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Marc Zimmer: Optogenetics: Three not-so-blind (anymore) mice

Thu, 07/19/2012 - 17:03 -- admin

The three blind mice are no longer blind. Well, the ones in the nursery rhyme may still be blind, but the other week researchers at the University of Southern California and the Massachusetts Institute of Technology used a scientific technique called optogenetics to restore the ability of blind mice to differentiate between light and dark. The mice had retinitis pigmentosa, a disease in which light-sensitive cells in the retina are destroyed, causing the brain to no longer receive visual image information.

Dr. Alan Horsager, of USC’s Institute for Genetic Medicine, and his team of neuroscientists injected a virus with the channelrhodopsin gene into light-insensitive cells on the surface of the retina. The modified cells could sense light and transmit the information to the appropriate section of the brain.

To test their sight, the mice were placed in a water maze with a light illuminating its exit. The blind mice randomly found the exit, while the sighted mice and the genetically modified mice were able to navigate the maze, proving their ability to distinguish light and dark.

Besides helping blind mice navigate water mazes (and saving them from farmer’s wife who cut off their tails with a carving knife) this technique could some day be used to help the more than 100,000 people in the U.S. who have lost their sight to retinitis pigmentosa.

This is a novel new use of optogenetics, an ever-growing and -evolving field. Until recently, neuroscientists would stimulate brain cells with electrodes, but even with the finest electrodes they could never activate single neurons. Now, thanks to optogenetics, scientists can use light and an algae protein to turn on individual neurons instantly.

In algae, the function of the protein channelrhodopsin is to let calcium ions enter the algae cells when they are exposed to blue light. In 2005, Karl Deisseroth, a professor in the departments of bioengineering and psychiatry at Stanford University, took the channelrhodopsin gene and inserted it into a single neuron of C. elegans, a worm often used in scientific studies.

To the same worm, he added the gene for halorhodopsin, a protein found in very primitive bacteria that thrive in salt flats, where the protein lets the chloride ion enter the bacterium upon exposure to yellow light. Negative chloride and positive calcium ions combine to neutralize each other.

The neuron in Deisseroth’s worm now had an on switch (blue light -> calcium ions) and an off switch (yellow light -> chloride ions). C. elegans has 302 neurons and their functions are well known, which let Deisseroth modify a neuron responsible for movement.

It worked: Blue light — the worm wiggled; yellow light it stopped. Now, no self-respecting neuroscientist is happy with controlling the negligible mind of a worm, and by 2010 Deisseroth and his group were using fiber optics to send mind-controlling blue and yellow light to the brains of mice, thereby manipulating their desire to run in circles.

Deisseroth and other optogenetists are not evil villains bent on controlling the minds of others. They have no nefarious master plans; they are more interested in using optogenetics and other techniques with fanciful names like brainbow to help us understand how the human mind actually works. They want to use optogenetic methods to manipulate defective neurons.

For example, optogenetics has already been used to return a normal gait to a mouse afflicted with Parkinson’s disease. Many may argue that controlling the heart is more important than controlling the mind. Optogenetics is up to that task, too, since it can be used to activate any cells. In November 2010, channelrhodopsin was expressed in mouse heart muscle cells, which responded to stimulation by blue light with a specificity never before observed with electric stimulation.

Optogenetics can be useful in all areas of medicine and biotechnology. In fact, Nature, the premier science journal, has declared optogenetics the most important technique of the future in these fields. Right now, scientists are making worms wiggle and blind mice see, but it won’t be long before these techniques are used on a much grander scale. The potential applications are mind-blowing.
 

Marc Zimmer is a professor of chemistry at Connecticut College and the author of “Glowing Genes: A Revolution in Biotechnology” (Prometheus 2005), the first popular science book on green fluorescent protein.

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