What reductionism allows you to do is to take a complex problem and focus on one component
of it and try to understand it in some detail.
And sometimes you can just do it by focusing on one component, other times it requires
selecting a particular biological system if you're working in biology, in which that component
is prominent or easy to study.
And that allows you to study in depth the problem.
It will be hard to do if you looked at it in all its complexities.
For me the reductionist approach was really very profitable and not something that I really
thought a lot about before.
I originally went to medical school with the idea of becoming a psychoanalyst.
I didn't have a strong biological background at all.
And then in my senior year at medical school there was a five-month elective period in
which you could do whatever you wanted to and I thought that even a psychoanalyst should
know something about the brain.
And so I took an elective in brain science.
There were very few people doing brain science in those days, but Columbia had an outstanding
person, Harry Grenfist.
And I worked in his lab and I worked with one of his associates Don Perpera and had
an absolutely spectacular experience.
I mean actually doing science is so different than reading about it.
There's a sensual pleasure of doing the experiments; there's the fun of thinking about it coming
up with a new finding.
I just thought it was marvelous.
And Denise and I had just decided to get married and we had dinner one night and I remember
saying to her, "You know, I could see doing this for the rest of my life but it's completely
unrealistic.
You don't have any money and I don't have any money, you know, we want to have kids;
I should have a really gone into practice."
And she banged on the table and she said, "Money is of no significance."
I should tell you sotto voce that in the subsequent 60 years she's not repeated those words very
often, but she did say them that night and it made a big impact on me.
So I decided to go ahead with science.
And when I got out of medical school, which she was in 1956, physicians were being drafted
in the service for two years, but if you qualified for the National Institute of Health that
served as an alternative to draft duty.
So he nominated me, Grenfist, to the NIH, National Institute of Health, and I was selected.
So in fact I spent three years there, I spent next three years doing brain biology.
And I asked myself what's the central problem in psychoanalysis and I thought memory storage.
We all who we are because we remember and psychoanalysis is designed to allow you to
relive earlier experiences, earlier memories in a protected environment.
Brenda Miller has shown that the hippocampus in the mammalian brain is central for memory
storage.
And I had mastered it in Grenfist's lab how to put electrodes into single cells.
This is something many people can do now, but when he taught it to me relatively few
people could do it, the fact the whole population doing brain science was very small.
So my colleague Olen Spence, whom I've recruited to join me on this and I were the first people
in the world to record from single cells in the hippocampus.
We were euphoric.
The people around us thought it was fantastic.
Two incompetent people coming to the NIH and the intellectual environment is so extraordinary
it brings them up to this higher level.
So we studied these single cells to characterize their properties and we saw after a while
they were not dramatically different from the other two or three groups of cells that
have been described.
So clearly learning doesn't reside just in the properties of cells, it should have been
obvious in the beginning, it resides in how behavior is modified by learning, how something
changes in the neural network.
And we had no idea what the sensor information coming into the hippocampus was.
We tried various things and nothing worked.
It turns out that space is very important, it's a complex modality.
So I realized one needed to take a very different approach, a reductionist approach rather than
going to the most complex example human memory, take it very simple.
Pablo Thorndike just studied simple reflex behaviors and how they were modified by learning.
So I began to look for an animal that had simple reflex behaviors and it was adventitious
from a nervous system point of view and that's what led me to Aplysia.
It's an animal that has only 20,000 nerve cells compared to the hundred millions of
nervous cells in your brain, it only has 20,000.
And each of them is gigantic.
Aplysia have the largest nerve cells in the animal kingdom.
And you can easily put an electrode into any of these cells and be there for 24 hours if
you wanted to.
And the cells are not only large they're uniquely identifiable so you can return to the same
cell in every animal of the species.
Not only that but it turns out that one of the most interesting laboratories, there are
only two laboratories working on it, was in Paris.
My wife is a Parisian chauvinist so we went to Paris.
The alternative was Marseilles, another person was working Angelique worked in Marseilles.
Denise said, "Going to Marseilles is likely going to Albany, we should go to Paris," so
we went to Paris.
We had a great year.
And I started to work out a very simple behavior in the animal, a withdrawal reflex like the
withdrawal of a hand from a hot object and I showed it could be modified by different
forms of learning.
And in each case the learning involved a change in the strength of synaptic connections.
So nerve cells connect with each other that junctions called synapses and I found that
those synapses, they're not fixed but they're plastic; they're modified by learning.
Certain kinds of learning causes an increase in strength, learned fear, classic conditioning.
Some like habituation learning to forget about something leads to a decrease in synaptic
strength.
Later I found there's a short-term memory node.
Long-term memory and - short-term memory is a change in functional connections that last
for minutes to hours and long-term memory is actually an anatomical change, a growth
of new synaptic connections.
So I really learned a great deal about this.
And then about 1980 I started a second front I returned to the hippocampus.
By that time one had a much better understanding.
And it turned out that the rules there were pretty much the same here except one is looking
at more complex behavior.