Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Light workout: Stanford scientists use optogenetics to effectively stimulate muscle movement in mice

27.09.2010
Researchers at Stanford University were able to use light to induce normal patterns of muscle contraction, in a study involving bioengineered 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. 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.

The study, to be published online Sept. 26 in Nature Medicine, 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," 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.

Previous attempts to restore lost motor function using programmed sequences of electrical impulses, delivered via a cuff placed around a nerve, have enabled paralyzed people to walk, if only for a few minutes. Unfortunately, large nerve fibers are more responsive than smaller ones to electrical stimulation, so muscles contract in the wrong order - large, fast-twitch fibers first, then small, slow-twitch ones; this results in jerky motion and, soon thereafter, fatigue.

For the Nature Medicine study, lead author Michael Llewellyn, PhD, 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 fibers 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 fibers, 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 fibers were activated at the lowest levels of optical stimulation. But with electrical stimulation, bigger fibers 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, who is now finishing his work on an MD at Stanford. "Electrical stimulation completely exhausted the same muscles within four minutes." Consistent with this, optical stimulation initiated contractions much more easily in muscles composed of predominantly slow-twitch fibers than in muscles richer in fast-twitch fibers. Electrical stimulation, in contrast, induced contractions equally in both muscle types.

The approach is, for now, primarily a research tool, Delp said. But it holds promise for clinical applications in the longer term if a way can be found to safely introduce genes coding for light-sensitive nerve-cell-surface proteins into people, he said. Just as techniques now use electrical cuffs to get paraplegics to walk for a few minutes, optical cuffs could be inserted microsurgically at appropriate places along motor nerve bundles, so that computer algorithm-controlled light impulses could induce firing in different fibers at different times, mimicking natural physiology.

Delp and Deisseroth are conducting similar research with a different protein that, in response to light, inhibits nerve fibers instead of triggering impulses in them, in the hope of someday being able to control spasticity, as for example occurs in cerebral palsy.

The study's other co-author is Kimberly Thomson, PhD, a postdoctoral scholar in Deisseroth's laboratory. The study drew funding from the National Institutes of Health and Bio-X, an interdisciplinary consortium at Stanford.

More information about Stanford's Department of Bioengineering, which also supported the research, is available at http://bioengineering.stanford.edu/. The department is jointly operated by the Schools of Medicine and of Engineering.

The Stanford University School of Medicine consistently ranks among the nation's top medical schools, integrating research, medical education, patient care and community service. For more news about the school, please visit http://mednews.stanford.edu. The medical school is part of Stanford Medicine, which includes Stanford Hospital & Clinics and Lucile Packard Children's Hospital. For information about all three, please visit http://stanfordmedicine.org/about/news.html.

Bruce Goldman | EurekAlert!
Further information:
http://www.stanford.edu

More articles from Life Sciences:

nachricht Researchers develop eco-friendly, 4-in-1 catalyst
25.04.2017 | Brown University

nachricht Transfecting cells gently – the LZH presents a GNOME prototype at the Labvolution 2017
25.04.2017 | Laser Zentrum Hannover e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

NASA's Fermi catches gamma-ray flashes from tropical storms

25.04.2017 | Physics and Astronomy

Researchers invent process to make sustainable rubber, plastics

25.04.2017 | Materials Sciences

Transfecting cells gently – the LZH presents a GNOME prototype at the Labvolution 2017

25.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>