Saturday, February 1, 2014

Light Mind Control: Sonic Screwdriver Required

by Joel Stevens

I am not a neuroscientist, far from it, even being a masters student in ecology I still get lost with the acronyms, the neurotransmitters and areas of the brain that all seem to sound like crazy aliens from Doctor Who. It's a complicated subject, anyone can see that, but what all of us in the scientific community and outside of it can agree on is that the recent breakthroughs in neuroscience are absolutely amazing!


When I hear of discoveries in neuroscience I get a massive wave of jealousy, thinking to myself how I wish I could be involved in the research. But of course once I read a scientific paper on the my own subject i'm reminded exactly why I went into Marine Ecology. Luckily for me, one of my best friends from my undergrad days is a lab tech in a neuroscience lab at Wayne State University, in Detroit Michigan. His lab primarily focuses on reward pathways associated with drug addiction. Since we are both on pretty opposite ends of the scientific community spectrum, me being a marine ecologist and he a neuroscientist, we tend to enlighten the other on the major advances in our respective fields. In 2010, he came over to my apartment after class extremely
excited about a recent technique a professor he was working with told him about. A technique some would call the first steps in mind control.

The technique is called optogenetics, now before you click back on your internet browser and watch another cat video, allow me a few minutes to blow your mind.

As the name would suggest this combines optics and genetics. What the name does not tell you is why this is such an incredible technique. To understand the magnitude of this i'll need to tell you a little science story; don't worry it's brief. In the 1970's microbiologists were looking at a certain algae, located in your friendly pond. Why? You may ask would one go to school for over a decade just to look at pond scum? Well my friends, what is curious about this algae is that it has a incredibly primitive eye. When I say primitive, I mean so primitive that is only able to detect light. Which these little guys use to orient themselves so they can swim towards the light and get the most bang for their photosynthesis.


Now you may find yourself asking, how is light part of mind control? Allow me to explain the importance. As most of us know, cells send messages through neurons using electrical signals. This is what occurs when the algae's ''eye'' senses light. The signals are caused by something called a membrane potential. Now, think back to your physics course in high school, remember the word potential energy? The concept is similar here, see our cells constantly pumping ions out of themselves and across their membrane. This causes more ions outside of the cell which then causes a membrane potential to form. Think of it as being in a crowded bar. I mean really crowded, to the point that you can't breath. Our cells and the algea set up a similar bar scenario with ions. Now imagine that their is a VIP area in which there is plenty of room to dance around. Naturally, you and your friends want to get a booth there to have a P. Diddy kind of night but you cant't because there is a big bouncer with a clipboard standing in your way. (These bouncers represent the voltage gated channels stopping the ions from passing.) Then to your surprise, he puts his hand to his ear piece and steps away from the gate! And now you and your friends are first in line, so what happens? You all rush in until the bouncer blocks the door again. After awhile people in the VIP area around you start having one to many and are then kicked out, representing the pumps that pump the ions. In doing so, this returns the party-goer ratio back to normal; overcrowded main area, comfortable VIP area or in the case of the algea and our neurons a reestablish gradient.

Now keep this idea in the back of your head as we continue. Scientists found that the algea's eye spot has protein channels along its surface, which when stimulated by light open up! Letting ions to rush in and a electrical signal to be generated. Thus allowing them to know where the light source is located. These proteins are called channelrhodopsins.

http://www.cobolt.se/Filer/bilder/opto1.png

Here's where it gets really cool! Like all proteins, there is a certain gene that codes for channelrhodopsin, which scientists located soon after they found the channel's existence. What they did next is pretty ridiculous. They were able to transplant the gene into one type of nerve cell in the brain of mice using a virus that implants the gene into the targeted cell. (Yes we can do that now!) So, now they have these transgenic mice with light sensitive ion channels in one type of neuron. What do you think would happen if they, oh I don't know, they placed a fiber optic cable in the skull of one of these mice and flipped it on? I'll tell you what would happen, all the cells that had channelrohdopsins would be simulated. In essence creating a form of mind control. All by using an extremely precise and quick method of stimulation, light!

I know what you're thinking, how is that mind control? In order to really appreciate this, it is important to understand that our brain is not made up of a single type of neuron. In fact it is made up of thousands maybe even hundreds of thousands of different types of neurons, most of which probably have extremely distinct functions. The firing of these neurons is what controls our brains, so it stands to reason if we control the neurons, we control the brain. Before optogenetics was developed there was really no way to single out one type of neuron, instead we could only knock out one area with a lesion or stimulate a certain region with electrodes. Which is great and all, except stimulating an entire area of the brain causes not only the group of neurons being targeted but also all the other neurons surrounding it to be stimulated. Now with this technique, optogenetics, we have the ability of singling out one type of neurons or even neural circuits! And the coolest thing is that unlike lesion studies where one would destroy a certain area and deduce the area's function, the use of light in optogenetics allows us to simply turn on one certain neuron and then turn it back off without damage, all in milliseconds!

