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Exploring the mechanism behind habituation and dishabituation sensitization


Division for Neurobiology and Behavior
Eric Kandel Scientist
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I was very much influenced by Steve Kuffler. As I indicated before, he'd pulled together anatomy, physiology, and biochemistry into neurobiology, but he didn't have any behavior. So we called our group the Division for Neurobiology and Behavior.

And soon after I got there, Jimmy Schwartz was recruited to NYU. I had met him at summer school at Harvard when I went to take that chemistry course, he was with us in that house that we rented at 1588 Mass Avenue. And he had, after he graduated from medical school, he had gone to Rockefeller to get a PhD with Fritz Lipmann. And he was a very well trained biochemist. And as he was coming to NYU he was getting interested in the nervous system. So I showed him Aplysia, the big cells, and he realized this is wonderful. He could identify the transmitters involved in different identified cells. So we really had a wonderful little group that got going.

And I realized that now the big emphasis had to be in behavior, so Irving Kupfermann really pioneered… he defined a whole bunch of behaviors for Aplysia: feeding behavior, inking behavior, egg laying behavior, and simple withdrawal reflexes. He went on and actually identified that there were a group of cells called the bag cells attached to the abdominal ganglion, two clusters of cells that release a substance that was responsible for egg laying. Really quite fantastic. Wrote a very nice paper on that, but realized that many of those [behaviors] were too complicated for studying learning, and we focused on a very simple behavior, the withdrawal of the gill from tactile stimulation of the siphon, just like the withdrawal of a hand from a hot object. So Aplysia has a respiratory organ called the gill that is covered by a protective sheet of skin called the mantle shelf that has a residual shell that the opisthobranch mollusca have. And that mantle shelf ends in a fleshy spout called the siphon. If you apply tactile stimulus to the siphon, you get a brisk withdrawal of the gill.

So Irving worked on this behavior, and showed that it undergoes habituation and dishabituation. And then we recruited Vince Castellucci and Harold Pinsker who was also a very good behaviorist. And we began to study this in some detail. Irving and I worked out the neural circuit for the behavior. We showed that there were six motor neurons, there were about 20 odd sensory neurons and several interneurons. And we published a very nice paper in Science in 1969 indicating he'd been able to work out the neural circuit of a behavior in cellular terms. And a year later we published three papers in Science back-to-back which indicated that this behavior could be modified by learning - habituation, dishabituation - we could work out the sort of neural mechanisms, first on a sort of global level, and then the last paper on a cellular level, showing monosynaptic connections changing with habituation and sensitization. That just made a wonderful impact. Let me read you what we said in the last of those papers.

'The data indicate that habituation and dishabituation sensitization' - we had shown that in fact dishabituation is a form of sensitization - 'both involve a change in the functional effectiveness of previously existing excitatory connections. Thus at least in this simple case it seems unnecessary to explain the behavioral modifications by evoking electrical and chemical fields with unique statistical distribution in neural aggregates. The capability for behavioral modifications seemed to be built directly into the neural architecture of the behavioral reflex. Finally, these studies strengthen the assumption that a prerequisite for studying behavior modifications is the analysis of the wiring diagram underlying the behavior. We have indeed found that once the wiring diagram of the behavior is known, the analysis of its modification becomes greatly simplified. Thus although this analysis pertains only to relatively simple and short-term behavioral modifications, a similar approach may perhaps also be applied to more complex as well as longer-lasting learning processes.'

Eric Kandel (b. 1929) is an American neuropsychiatrist. He was a recipient of the 2000 Nobel Prize in Physiology or Medicine for his research on the physiological basis of memory storage in neurons. He shared the prize with Arvid Carlsson and Paul Greengard. Kandel, who had studied psychoanalysis, wanted to understand how memory works. His mentor, Harry Grundfest, said, 'If you want to understand the brain you're going to have to take a reductionist approach, one cell at a time.' Kandel then studied the neural system of the sea slug Aplysia californica, which has large nerve cells amenable to experimental manipulation and is a member of the simplest group of animals known to be capable of learning. Kandel is a professor of biochemistry and biophysics at the College of Physicians and Surgeons at Columbia University. He is also Senior Investigator in the Howard Hughes Medical Institute. He was the founding director of the Center for Neurobiology and Behavior, which is now the Department of Neuroscience at Columbia University. Kandel's popularized account chronicling his life and research, 'In Search of Memory: The Emergence of a New Science of Mind', was awarded the 2006 Los Angeles Times Book Award for Science and Technology.

Listeners: Christopher Sykes

Christopher Sykes is an independent documentary producer who has made a number of films about science and scientists for BBC TV, Channel Four, and PBS.

Tags: Aplysia, Stephen Kuffler, Irving Kupfermann

Duration: 5 minutes, 8 seconds

Date story recorded: June 2015

Date story went live: 04 May 2016