The Temporal Choreography of Memory

The hiatus on this blog was a combination of taking the GREs and pre-holiday laziness. I am, however, pleased to announce that this post and the previous one are results of my original interviews with researchers who were kind enough to give me their time and assistance.

Precious as our memories are, they are also our most fragile possessions; study after study has shown that they erode over time. This impermanence is controlled by a staggeringly complex process that neuroscientists have long been trying to comprehend. Now, researchers from New York University and the University of California, Irvine, have published research in the Proceedings of the National Academy of Sciences that uncovers a major clue to this process. They identify specific molecules that shape not only how, but where and when memories are created. Specifically, they found that two, MAPK and PKA, interact spatially and temporally in our neurons to trigger memory formation.

Team leader Dr. Thomas Carew from New York University calls this molecular interaction a kind of “temporal choreography”. His team used neurons from Aplysia californica, the California sea slug, to observe the interactions of MAPK and PKA. Humble though they may seem, sea slugs are a boon to memory research. Compared to the neurons in the human brain, which number in the order of trillions, Aplysia has about 10,000 neurons, each of which are much larger than ours, making their molecular pathways easier to study.

By stimulating the neurons in the tail of the sea slugs, the team was able to monitor when and where MAPK and PKA appeared to consolidate the memory of that stimulation. They found that PKA is crucial for both short term memory, which lasts over a single trial, and intermediate-term memory, which lasts a few hours. Long term-memory, which forms over a few days, required both MAPK and PKA. Ultimately, “we also found that MAPK’s actions are required for PKA to work,” says Dr. Carew. Even more interestingly, PKA was detected first in the synapses of neurons and then in the cell bodies, providing an important clue to both where and when memories are formed.

“MAPK and PKA are both important and we’ve known that for a while,” says Dr. Todd Sacktor, who published seminal work on how the PKMZeta protein helps create and even restore long-term memories. “How they interacted, however, was a mystery. What we especially didn’t know was whether they interacted in series, or parallel. But now through this study, we realize that they act in series in the synapse.” In terms of highlighting how the brain learns, Dr. Sacktor thinks this is “a big advance”.

Although the interactions of these two molecules helps us understand how neurons create memories, Dr. Carew acknowledges that much needs to be done to bring this research to the clinic or bedside. “We can’t just drink a quart of PKA and learn to speak Greek,” he says. The next step would be to test the behaviors of sea slugs with this model of memory formation in mind. Although the behavioral constraints of Aplysia are significant — “Let’s say they’re not getting into NYU or Yale”, is Dr. Carew’s assessment — they can be used to study the molecular level of memory creation.

Dr. Sacktor thinks the study may have even more immediate implications. “There’s been an awful lot of effort done by different labs in using PKA for cognitive enhancement,” he explains. “This study would provide them with clues on what the best way to deploy those PKA enhancers would be.”

Despite the building body of work in memory formation and retention, Dr. Carew does not believe that a silver bullet exists for memory-related diseases like Alzheimer’s or dementia. “Not all cognitive impairment is the same; the deficit in memory might look the same, but there are very different underlying mechanisms,” he explains. Instead, Dr. Carew suggests that our increasing understanding of the memory pathways will lead to targeted therapy for these ailments — and hopefully, the reduction of human suffering.

My thanks to Dr. Carew’s wonderful explanations and the press office of NYU for helping me get in touch with him. Thanks also to Dr. Sacktor, who was kind enough to give me some time on a weekend to discuss this work. 

References: 

1. The original press release by NYU on EurekAlert: http://www.nyu.edu/about/news-publications/news/2012/10/15/neuroscientists-find-the-molecular-when-and-where-of-memory-formation.html

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