Investigators in the lab of Dr. Karl Deisseroth, an assistant professor of bioengineering at Stanford, devised a clever way to take over functions of neurons:
To selectively take control of neurons, the researchers used a virus to insert genes for producing light-sensitive proteins into cells of interest. The gene ChR2 is derived from an algae that makes affected neurons more active when exposed to blue light. Deisseroth and collaborators first showed this in a paper in Nature Neuroscience in 2005. In this week’s paper, they demonstrate that another gene, NpHR, which is borrowed from a microbe called an archaebacterium, can make neurons less active in the presence of yellow light. Combined, the two genes can now make neurons obey pulses of light like drivers obey a traffic signal: Blue means “go” (emit a signal), and yellow means “stop” (don’t emit).
In the new paper, the group shows this technique can have immediately observable effects in living creatures. The Stanford team’s collaborators in Germany were able to cause tiny worms called C. elegans to stop swimming while their genetically altered motor neurons were exposed to pulses of yellow light focused through a microscope. In some experiments, exposure to blue light caused the worms to wiggle in ways they weren’t moving while unperturbed. When the lights were turned off, the worms resumed their normal behavior.
Meanwhile, in experiments in living brain tissues extracted from mice at Stanford, the researchers were able to use the technique to cause neurons to signal or stop on the millisecond timescale, just as they do naturally. Other experiments showed that cells appear to suffer no ill effects from exposure to the light. They resume their normal function once the exposure ends.
The most direct application of optical neuron control is to begin experimenting with neural circuits to determine why unhealthy ones fail and how healthy ones work.
In patients with Parkinson’s disease, for example, researchers have shown that electrical “deep brain stimulation” of cells can help patients, but they don’t know precisely why. By allowing researchers to selectively stimulate or dampen different neurons in the brain, the new Stanford technique could help in determining which particular neurons are benefiting from deep brain stimulation, Deisseroth says. That could lead to making the electrical treatment, which has some unwanted side effects, more targeted.
Another potential application is experimenting with simulating neural communications. Because neurons communicate by generating patterns of signals–sometimes on and sometimes off like the 0s and 1s of binary computer code–flashing blue and yellow lights in these patterns could compel neurons to emit messages that correspond to real neural instructions. In the future, this could allow researchers to test and tune sophisticated neuron behaviors. Much farther down the road, Deisseroth speculates, the ability to artificially stimulate neural signals, such as movement instructions, could allow doctors to bridge blockages in damaged spinal columns, perhaps restoring some function to the limbs of paralyzed patients.
Finally, the technique could be useful in teasing out the largely unknown functioning of healthy brains.