360 Video: Neuroscience Breakthroughs With Optical Lasers
We’re neurobiologists, so we study the brain. We are studying the brains of mice, and also small animals called hydra. The way we study the brain is with optical microscopes that use lasers—with these lasers, we can find out which neurons are firing in the brains of living animals.
You have probably seen brain scans from patients. In those brain scans, it’s a bird’s-eye view of the brain, or brain activity. So you have the whole brain in one picture. But you have to realize that every one of the pixels in those images has probably 50 to 100 thousand neurons. So with these lasers, we can actually see the individual neurons firing. That’s what the big deal is—that you can look into the brain of an animal and you can see the neural circuit firing away.
We’re doing this because we want to decipher the activity of the conversation that these neurons or having. We’re trying to break the code of the brain by trying to read out everything that these neurons are telling each other, and then hopefully decipher that at some point. And the reason we’re working with mice is because we’re interested in the human brain—in particular the cerebral cortex, the largest and most sophisticated part of the brain in humans. And it turns out that mice also have a cerebral cortex, so there’s some hope that if we can actually decipher the cerebral cortex of the mouse we’ll be able to use the same code, so to speak, to decipher humans.
For example, we just published two papers that are of direct medical relevance. In one of them, we studied mice that we engineered to have symptoms of schizophrenia. The way it works is, in humans, there’s this drug called angel dust, which you may have heard of. PCP. So it turns out that in addicts that take a lot of angel dust, they have schizophrenic attacks which are indistinguishable from schizophrenic patients. So if you shoot the person with a high dose of angel dust, you can turn that person into a schizophrenic just for a shore period of time.
We can do the same thing with mice. We can give them the exact same drugs. People that are interested in studying schizophrenia have been using this for a long time to generate what’s called a ‘mouse model’ of schizophrenia.
So in these mice, we used our lasers to look at the activity of neurons in the cerebral cortex. What we found is that it’s their patterns of firing that are abnormal. These patterns are kind of subtle, so unless you look at the activity of all the neurons, you would miss it—it’s a bit like a TV screen that has some static in the image.
So we’ve proposed, based on these results, that the problem with schizophrenia in humans is not that the neurons are abnormal, but that the way they fire together in groups is abnormal. And if this is the case, then it changes the view of schizophrenia, and this could lead to more effective treatment, because you could argue that people have been essentially looking at the wrong thing.
There’s another paper that we just published that has to do with epilepsy. Again using mice, which we injected with a substance that turns them epileptic, and we watched epilepsy spread through the cortex.
Epilepsy, if you can imagine, is like a fire that goes through a forest. And what we see is that when a mouse has different epileptic seizures, the way in which this activity propagates is exactly the same—it goes through the same cells in the same order every time. It’s very stereotypical, it’s very reliable.
And the other thing we found which was unexpected is that from one seizure to the next, the patterns changed in time—sometimes you’d have the seizure go through the brain in a second, and the next time it may take ten seconds—but it goes through exactly the same cells. It’s a bit like if you’re going from Boston to New York by car, and you always take I-95; sometimes there’s traffic and you take ten hours, and sometimes there’s no traffic and it takes three hours, but you always go through the same towns, one by one.
Actually, in the epilepsy field there’s been a huge debate, with some people saying epilepsy follows paths, like we see, and some people have said exactly the opposite, that every time you get a seizure it’s a completely random path. But no one has been able to measure these epileptic seizures with this instrument that lets us watch what happens cell by cell. So I think we found, in a way, the ultimate experiment to map how epilepsy spreads.
So those are two examples of clinical applications that directly come out of our work.
Explore one of Rafael Yuste’s laboratories in the 360 degree video below.