), to show how lampreys may use body-sensing feedback to regain swimming abilities after spinal injury. The research may lead to new therapeutic strategies for people or soft robot locomotion algorithms. Proceedings of the National Academy of Sciences is where the paper was published.
“The paper’s punchline is that even in the absence of descending command across that [spinal] lesion, you can boost the sensory feedback and restore locomotion,” said Morgan, an MBL Senior Scientist and Director of the MBL’s Eugene Bell Center for Regenerative Biology and Tissue Engineering.
“The paper’s punchline is that you can improve sensory feedback and restore movement even in the absence of descending command over that [spinal] lesion,”
Morgan, MBL Senior Scientist.
Lampreys recover quickly and almost completely, even after severe lesions deep within the spinal cord, unlike humans and other mammals. According to earlier research by Morgan, although neural regeneration does speed up recovery in lampreys, it doesn’t fully explain the situation. They must use another mechanism because only a small portion of the neurons and neuronal connections are recovered after a spinal cord injury.
“I was baffled as to how that could possibly operate. With just a few tiny, sparse connections, how could you create a nervous system that worked? Morgan questioned.
In addition to descending neural connections in the spinal cord, researchers had previously proposed that lampreys might also use body-sensing feedback, also known as proprioception or kinesthesia, to direct their movements. Eric Tytell, an associate professor of biology at Tufts University and a former MBL Whitman Center Investigator, was a former MBL Whitman Center Investigator whom Morgan had contacted to discuss this. Eric was already collaborating with Christina Hamlet, a co-mentored postdoc at Tulane University, and mathematics professor Lisa Fauci.
The most biologically plausible model of a spinal lesion in a lamprey demonstrates how it might recover its swimming ability by using kinesthesia (proprioception). Source: Christina Hamlet et al., PNAS, 2023, DOI: 10.1073/pnas.2213302120.
Tytell, Fauci, and Hamlet were simulating lamprey movement with mathematical models. Together, they sought to “see if we could model some of the effects of sensory feedback on swimming behavior in lampreys,” explained Hamlet, an assistant professor of mathematics at Bucknell University at the time.
The group started experimenting with various spinal injury lamprey scenarios that assumed no neural regeneration across the spinal cord lesion, including both biologically plausible and implausible ones. We can break things that you can’t break in biology, according to Hamlet, which is the benefit of modeling. The model sent information to the rest of the body through the muscles, not the spinal cord, and took into account the curves and stretching caused in the body above the lesion.
Even with a modest amount of sensory feedback, the models revealed a startling recovery of swimming patterns in the biologically plausible models. Even more improvement was seen with stronger sensory feedback.
Lampreys may require even less sensory feedback than the model because, following a lesion, some of their neurons do grow back. This allows them to use descending brain commands to drive movement. In order to test how neuronal regeneration affects movement and interacts with sensory feedback, the team plans to incorporate it into the model.
The number of manipulation scenarios that can be tested with a good computational model is much greater than what can be done through experimentation, according to Morgan.
The team hopes that this study and subsequent research will help develop treatments for people who have spinal injuries and movement-impairing illnesses. This research might help determine the kind and quantity of feedback that humans require as brain-machine interfaces and stimulator devices start to incorporate body-sensing feedback to create smoother movements after injury.
“Getting to the point where you have a few things in the right place and then reuse what’s already there should be more achievable than trying to recapitulate the identical original pattern of synaptic connections and growth,” said Morgan. “Whether you’re an animal like a lamprey that [recovers] spontaneously or a human that needs to be given a drug or an electrical stimulator device,”.
More information: Christina Hamlet et al, Proprioceptive feedback amplification restores effective locomotion in a neuromechanical model of lampreys with spinal injuries, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2213302120
