We've recently found that as in Aplysia, there is in the hippocampus, a homolog of the cytoplasmic polyadenylation binding protein – CPEB. There are four homologs which we creatively called one, two, three and four, and CPEB3 has a domain that has these glutamine rich residues, a prion-like domain. And it acts exactly like a prion. You put it into yeast, it forms aggregates. In the basal states, it's soluble, and it's a repressor of translation. With activity, it becomes aggregated, translocates to the ribosomes, and functions as a regulator of translation. And dopamine stimulates the aggregation, and initiates the protein synthesis. So it really fits in very much like serotonin did in Aplysia. So this was really very nice progress, and it encouraged us to begin to think a little bit more broadly about what can we do with this information.

Well one thing we could do is to try to explore disorders of memory storage. And we looked at a number of these. We began by looking at age-related memory loss. It had been thought for some time that there may be two independent processes in the brain,– Alzheimer's disease, and age-related memory loss. Now at first this was not appreciated, it part because until 1900 people didn't live very long. They lived to be 50 years old. So when I was in medical school in the 1950s, we were seeing, you know, people pretty much of that generation coming along, and Alzheimer's disease was not much discussed in medical school. But now, when people are living… men live to be 78, women live to be 82, you see a significant amount of age-related memory loss.

But people are not simply living longer, they're living better. So one sees in parallel with Alzheimer's disease, there appears to be a more benign process in which there is significant forgetting, but it doesn't seem to progress to other areas of knowledge, and it seems to be more restricted than Alzheimer's disease. So it doesn't interfere with speech, etc, etc or grammar formation and things like that. And so we thought we'd begin to explore it.