Recorded: 01 Aug 2003
It has been reproduced in various other species in particular rodents and mammals. Other labs, like Eric Kandel’s, for instance, have been studying the cell biology of CREB in neurons at that level. And they’ve shown that the underlying cell biology of a neuron when it’s learning something new and forming a long-term memory is also controlled by CREB in a way that makes sense.
CREB is involved in a growth process that makes the connections between neurons stronger. That’s been shown to be enhanced when CREB is enhanced genetically in the aplysia model. So it really does look like CREB is acting as a control switch for when memory is induced and the effect of forming long-term memory is to grow a stronger connection between neurons.
So all of that has been shown. CREB has been studied now in various regions of the brain, including the cortex. It appears to be generally involved in this form of cellular plasticity that underlies memory formation. So the original observations from flies appear to be generally true, and evolutionarily conserved up into mammals, which is important for one of the other things that we have done.
Now in the meantime, if CREB is a transcription factor that means that it’s regulating the expression of other genes, other downstream genes, which presumably are the effectors that produce the growth at the connection between neurons which underlies the appearance of long term memory. My lab since 1994 [and] 1995 has been involved in two types of approaches to try to identify more of these downstream genes that are involved in forming a long-term memory. It’s taken a lot of people many years to make some progress in, but to date we have found sixty new genes by making memory mutants, screening behaviorally and then cloning the genes, and we’ve been using DNA microarrays to see changes in gene expression levels that result during memory formation in a normal fly. And there’s overlap between those two approaches which means that we found legitimate new downstream players involved in this process of growth and 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.