I began to think of, you know, the need to work out a neural circuit, but also to ask the question, what might change in a neural circuit? And I began to read about ideas that people had about what could be the mechanisms of learning and memory that didn't reside in the cells per se.

Now, the first person to really think deeply about it was Ramón y Cajal who suggested the idea that learning involves changes in synaptic strength. This was elaborated later on by a guy who had a big influence on me called Jerzy Konorski, student of Pavlov, who developed the distinction between excitability and plasticity. He said when you stimulate nerve cells, they undergo two kinds of changes: transient changes in excitability, and more persistent changes in synaptic strength core plasticity. And people began to ask, well what sort of plastic changes are particularly effective? Well, one might just be activity, per se. Use, per se. And Eccles explored that and came to the conclusion that it was not very effective. And several other people, Delisle Burns also, came to that conclusion. So I began to wonder, what is it that might produce plastic changes that would be effective and could mediate learning?

The one possibility, what Ross Adie suggested, it's not in the synapses, it's in the extracellular field, but that seemed too weird for me. And it struck me that maybe it lies in the learning situation itself. Maybe learning uses, you know, different patterns of stimulation. So I read Kimble's revision of Hilgard and Marquis' classic text on conditioning and learning. I read some of Skinner's work. And I realized that simple forms of learning, like habituation, sensitization classical conditioning, involved different patterns of stimulation. Habituation involved repeated stimulation of one pathway. Sensitization involves the effect of one pathway on another. Classical conditioning involves contingent interaction between two pathways. And I said, my gosh, maybe that it's not use, but it's specific patterns of stimulation.

And what these psychologists, [Ivan] Pavlov and [Edward] Thorndike described, really stimulus paradigms for producing a behavior change. Well, those stimulus paradigms could be used as patterns of stimulation applied to nerves converging on single nerve cells. So I developed the idea, which I called analogues of learning in which you could record from a single cell, and stimulate a pathway repeatedly to simulate habituation. You could then stimulate a pathway occasionally, stimulate another pathway very strongly, and see whether or not you could simulate sensitization. And finally you could do the most magical experiment of all: pair them, boom boom, boom boom. See whether you can get classical conditioning.

And I wrote a grant to the NIH in 1962 to apply to work in Ladislav Tauc's laboratory in order to carry out those experiments. And I was funded. I got $10,000 for travel and living expenses that year abroad, which was very nice. And so it struck me as those two years were very rich years. And one of the things that was really critical for allowing me to think rather extensively about these problems in ways that influenced me for almost a decade thereafter was this argument I had with Denise about spending more time at home with Paul, not being so absolutely obsessed with the laboratory as I had been at the NIH. And that allowed me to spend more time at home, not only with Paul, but thinking and reading. And as someone once said about Jim Watson - I don't want to compare myself to him, but I like the metaphor - Jim Watson never confused hard work for hard thought. And I really spent a lot of time doing as hard thinking as I was capable of, and I enjoyed it, and I think it turned out to be very profitable for me.