Just check out this video to the right, by Karl Deisseroth at Stanford, one of people who pioneered optogenetics in the early 2000's.  They inserted light sensitive channels into the motor cortex of the mouse which controls movement.  As you can see when a blue light is turned on the mouse instantly starts running around in a circle! How crazy is that!?

It's absolutely incredible! And honestly a bit scary because this really is light controlling the brain.  Luckily, so far the advances using optogenetics have been on the good side, still waiting on the hypnotoad to show up and install fiber optic cables in our brains; Ah, maybe someday.

Now I should add, there is diversity of the channelrhodopsins. It turns out that not only can we insert channels that initiate action potentials with light, but we can also insert channels that inhibit electrical stimulation by causing ions to flow out of the cell. This could potentially be a new treatment in mental disorders that involve over-stimulation of areas of the brain, such as epilepsy. Which as of now treatment involves either prescription drugs, which bathe the entire brain in a single substance, or removing an entire area. Both of which can cause serious side effects. Similar research is being done for mental disorders such as schizophrenia, anxiety, drug addiction, and Parkinson's disease. Instead scientists could now use optogenetics to locate the area of the brain that is causing the seizures and shut down that area from propagating the stimulus to the other by simply shining light on the neurons. Kind of like a pacemaker for your brain. Mind control is pretty cool huh?

Now, actual clinical trials on humans are a bit further down the road, but the potential is definitely there for therapeutic benefits in the future. Presently, most research is focused on figuring out the exact neural circuits responsible for these mental disorders as well as more complex phenomena such as how our brains store and recall memories. For those of you that don't know a neural circuit is a collection of neurons that all coordinate together to perform a certain function. Mapping these circuits is believed to be the key to fully understanding how the brain functions overall. It is the key to connecting the dots from our knowledge of how single neurons interact with one another to form complex behavior.

Now it should be noted that optogenetics is not going to replace lesion studies or other methods any time soon, as it has and will continue to take a great deal of research to know all the function and paths of neurons in our phenomenally intricate brains. However, it still stands as an amazing technique that has great potential to advance our knowledge in a number of different areas within neuroscience. Many have come out in recent years and labeled it as a "fad", or that it's benefits have been drastically over-exaggerated. (See the blog entry by John Hogan, Why “Optogenetic” Methods for Manipulating Brains Don’t Light Me Up**. )Maybe the critics are right, maybe it will be quickly replaced, maybe the potential discoveries will fizzle out. Or maybe now. As for right now though let's just bask in the hype!.

For me, I believe that optogenetics will yield some incredible results. So sorry to all the critics out there, but I think in a few years time it's contribution to understanding the complexity of the mammalian brain will be extremely substantial. As I stated at the beginning of this blog, this is not my field, and my immediate knowledge of the possible implications of optogenetics is limited. That doesn't stop me from just taking a moment to just think about how incredible a discovery like this is. How amazing it is that we as a species have come to a point where we take proteins from a creature, such as pond algae, and transplant it into a mouse that we then control with a light source in real time! And if the starting age of mind control doesn't make you incredibly excited or a little unnerved, well then there are still plenty of cat videos left to watch on the internet

For more about optogenetics, check out this great TED talk by Ed Boyden of MIT.


References
Deisseroth, K. 2010. Optogenetics. Nature Methods, 8:26-29.

Tye, K. M., & K. Deisseroth 2012. Optogenetic investigation of neural circuits underlying brain disease in animal models. Nature Reviews Neuroscience 13:251-266.


Yizhar, O., L.E. Fenno, T.J. Davidson, M. Mogri, and K. Deisseroth. 2011. Optogenetics in neural systems. Neuron 71:9-34.

Video and Image Links

http://31.media.tumblr.com/2d5037f6a1c2b753aa18d06eb5f743a5/tumblr_mu28j8ifM01sw4g05o1_1280.jpg

http://king.uchc.edu/gallery/images/Chlamy_big.jpg

http://www.cobolt.se/Filer/bilder/opto1.png

http://www.youtube.com/watch?v=v7uRFVR9BPU

http://i.imgur.com/AMyPt1i.png

http://www.nature.com/nmeth/journal/v8/n1/images/nmeth.f.324-F2.jpg

http://www.youtube.com/watch?v=hupHAPF1fHY

1 comment:

  1. Interesting Topic! I wonder if they're would be a way for mice to train themselves to ignore the stimulus?

    ReplyDelete