Tim Tully on Research Highlights: CREB’s Effect on Long Term Memory (2)
  Tim Tully     Biography    
Recorded: 01 Aug 2003

The basic experiment derived from earlier work that my lab and other labs in my field had been working on, that suggested that the cell signaling pathway called the cyclic AMP pathway was involved in learning and memory.

We also knew from work that was done in the first couple of years at Cold Spring Harbor Lab that if you gave flies repeated training sessions, if you allowed them to practice their association of an odor with footshock, they would, in fact, form a very lasting memory of an odor footshock association that would last a week or more which is as long as we measured it. Additional practice induced a long-term memory. In other animal models, the appearance of long-term memory was shown to be dependent of protein synthesis. So we had just finished experiments where we fed flies inhibitors of protein synthesis and showed that special long-term memory produced by additional training specifically was blocked in the presence of protein synthesis inhibitors.

Well, to a molecular biologist protein synthesis means gene regulation. And transcription factors regulate genes. And at that time, so now it’s in 1992, 1993, the only transcription factor that was known to be regulated by the cyclic AMP pathway was a transcription factor called CREB, which stands for cyclic AMP-response element binding protein. So it was logical, actually, for us to put two and two together and say, well, cyclic AMP is activated during memory formation. It communicates with a transcription factor called CREB, which regulates the expression of genes and subsequent protein synthesis. So the hypothesis we formed was that CREB was probably involved specifically in the appearance of long-term memory. If we were able to do a genetic disruption experiment of CREB, we would expect to see long-term memory blocked, but learning and early memory normal. It was a very specific hypothesis based on specifically what CREB did in neurons during this process of long-term memory formation.

Tim Tully is a molecular geneticist, interested in finding the genetic and biological basis of memory in order to better identify pharmacological and behavioral treatments for memory loss. In 1981, he received his Ph.D. from the University of Illinois. Tully joined the Cold Spring Harbor Laboratory staff in 1991 to work on discovering genes involved with memory. He became the St. Giles Foundation Professor of Neuroscience and led the Drosophila learning and memory program. In 1998 he founded Helicon Therapeutics, Inc., a development-stage biotechnology firm that works on new therapies for memory loss and other cognition disorders. In June, 2007, Tully left Cold Spring Harbor Laboratory to become Helicon's Acting Chief Scientific Officer, and assume a key role in the Michigan-based Dart Foundation as it expands its interest in funding neuroscience research.

His work on the transcriptional factor CREB gave way to the first experimental demonstration of enhanced memory formation in genetically engineered animals. Tully works to identify genes involved with long-term memory formation. Tully has determined that by the regulation of gene expression, new, long-term memories can be formed due to the growth of new synapses.