What is it about?

One of the most reliable ways to memorize something is to repeat it several times. It is usually assumed that each repetition of an event produces in the brain the same effect, and these effects gradually accumulate to form a long-term memory. Our work shows 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.

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Why is it important?

Сhanging the positions of the terms does not change the sum. So if a long-term memory is a sum of past experiences, it should not matter in what order the experiences were presented. We found, however, that the order of events is critical for the successful formation of memory. For example, when neurons were repeatedly stimulated at different levels of intensity, a long-term memory only formed if the intensity increased over time, but not when it decreased, even if the "sum total" of stimulation remained the same. This may represent a clever evolutionary adaptation. Events that escalate in intensity are more likely to be relevant in the future, and it stands to reason that neurons would prioritize forming memories in response to escalating patterns of stimuli over those that gradually wane. In fact, the molecular mechanisms behind this pattern sensitivity might be engaged in other contexts, such in cancer responses to various patterns of drug treatments. Our findings might therefore be relevant to fields beyond memory and learning.


Amongst other things, our study highlights the continued utility of non-traditional animal models, such as sea hares, to provide a diversity of perspectives in cell biology and neuroscience. Although much biomedical research is focused on rodents and other vertebrates closely related to humans, there is a lot we can learn from the rest of the animal kingdom.

Nikolay Kukushkin

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This page is a summary of: Precise timing of ERK phosphorylation/dephosphorylation determines the outcome of trial repetition during long-term memory formation, Proceedings of the National Academy of Sciences, September 2022, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2210478119.
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