Ted Abel in the lab, at that particular point, was beginning to take advantage of some of the methodology that Mark Mayford had introduced. Mark Mayford revolutionized the field of gene knockouts in the hippocampus. What we had used initially, what Susumu and I had used initially, were general knockouts in which the gene was knocked out in the whole animal. What Mark Mayford developed is using a CaM kinase promotor, he was able to produce knockouts that were forebrain-specific because that's the only place the CaM kinase promotor was expressed. Moreover he developed the tetracycline system for the brain whereby you could switch a gene on and off. So you not only had regional expression, but you had temporal expression.

And we now used this, Ted Abel used this, on PKA [protein kinase A]. Used a dominant negative inhibitor of PKA, and he found when you did that you interfered with the late phase of LTP, and you got rid of long-term memory. Really a very beautiful experiment in which he clearly identified a component of the late phase of LTP system and cyclic AMP. We were able to go on and show, together with Alcino Silva that CREB was important as a transcription factor.

So that was really sort of a major step forward in allowing us to understand how LTP functions a little bit more, and how it relates to memory storage. And that really inspired us to go one step further. What was really so wonderful about the hippocampus is one now understood that it had an important representation of space, and that was mediated by the place cells. And Cliff Kentros in my lab was interested in studying that, and we collaborated with Bob Muller from Downstate who was really one of the major people in studying place cells.

So I wanted to ask simple questions that the place cell people had never asked. You know, is the stability of place cells dependent on protein synthesis in the long run? We found that it was. We found that it was mediated by dopamine. And then we said, look, this is an unusual map. The visual system is a map, the… Wade Marshal had studied all of these maps, but these are built into the brain. The spatial map is very different. It's a cognitive map. So the capability to form a map is built into the brain, but the specific map, whether you're going to map this room, whether you're going to map next door, that is a learning experience. So presumably, you know, attentional processes must come in at least in the learning component.