Optogenetics used to effectively stimulate muscle movement in mice

WASHINGTON - Researchers have used a new technique-optogenetics-to stimulate muscle movement in mice whose nerve-cell surfaces are coated with special light-sensitive proteins.

The new approach allows scientists to more accurately reproduce muscle firing order, making it a valuable research tool.

Researchers at Stanford University employed a technology known as optogenetics, which involves the insertion of a specialized gene derived from algae into the genomes of experimental animals.

This gene encodes a light-sensitive protein that situates itself on nerve-cell surfaces.

Particular wavelengths of light can trigger nerve activity in animals endowed with these proteins, modifying nerve cells’ firing patterns at the experimenters’ will.

“Our group’s focus is on restoring optimal movement for people with physical disabilities,” Nature quoted one of the study authors, Scott Delp, as saying.

“With optical stimulation, we were able to reproduce the natural firing order of motor-nerve fibers - an important step forward,” he said.

Optogenetics was invented at Stanford by the study’s other senior author, Karl Deisseroth, who has used optogenetics in many experiments to conduct research on the central nervous system of freely moving animals.

“This marks the first time the technique has been applied to the mammalian peripheral nervous system,” said Deisseroth.

For the study, lead author Michael Llewellyn, of Delp’s lab, fashioned an “optical cuff” lined with tiny, inward-facing light-emitting diodes, which could be placed around the bioengineered animals’ sciatic nerves.

The LEDs emitted blue light at intensities high enough to penetrate deep into the nerve, ensuring that all of its constituent nerve fibres would receive adequate stimulation from brief impulses of light from the LEDs.

The investigators then showed that optical stimulation reproduced the proper firing order of muscle fibres, inducing contractions similar to those that take place under normal conditions.

Next, using various measures, the researchers compared optically induced muscle contractions with those induced by the electrical cuff. Small, slow-twitch muscle fibres were activated at the lowest levels of optical stimulation.

But with electrical stimulation, bigger fibres were triggered first. What’s more, optically triggered contractions were sustained far longer than those produced by electrical stimulation.

“With optical stimulation, the muscles retained about one-third of their initial maximum force after 20 minutes, and remained at that plateau for quite a while afterward,” said Llewellyn.

“Electrical stimulation completely exhausted the same muscles within four minutes,” he added.

Consistent with this, optical stimulation initiated contractions much more easily in muscles composed of predominantly slow-twitch fibres than in muscles richer in fast-twitch fibres. Electrical stimulation, in contrast, induced contractions equally in both muscle types.

The researchers also believe this technique could someday spawn practical applications, from restoring movement to limbs paralyzed by stroke or spinal-cord or brain injury to countering spasticity caused by cerebral palsy.

The findings were published in Nature Medicine. (ANI)