2003 Fifth Annual Beckman Scholars Symposium

"From genes to drugs for memory enhancement"

Tim Tully, Ph.D.
Professor of Neuroscience
Cold Springs Harbor Laboratory

Memory formation after olfactory learning in Drosophila displays behavioral and molecular properties similar to other species. Particularly, long-term memory requires CREB-dependent transcription, suggesting the regulation of "downstream" genes. At the cellular level, long-lasting synaptic plasticity also appears to depend on CREB-mediated gene transcription and subsequent structural and functional modification of relevant synapses. From a combination of DNA microarrays and a behavioral screen for new memory mutants, we recently have identified several genetic components of a molecular mechanism likely involved in synapse-specific modification during long-term memory formation. As with CREB, this novel pathway appears evolutionarily conserved. Based on this conservation, a high throughput drug screen was designed to identify small molecules that enhance CREB function in human cells. We have shown some of these compounds to be effective in enhancing memory in mice.

Tim Tully is the St. Giles Foundation Professor of Neuroscience at Cold Spring Harbor Laboratory, where he has conducted basic research on the molecular-genetics of memory for more than a decade, and is Founder and Acting Chief Scientific Officer of Helicon Therapeutics, Inc. Dr. Tully has worked on the genetic basis of memory his entire career. His seminal work on the transcriptional factor CREB, which yielded the first experimental demonstration of enhanced memory formation in genetically engineered animals, earned him a Decade of the Brain Award from the American Association of Neurology.