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Optogenetics: An On/Off switch for individual neurons

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 individual neurons on and off instantly. Some of the earliest work in optogenetics was done by Karl Deisseroth and Ed Boyden while they were working in Roger Tsien's lab. So it is not surprising that optogenetics can be viewed as an outgrowth of GFP technology and that fluorescent proteins are routinely used to show which neurons have been modified to become neural on/off switches.

In algae, the function of the protein channelrhodopsin is to allow calcium ions to 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 allows the chloride ion to 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 allowed Deisseroth to modify a neuron responsible for movement. It worked: blue light - the worm wiggled, yellow light it stopped, see cool uses (Boyden et al., 2005).

The On Switch
The "on" switch

In 2010 Nature Methods announced that Optogenetics was its method of the year.

Boyden, E. S., Zhang, F., Bamberg, E., Nagel, G. & Deisseroth, K. (2005) Millisecond-timescale, genetically targeted optical control of neural activity, Nature Neuroscience 8, 1263- 1268.

 


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