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Leg nerves activated by light offer new path to restoring mobility

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Leg nerves activated by light offer new path to restoring mobility

Optogenetic stimulation relies on nerves that have been genetically engineered to express light-sensitive algae proteins called opsins. These proteins control electrical signals such as nerve impulses — essentially, turning them on and off — when they are exposed to certain wavelengths of light.
Using mice and rats engineered to express these opsins in two key nerves of the leg, the researchers were able to control the up and down movement of the rodents’ ankle joint by switching on an LED that was either attached over the skin or implanted within the leg.
This is the first time that a “closed-loop” optogenetic system has been used to power a limb, the researchers said. Closed-loop systems change their stimulation in response to signals from the nerves they are activating, as opposed to “open-loop” systems that don’t respond to feedback from the body.
In the case of the rodents, different cues including the angle of the ankle joint and changes in the length of the muscle fibers were the feedback used to control the ankle’s motion. It’s a system, said Srinivasan, “that in real time observes and minimizes the error between what we want to happen and what’s really happening.”
Stroll versus sprint
Optogenetic stimulation also led to less fatigue during cyclic motion than electrical stimulation, in a way that surprised the research team. In electrical systems, large-diameter axons are activated first, along with their large and oxygen-hungry muscles, before moving on to smaller axons and muscles. Optogenetic stimulation works in the opposite way, stimulating smaller axons before moving on to bigger fibers.
“When you’re walking slowly, you’re only activating those small fibers, but when you run a sprint, you’re activating the big fibers,” explained Srinivasan. “Electrical stimulation activates the big fibers first, so it’s like you’re walking but you’re using all the energy it requires to do a sprint. It’s quickly fatiguing because you’re using way more horsepower than you need.”
The scientists also noticed another curious pattern in the light stimulated system that was unlike electrical systems. “When we kept doing these experiments, especially for extended periods of time, we saw this really interesting behavior,” Srinivasan said. “We’re used to seeing systems perform really well, and then fatigue over time. But here we saw it perform really well, and then it fatigued, but if we kept going for longer the system recovered and started performing well again.”
This unexpected rebound is related to how opsin activity cycles in the nerves, in a way that allows the full system to regenerate, the scientists concluded.
With less fatigue involved, the optogenetic system might be a good future fit for long-term motor operations such as robotic exoskeletons that allow some people with paralysis to walk, or as long-term rehabilitation tools for people with degenerative muscle diseases, Srinivasan suggested.

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