Proteins that are vital to long-term memory
September 16, 2013
These proteins send signals from the outside to the inside of a cell, inducing a cellular response that is crucial for normal functioning of the adult brain (and aspects of embryonic development, including stem cell differentiation).
“By removing the function of three proteins in the Wnt signaling pathway, we produced a deficit in long-term but not short-term memory,” said Ron Davis, chair of the TSRI Department of Neuroscience. “The pathway is clearly part of the conversion of short-term memory to the long-term stable form, which occurs through changes in gene expression.”
The findings stem from experiments probing the role of Wnt signaling components in olfactory memory formation in Drosophila, the common fruit fly—a widely used doppelgänger for human memory studies. In the new study, the scientists inactivated the expression of several Wnt signaling proteins in the mushroom bodies of adult flies—part of the fly brain that plays a role in learning and memory.
The resulting memory disruption, Davis said, suggests that Wnt signaling participates actively in the formation of long-term memory, rather than having some general, non-specific effect on behavior.
“What is interesting is that the molecular mechanisms of adult memory use the same processes that guide the early development of the organism, except that they are repurposed for memory formation,” he said. “One difference, however, is that during early development the signals are intrinsic, while in adults they require an outside stimulus to create a memory.”
Future prospects for therapeutics
“In this study, we discovered that three different proteins in what is known as the Wnt signaling pathway are required for the conversion of short-term memories to long-term memories,” Davis explained to KurzweilAI.
“This is important because this signaling pathway is conserved among many different organisms from flies to humans. Thus, our results offer not only an important insight into how the brain takes short-term memories and makes them into stable, long-term versions, but they could also lead to therapeutics to treat the many different types of memory disorders in humans.
“We still need to learn more, however, before taking this step. Although we know with precision the neurons in which the Wnt signaling takes place (mushroom body neurons), we do not yet know which neurons release the original protein (Wnt) in response to learning. This release is essentially the trigger that occurs at learning that activates the signaling pathway.
“We do not yet know the specific genes that change their expression patterns after learning. From ours and prior studies, it seems highly likely that the Wnt signaling pathway causes changes in the expression of genes, and that this is what makes the neurons different in their physiology when they are storing short-term memories, from when they become competent to store long-term memories.
“Once we have this information, we have a much better picture of the whole process and this could lead to identifying which proteins are the best targets for developing drugs that could aid in long-term memory formation.”
The study was supported by the National Institutes of Health.