“We can activate or inactivate individual neurons or muscle cells, essentially turning the worm into a virtual biorobot.” Dr. Aravinthan D. T. Samuel, professor of physics at Harvard Center for Brain Science (Massachusetts, USA) is talking about optogenetics, one of the newest fields in science. The pioneer work was done around 2002. The name, optogenetics, was coined in 2006. It’s a kind of hybrid of science and technology, combining tweaking of genes to make cells light sensitive, and then using precisely focused laser light to affect those cells.
The point, at least so far, is not to create biorobots but to develop methods that make it possible to study the behavior of specific neurons (nerve cells) in living animals and now, while the animal is moving. This last capability is new, as two just-released research papers in the journal Nature Methods demonstrate:
One paper is from a collaboration of researchers at the Georgia Institute of Technology (USA) and the Johann Wolfgang Goethe University (Frankfurt, Germany) [Optogenetic manipulation of neural activity in freely moving Caenorhabditis elegans] and the other paper from a team at Harvard University, the University of Pennsylvania, and the University of Massachusetts Medical School that devised what they call CoLBeRT (Controlling Locomotion and Behavior in Real Time) system [Real-time multimodal optical control of neurons and muscles in freely behaving Caenorhabditis elegans].
The two approaches are quite similar, which may be unfortunate for the researchers, but it does illustrate that the work in optogenetics is intense and attracting attention.
C. elegans, as the worm in the studies is usually labeled, is one of the favorites in biology. It’s a simple creature, relatively, heavily studied and well documented. In the case of brain power it has exactly 302 neurons, which explains why it was picked for this kind of study. It’s genetics are also an open book, having been one of the first animals to have its genome sequenced.
Optogenetics begins with the genetics. The worm’s genetics are modified so that their neurons produce light activated proteins (with ungainly names such as channelrhodopsin-2, halorhodopsin, and Leptosphaeria maculans opsin) that either excite or inhibit neuron activity. How these proteins came to be identified is a long story, but they are indicative of the kind of detailed molecular work that is changing the way neuroscientists look at the functions of the nervous system.
Once the GM (genetically modified) worms are prepared, then the ‘opto’ (optics) comes into play. The two papers describe different technical approaches, but the essence is in the use of optics, mirrors, and precise mechanics to control the location of a specifically colored laser beam onto the worm. The trick here is that the worm is moving; it’s not some half-alive subject pinned to a Petri-dish. The other big technical innovation was devising a tracking system for the worm’s movement, running the input through a computer program, and converting the information into guidance for the laser beam.
By directing the light (usually blue or green) to specific neurons, the scientists were able to induce the worm to stop, go forward, turn left or right, and secrete eggs. Biorobot this is not, but it doesn’t take much imagination to see how this could be developed.
Of course, this is a very simple minded worm. Controlling vastly more complicated brains is many, many years down the research path. Nevertheless, this method is a useful tool to conduct experiments on neurological behavior at the level of single neurons. The hope is to improve and expand the techniques of optogenetics to get at long-standing questions in neuroscience.