Watching Neurons

To learn how brains think, we need to know more about neurons, or nerve cells in the brain. A scientist talks about new techniques to make movies of neurons growing inside the brains of living mice

Neurons are the nerve cells in the brain and spine that pass information back and forth.

If neurobiologists fully understood how neurons grow and change, it might help them treat diseases like Lou Gehrig’s Disease — or ALS . They’ve sampled neural tissue from different individuals. But according to Jeff Lichtman — a neurobiologist at Washington University in St. Louis — that’s like trying to learn the rules of football by comparing snapshots of different games.

Jeff Lichtman: Whereas, if you could just sit in the bleachers and turn on a movie camera and watch one football game, you probably could divine most of the detailed information about the game.

In 2000, Lichtman’s colleague Josh Sanes added a gene from jellyfish into mice that makes mice neurons light up green. Now Lichtman’s team is using special microscopes to make videos of growing, changing neurons in the brains of living mice.

Jeff Lichtman: And this has been just a revolution — it’s really the green revolution, if you will, because it gives us access to cells that are deep within tissue but now are glowing a particular color and since everything around them isn’t glowing except for those cells, you can really watch them.

Lichtman is currently studying how the connections between neurons — called synaptic circuits — change as animals mature.

We asked Dr. Lichtman what the next step was in his research for the next few months. He said there were two main areas. First, they would be looking at the earliest stages of nervous system development. In other words, they want to understand how the connections between neurons get pruned down as an animal matures. He says it’s anti-intuitive, but the adult has fewer connections between nerve cells than the fetus or infant. So they hope to look at the period before an animal is born.

The second research direction is looking specifically at disease. Lichtman says, “the NIH funds most of our work. It’s a powerful way to watch pathology develop in an animal — such as ALS or Lou Gherig’s disease — people have cloned the gene that causes the disease in humans and put it in mice. The mice die by five months (when they should be young adults) — they die of neuromuscular disease. We will follow the nerve muscle fibers over time to see what happens. Watching nerve cells regress from muscle fibers …” Lichtman says that his work is basic research. His goal isn’t to test possible treatments for disease, but rather to gain insight into disease and normal processes. In other words, he wants to know what ALS is and what it actually does to cells. Then, we’ll be closer to a cure.

We asked Dr. Lichtman why neurobiologists think it’s so important to understand how neurons grow and change over time. Lichtman said, “Yes, one of the great mysteris of the brain is what does physically change during learning? No one can find that difference. We hope that by following nevrous systems over time, we can get insights into what changes happen. Maybe you can prevent memory loss … We don’t know how information is stored in the brain. Can we find the underlying substrate by watching brains over time? Maybe this will be of practical use over time. It’s not with any particular idea that we know what the answer is and we’re tesing a hypothesis. We hope the animal will teach us, rather than use the animal as a testing bed for an idea.”

Excerpts from interview with Dr. Lichtman:

1) … and you do this for, you know, a few hundred years or a few thousand years until you actually have a picture of every single second of a football game and try to infer the rules of football. What would you learn if you did that?… .That in fact it doesn’t make much sense, because no two of those pictures were coming from the same football game… Whereas, if you could just sit in the bleachers and turn on a movie camera and watch one football game, you probably could divine most of the detailed information about the game –even by watching one game in completion.

2) And what has made that kind of work just become much easier — in many ways much more interesting — is that now we have mice in which the competitors are labeled different colors — so we have blue neuron fighting against a yellow neuron — and we can watch that fight and see exactly what’s happening.

What you have in your mind?