Summary: The formation of long-term memory is based on internal neural learning processes and the repetition of events.

Source: NYU

Long-term memories depend on both the repetition of events and a complex neural learning process to make these memories last, according to a new study by a team of neuroscientists.

His findings provide a more detailed understanding of how these types of memories are formed and the perceptions that can disrupt their creation.

The leader of the study, New York University Nikolai V. “Repetition is a well-reported memory trigger—the more often something is repeated, the better it is remembered,” Kukushkin explains in the journal. Proceedings of the National Academy of Sciences (PNAS).

“But brain machinery is more complex than that. Our research shows that the effects of repeated events on individuals interact in complex ways and have different roles in forming long-term memories – not just neural repetition. ordering Repeated experiences and using that information to build memory can be used to differentiate between these events.

“For example, neurons can distinguish sequences of intensity and the difference between two similar events, which is only possible when the memory is increased over time,” he said.

The researchers, who included Thomas Kerr, a professor at NYU’s Neuroscience Center, and Tasnim Tabassum, a researcher at NYU, wanted to better understand what’s behind this well-documented neural process—specifically, how repeated events produce long-term memory when individual events fail to do so.

What is unclear is. why Repeated events connect to each other to form a memory.

To investigate this question, scientists have studied Aplysia californicaCalifornia marine sediments. Aplysia This type of research is part of the model because simple memories are well understood at the molecular and cellular level.

The neurons that control them can be isolated and studied in a petri dish, as the study authors did here, reproducing all the important parts of memory formation.

The researchers “trained” these neurons by applying repeated chemical pulses. AplysiaResponses to stimuli such as mild electric shocks are commonly used in experiments.

They then monitored the strengthening of long-term connections between neurons, thereby simulating long-term memory.

“Two-trial learning is by this method. AplysiaOr even marginalized Aplysia Neurons can be trained to form long-term memory after two experiences,” explained Kukushkin, a researcher at NYU’s Neuroscience Center and clinical assistant professor of liberal studies at NYU.

“Single trials have no effect, but two trials spaced out in time do.”

As part of these experiments, the researchers specifically examined the effect of the protein ERK, which is required for memory.

Previously, scientists thought that ERK activation should be built into the learning process. But in PNAS In the study, the researchers discovered a more complex dynamic: a “battle” between molecules that activate ERK (and therefore support memory) and those that disable it (and therefore oppose memory).

They recall that after one trial, the side that destroys the “tug of war” prevails and ERK activity is arrested. On the other hand, a second attempt is required for prevention Reduction In ERK activity, thereby allowing memories to be retained.

Scientists have used different variations of the training process: changes that affect memory depending on the style of the stimulus. By varying the amount of chemicals used to simulate electrical shocks, they improved the “intensity” of individual training sessions.

This shows the shape of the head
What is not clear is how repeated events interact with each other to form a memory. Image is in public domain.

When the two-trial training included events of varying strength, only the “weak-strong” training method produced long-term memory, whereas the reverse “strong-weak” sequence failed to do so. In other words, the same combination of tests has an effect only if it increases in intensity, but not if it does not decrease over time.

This may represent an evolutionary adaptation to prioritize memory for increasing stimuli, the scientists suggest—in other words, events that increase in intensity have more predictive power than those that decrease in intensity.

“Formation of long-term memory is therefore a tug-of-war of ERK over which of the two competing factions wins over time,” Kukushkin says.

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This shows the hands of an old woman

But perhaps more significantly, the work shows that the effects of repeated events do not simply accumulate. In fact, they have distinct roles, such as initiating and ensuring long-term memory commitment.

“Neurons not only repeat, but the ordering stimuli, and use that information to discriminate between different patterns of experience.

Financial support This research was supported by a grant from the National Institutes of Health (1R01MH120300-01A1).

So memory research news

Author: James Davitt
Source: NYU
Contact: James DeWitt – NYU
Image: The image is in the public domain.

Preliminary study: Closed access.
The exact timing of ERK phosphorylation/dephosphorylation determines the outcome of experimental repetition during the formation of long-term memory.By Nikolay V. Kukushkin et al. PNAS


The exact timing of ERK phosphorylation/dephosphorylation determines the outcome of experimental repetition during the formation of long-term memory.

Two-trial learning by Aplysia It shows unusual relationships between training trials where one trial has no effect but two correctly spaced trials produce long-term memory. Extracellular-regulated kinase (ERK) activity is important for intertrial interactions, but the mechanism remains unresolved.

A combination of immunohistochemical and optogenetic tools reveals the unexpected complexity of ERK signaling during the induction of long-term synaptic facilitation by two types of serotonin (5-hydroxytryptamine, 5HT). Specifically, dual ERK phosphorylation is accompanied by dephosphorylation of the active TxY motif at the pT site, leading to the accumulation of inactive singly phosphorylated pY-ERK.

Because phosphorylation and dephosphorylation occur simultaneously but differ in the amount of 5HT accumulation, mixed two-experiment protocols involving both “strong” and “weak” 5HT stimulation should be sensitive to the order and timing of experiments. Indeed, long-term synaptic facilitation is generated only when a weak pulse precedes it, not vice versa. This may represent a physiological mechanism for prioritizing the memory of escalating threats.

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