A paper in the April 1999 Nature Neuroscience coauthored by the assistant professor of neuroscience indicates that a protein called CREB may provide links to the past. Alberini's research is yet another step toward a clearer understanding of the foundation of memory; it could one day shed light on how the ability to remember disappears in people afflicted with Alzheimer's disease or amnesia.
CREB protein - the acronym stands for "cyclic AMP response element binding," which is itself a challenge to memory - is widely used throughout the evolutionary ladder. Various researchers have found the protein hard at work in the memory processes of mice, sea snails, and fruit flies, for example.
For the past ten years, scientists have been speculating on the CREB protein's role in consolidation, a term that describes a phase of long-term memory formation. "Consolidation is a short initial phase that occurs right after learning," Alberini says. "If it's disrupted in some way, then long-term memories are never formed. For instance, when humans have some kind of trauma, the events leading up to it might be remembered, but the trauma itself might be forgotten because consolidation fails to occur."
Alberini and M.D./Ph.D. student Stephen M. Taubenfeld suspected that CREB protein depends on certain consolidation-related genes from within the region of the brain known as the hippocampus (injuries to this area often result in amnesia). In collaboration with Professor of Neuroscience Mark F. Bear and postdoctoral research associate Kjesten A. Wiig, Alberini and Taubenfeld decided to compare CREB activity in a group of normal rats and others in which the fornix - a connection between the hippocampus and other brain structures - had been severed.
Using a test in which rats could choose between staying in a lighted box or moving into a darkened one in which they would receive an electric shock, the researchers discovered that animals with a severed fornix could not recall receiving the shock while normal animals had no difficulty remembering to stay in the light. When the researchers looked directly at the hippocampus, they found that normal animals averaged a 152 percent increase in CREB protein activation, but CREB levels in the forgetful animals were flat.
The results of these experiments pose new questions, says Alberini, but they also suggest more answers. "The message to make CREB protein and consolidate memories for long-term storage passes through the fornix," Alberini says, "so we know where this protein is acting." Next, she says, is figuring which genes the protein switches on.