The molecular pathways involved in memory formation are beginning to unravel with a new key system discovered by Baylor College of Medicine in collaboration with UH.
A protein complex involved in a key cytoskeletal formation pathway, mTORC2, appears to have a prominent role in memory formation in both mice and fruit flies. BCM assistant professor of neuroscience Mauro Costa-Mattioli and BCM graduate student and first author in the study Wei Huang conducted this pathway analysis in mice while UH associate professor Gregg Roman did his research with flies.
“Mice, by themselves, are a single model and they give us a good glimpse but maybe not a complete glimpse of how memories form. It’s becoming more and more common that labs collaborate and look at different model systems, because each model system — in my case we study fruit flies, Drosophila melanogaster, in his case, mice — they each have their own benefit,” Roman said.
“By combining different model systems to see if we come up with the same answer, that gives us a great deal of confidence with that answer. One of things it tells us is that if it is the same in fruit flies as in mice that it’s been conserved over a very very long period of time.”
The key point, Roman said, is not only the discovery itself but its appearance in two distant relatives, implying that mTORC2 may have significant role in memory consolidation.
“It’s probably something very important. If it’s been conserved, if the same molecule in the same molecular systems have been used in fruit flies to consolidate memory as in mice to consolidate memory, it’s very likely that a lot of the species in between are using the same thing. And that also indicates that it is probably a very central feature of memory consolidation in the pathway that we uncovered,” Roman said.
To observe memory consolidation in fruit flies, Roman’s lab used negative feedback conditioning, associating a scent with an electric shock. They then placed the flies between two tubes, one containing the pain-related scent and another containing one unrelated to pain, allowing the flies to gravitate to either side, Roman said.
The flies without a functioning pathway did not have as much of a preference for either side as the ones that did contain the cytoskeletal-forming pathway. What Costa-Mattioli’s team did next was expose its mice to a drug that would supplement the missing components of the knocked down pathway.
“In mice, what Mauro was able to do is he was able to show that if you gave a drug that bypassed the defect in mTORC2, that those mice were now able to learn,” Roman said. “We are looking to see if we can have these ‘cognitive enhancer drugs.’”
“If you identify molecular pathways that are required for the formation of long-term memory, you can then potentially target these to help enhance the formation of memories.”
Looking toward the future, Roman said that with more time and research, these memory enhancers might be available to help relieve some of the symptoms of aging, such as memory decay.
“There are reasons why young people might want to increase their memory, but also it’s a very serious problem for the aging population where you have age-related memory decay and decline,” he said.
“What we can do, as we understand and develop more of these cognitive enhances, we can perhaps develop cocktails that can help in situations where memory declines to help give them boosts and maintain a higher level of cognitive performance later and later in life.”
