Light Workout: Optogenetics Stimulates Mouse Muscles

Light has been used to effectively stimulate muscle movement in mice optically, rather than electrically.

In a study involving bioengineered mice whose nerve-cell surfaces are coated with special light-sensitive proteins, researchers at Stanford University were able to use light to induce normal patterns of muscle contraction.

The new approach allows scientists to more accurately reproduce muscle firing order, making it a valuable research tool. The investigators, from Stanford’s schools of medicine and of engineering, 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.

Light delivered via fiber-optic cables causes a mouse's brain cells to fire.

The study, published online Sept. 26 in Nature Medicine, employed optogenetics technology, 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 (watch mouse movements being controlled in video embedded below).

“Our group’s focus is on restoring optimal movement for people with physical disabilities,” said one of the study’s two senior authors, Scott Delp, PhD, a professor of bioengineering and the Clark Professor in the School of Engineering. “With optical stimulation, we were able to reproduce the natural firing order of motor-nerve fibers — an important step forward.”

Optogenetics was invented at Stanford by the study’s other senior author, Karl Deisseroth, MD, PhD, associate professor of bioengineering and of psychiatry and behavioral science, 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,” Deisseroth said.

The peripheral nervous system includes the long nerve fibers that exit the spinal cord to innervate skeletal muscle, producing voluntary movement. Skeletal muscles work as aggregations of what physiologists call “motor units,” each consisting of a single nerve fiber plus the muscle fibers it innervates. At various points along the motor nerve, individual fibers exit the nerve to make contact with a variable number of skeletal-muscle fibers.

Motor units come in a variety of sizes. Small ones have single, thin nerve fibers that innervate several muscle fibers, whereas the lone, thicker nerve fiber in a larger motor unit may innervate several thousand of them. Normally, when motion is initiated, it takes stronger stimulation to “fire” thick nerve fibers than thin ones. Thus, the smaller, so-called “slow-twitch” muscle fibers start contracting before larger “fast-twitch” fibers.

Fast-twitch fibers are essential for powerful athletic motions such as running, but fatigue quickly as they burn through finite stores of their primary fuel, glycogen. Their more diminutive slow-twitch counterparts, which burn their fuel slowly, are crucial to delicate movements such as those involved in sewing or drawing, as well as for fine-tuning coarser, more powerful movements. Activities relying mainly on small slow-twitch fibers can proceed for long periods of time, while larger but more-fatigable fast-twitch fibers are reserved for brief bursts of high-powered activity.>