Sunday, October 10, 2010

Mind control for a good cause

Almost one year ago, I wrote a post on optogenetics, a new field that combines optical techniques (playing with light) and genetic techniques (playing with DNA) to study the brain. Optogenetics is an extremely powerful technique that can be used to control the activity of brain cells. So far, it’s been mostly researched as an experimental tool, but a recent study published in the journal Nature hints at the possibility of using this technique to learn how to treat the most common neurodegenerative disorder after Alzheimer’s disease: Parkinson’s.

Parkinson’s disease, a movement disorder, affects a part of the brain called the basal ganglia, which is critical for planning movement and selecting appropriate actions. The basal ganglia can be roughly divided into two pathways (or networks of brain cells): a “direct” pathway that facilitates (or enables) movement and an “indirect” pathway that inhibits (or prevents) movement. When someone has Parkinson’s disease, it is thought that their direct pathway is not active enough and that their indirect pathway is too active, and this leads to the muscle rigidity, tremors and slowing of physical movement.

In this study, the researchers used a virus to deliver a special channel to the brain cells of either the direct or the indirect pathway of the basal ganglia in mice. This may sound confusing at first, but it’s a really clever experiment. Here is how it works: when certain types of viruses infect cells, they incorporate their DNA into the DNA of the “host” cell, such that the host starts making virus DNA, and ultimately turns into a virus-making factory. The researchers essentially hijacked this process: they engineered a virus that contained the DNA for the special channel, and therefore, once the brain cells got infected, they started making the special channel. What’s so special about this channel? It is activated by light (hence the “opto” in “optogenetics”). When blue light hits this channel, it activates the brain cells.

To tease out the differences between the direct and the indirect pathways, the researchers divided their mice into three groups: a control group (no brain cells infected with the virus), a “direct” group (the virus targets the direct pathway, such that only cells in the direct pathway have the special channel), and an “indirect” group (the virus targets the indirect pathway, such that only cells in the indirect pathway have the special channel). By exploiting this technique, the researchers were able to activate either the direct pathway or the indirect pathway of the basal ganglia simply by shining blue light onto the brain of the mice.

(I realize this is all very complicated, but if you’re still with me at this point, congratulations on completing Optogenetics 101!)

And now for the results… *drumroll* As expected, when the direct pathway was activated, the mice moved more (they ran around more, stood up on their hind legs more, etc.). And when the indirect pathway was activated, the mice froze, and overall moved less. How’s this for mind control?

At this point, it’s easy to get carried away and imagine a plethora of crazy scenarios should this technology fall in the hands of the bad guys (“And now, you will dance for me! Gnahahaha!”) However, the researchers had good intentions. They went on to activate the direct pathway in a mouse model of Parkinson’s disease, and found that this procedure rescued the locomotion deficits of the mice. And that is a wicked finding.

Unfortunately, treating humans with optogenetics is not going to happen anytime soon. There are significant hurdles to overcome before we can even think about it: working with viruses in the brain, delivering the channels only where we want them, assessing unwanted effects, and so on. That said, this study elegantly confirms that somehow activating the basal ganglia’s direct pathway could be an important therapeutic target to treat Parkinson’s disease.

Reference: Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry. Kravitz AV et al. Nature, 466(7306):622-6 (2010).

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