How do some memories last a lifetime? NYU scientists discover key process to long-term memory formation

The repetition of events, data, and information is key to forming long-term memories, but not the only key. A new study conducted at New York University reveals an additional, complex neurologic process that’s essential to the formation of long-lasting memories.

Scientists explain that their findings contribute to understanding disruption of memory formation. The study was led by Nikolay V. Kukushkin, a researcher at NYU’s Center for Neural Science and a clinical assistant professor in Liberal Studies at NYU.

“Repetition is a well-documented trigger for memory formation—the more times something is repeated, the better it is remembered,” Kukushkin explains in a statement. “However, the brain’s machinery is more complicated than that. Our research shows that the effects of individual repeated events interact in more nuanced ways and have distinct roles in working to form long-term memories—neurons can sense not just repetition, but also the order of repeated experiences and can use that information to discriminate between different patterns of these events in building memories.” 

Kukushkin continues: “For example, neurons can tell the difference between two events in escalating order of intensity and those same two events in the opposite order, forming a memory only if the intensity increases over time.” 

What has been unclear is how repeated events interact with one another to form a memory.

The scientists studied Aplysia californica, the California sea slug, to address their question. They used Aplysia for this research because its memory formation is understood at both cellular and molecular. Individual neurons (nerve cells) can be studied in a Petri dish. The researchers applied repeated chemical pulses that reproduced Aplysia’s responses to stimuli.

Next, they monitored the long-term strengthening of connections between the neurons, which mimics the formation of a long-term memory. Specifically, the scientists studied, with particular interest, the activity of the protein ERK, which is required for memory formation.

They used a two-trial technique.

Aplysia, or even isolated Aplysia neurons, can be made to form a long-term memory after two experiences,” explains Kukushkin, “Single trials have no effect, but two trials, if they are appropriately spaced in time, do.”

It was expected that ERK activation would build up during the learning process. In this study, however, a more complicated dynamic was discovered. The team described it as a “tug of war” between molecules that activate ERK and molecules that deactivate the protein – favoring memory formation versus suppressing memory formation.

After a single trial, the deactivating side of the “tug of war” was winning, deactivating ERK, which suppressed formation of memories. A second trial, however, prevented the decrease in ERK activity, which favored acquisition of memories.

“Long-term memory formation, then, depends on which of the two competing sides of the ERK tug of war wins over time,” explains Kukushkin. “But perhaps more significantly, the work demonstrates that effects of repeated events do not simply accumulate. In fact, they have distinct roles, such as to initiate and confirm the commitment of information to long-term memory. Neurons can sense not just repetition, but the order of stimuli, and they use that information to discriminate between different patterns of experience.”

This study appears in the journal Proceedings of the National Academy of Sciences (PNAS).

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About the Author

Dr. Faith Coleman

Faith A. Coleman MD
Dr. Coleman is a graduate of the University of New Mexico School of Medicine and holds a BA in journalism from UNM. She completed her family practice residency at Wm. Beaumont Hospital, Troy and Royal Oak, MI, consistently ranked among the United States Top 100 Hospitals by US News and World Report. Dr. Coleman writes on health, medicine, family, and parenting for online information services and educational materials for health care providers.

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