Controlling the brain, with lasers!

Adapted from a January 30, 2011 blog post

It's about time I started talking about what I actually work on! I'll have much more to say about my own specific projects later... but for today I'll just briefly highlight one of the most exciting techniques our lab uses: optogenetics. My neuroscience friends are already well-acquainted with this super-hot new technique. But for the uninitiated, allow me to introduce you to biology's latest & greatest fad!

Trendsetters

Recently, a study led by Lex Kravitz, a postdoctoral fellow in our lab, made waves in the news. (If you're interested, you can read the whole paper here.) It's one of the early works demonstrating the power of optogenetics in neuroscience. This technique, pioneered by Karl Deisseroth at Stanford University, utilizes light-sensitive proteins to control the activity of neurons with light. (see the diagram below for how it works)

In Lex's study, he and his co-workers targeted the gene for a light-sensitive protein to specific sets of neurons in mice, which allowed them to activate those specific cells using a fiberoptic inserted into the brain. The neurons they targeted are located in a major motor control circuit of the brain called the basal ganglia.

Within this circuit there are two main pathways -- one that stimulates movement and one that inhibits movement. In an elegant set of experiments, Lex and his colleagues demonstrated that by targeting one pathway or the other, they could cause the mice to run around or to freeze in place simply by turning on the laser. They then applied this technique to Parkinsonian mice and showed that activating the pro-motor pathway restores their movement to the level of normal, healthy mice.

And remember, all of this behavior was controlled entirely with lasers. If you go to the online version of this paper, you can watch cool videos of the mice responding to the light.

Why is it so super-hot?

The results of this study are exciting, but why is optogenetics SO hot right now?

The main answer lies in its specificity. In the past, fast control of neuronal activity was achieved almost exclusively with electrodes. This was done for brain cells in every type of situation -- in the laboratory dish, in animals, and even in humans (for example, deep brain simulation for Parkinson's patients).

The problem with sticking an electrode in the brain and zapping it with electricity is the lack of specificity. You're zapping EVERYTHING in that region. But the brain is a complicated structure, and even one tiny area can contain many different types of cells, with diverse and often opposing functions. An electrode will affect all of those cells and there's nothing you can really do about that.

In contrast, flashing light onto a brain area does absolutely nothing EXCEPT in the cells that you've specifically targeted to express a light-sensitive protein. Current methods for attaining specificity of expression are usually a mix of genetic techniques and site-specific injections into the brain.

Now it's possible for researchers to see exactly what certain types of neurons do. No more confounding effects of other intermingled cell populations. A variety of light-sensitive proteins have become available that can activate or silence neurons or even change signaling molecules within the cell. Optogenetics is not a panacea for every experimental difficulty in neuroscience, but I don't think I'm overstating if I say that it's revolutionizing the field.

Optogenetics is the new black

Within only a few years after development, optogenetic tools are quickly reaching labs everywhere and are being applied to countless areas of neuroscience research. Scientists have been able to address previously-unanswered questions about depression, learning & memory, sleep, perception, and much more. The techniques of optogenetics truly go with everything.

Lex's publication dealt specifically with Parkinson's disease, but the brain areas our lab studies are also involved in other movement disorders as well as Tourette's syndrome, obsessive compulsive disorder, schizophrenia, and addiction. Using light to precisely alter the activity of specific neurons in the brain not only increases our understanding of how the brain works but also opens doors for new therapeutic strategies in tackling diseases.

The fervor for optogenetics in neuroscience right now is pretty intense. The novelty and hype surrounding these techniques has sometimes been a quick ticket into high-impact journals. However, the field is quickly adapting and must soon reach a point where studies using optogenetics are appreciated purely for the quality of the science and importance of the questions that are addressed.

So yes, in time the hype and glitz of optogenetics will fade. But it's clear that this trend is here to stay.