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A Conversation With Nobel Laureate and Neuroscientist Eric Kandel

March 28, 2006
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HAROLD VARMUS: Eric Kandel is a Nobel Prize winner in medicine and the university professor at Columbia University here in New York. He is one of the world's leading neuroscientists, and has dedicated his life to the study of the brain. His new book is called, "In Search of Memory: The Emergence of a New Science of Mind." It's both an autobiography and at the same time a history of the field of neuroscience.


ERIC KANDEL: ...The biology of the mind is a fabulous area. And let me just expand on that a little bit.

Obviously, we're very far from understanding higher mental processes, but even at this early stage one can see--and Columbia hopes to exploit that in what it calls the Mind/Brain Behavior Initiative--to what degree can the biology of mind unite the scientists to the humanities, C.P. Snow's great divide. And in certain areas, one can already see progress.

For example, you cannot be a practicing psychologist without asking interesting questions about behavior that ultimately must be related to the brain. And every good cognitive psychologist is in fact a neurobiologist right now. And I think those fields have not only come together, but will be one...

ERIC KANDEL: Nerve cells communicate with each other not randomly but at specific sites called synapses, from the Greek term "to clasp." And there had been a number of people, including Sherington and Cajal and Freud, who had said that learning is likely to involve changes in the strength of the communication between nerve cells. But when you are naive in the field and you move into it, you read lots of people. You don't know who has prophetic insight and who is just babbling.

HAROLD VARMUS: Of course, there was a debate about how that communication occurred.


HAROLD VARMUS: Whether it's electrical, chemical.

ERIC KANDEL: It's electrical or chemical. So, even that was just beginning to be resolved. And so, the first thing we did was to try to see whether we can figure out how sensory information comes into the hippocampus. It turns out the hippocampus represents very complex sensory information. And using single sensory stimuli, which we used, didn't get us anywhere. So I felt we had to take a completely new approach. ... So, I looked around at lots of experimental systems, lots of animals, and I looked at crayfish and lobsters and leeches. And I finally honed in on a marine snail Aplysia.

HAROLD VARMUS: Tell us a little bit about the snail.

ERIC KANDEL: It's a giant snail, about a foot in length. It gives out a brilliantly purple ink when you in any way threaten it. And its great attraction to me was the fact it has the largest nerve cells in the animal kingdom. Before I became presbyopic, I could see the cells with my naked eye.

Moreover, it became clear to me after working with it for a while, that not only were the cells gigantic, but they were so distinctive that you can give them names. You could call one Harold, the other one Eric, Connie, Denise. And you could come back to the same cell in every animal of the species. You can work out the communication pattern, how the cells talk to one another. You could work at how these cells relate to sensory and motor structures. You can work out a whole reflex.

HAROLD VARMUS: We don't think of a snail as having a particularly vivid memory life.... So, tell us about the equivalent of memory.

ERIC KANDEL: That's a very interesting question. It - it dawned on me -- and this is not original with me; people, the ethologists certainly had been aware of it -- That to learn and to remember is essential for survival.

You have to know where the food sources are and where the prey and the predators are, and they are likely to be in distinctive places and you want to be able to distinguish one place from another, distinguish them by appearance, et cetera. So, you have to learn these things and recall them. Much of life is acquired through experience, much of one's knowledge.

And so, it was clear that any process that is so important for an animal's survival is going to be retained in evolution. It's going to be conserved. And one trick all biologists know is that if evolution finds something that works, it holds on to it indefinitely. And I thought that if I found a mechanism of learning -- and there are lots -- there are going to be lots of mechanisms, but if I found a mechanism of learning in an animal, no matter how simple the animal, no matter how simple the task, it would ultimately lead me to ego and superego -- I'm joking -- it will ultimately lead me to an insight that would have general importance. There would be modifications, there would be frills; there will be extensions, but that the basic mechanisms might hold up. And I think by and large, this has been true.

HAROLD VARMUS: So, tell us about a memory event ... in the life of an Aplysia and how you studied it.

ERIC KANDEL: ...Aplysia can learn a number of things. For example... I first dissected -- worked out-- a very simple reflex in the animal. The animal has an external respiratory organ, like a lung. It's outside the body. It's called the gill. And it's normally protected by a sheet of skin. But in order to extract oxygen from the seawater, it usually is exposed. It is often exposed. And if you touch part of the overlying skin, you get a brisk retraction, both of this overlaying mantle shelf and of the gill, the respiratory organ. So you can modify the intensity of that reflex.

So I'm looking at variations in reflex intensity by three means. One is if you give a very weak touch, the gill will withdraw, because it expects something serious. But if the touch continues to be weak, it realizes this is boring and uninteresting and it stops responding to it.

That is a phenomenon that occurs in people; it's called habituation. You learn to ignore lots of stimuli at Sloane-Kettering because they distract you from the task. You can't survive at Columbia if you pay attention to all kinds of irrelevant stimuli. Academic life is a question of appropriate habituation.

And the inverse. If you get a noxious stimulus to the tail of the animal, you startle it. And now that same neutral stimulus that would produce just at best a modest reflex, would produce a more powerful reflex. That's called sensitization. And that's what I studied most extensively.

If you pair the neutral stimulus with the tail shock, you can actually produce classical conditioning, like Pavlov did.

So here I had in this absolutely simple animal three significant forms of learning, which I could characterize behaviorally and I could see--is this stored as memory? And you find that if you produce any of these procedures, one training trail, let's say, one stimulus or a few stimuli, the animal will remember it for a period of hours, then forgets and goes back to the basal state.

But in the snail, as in you and me, practice makes perfect. So if you repeat the training, the animal will remember this for days and weeks. And it turns out when you look into the nervous system, there are distinctive mechanisms for learning and short-term memory. They are very much related. But long-term memory is fundamentally different. And I've really spent, you know, the next 40 years exploring those differences.





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