Scientists decode how the brain decides which memories to be saved for a lifetime

Most people know phrases like “photographic memory” or “elephant’s memory”, used for those who recall details exceptionally well. But the brain doesn’t store everything permanently.
Some memories fade within days or weeks, while others last years or a lifetime. What determines whether the brain forgets quickly or preserves a moment forever?
To find the answers to these questions, scientists from Rockefeller University in New York made mice perform a virtual reality activity, wherein the rodents were subjected to different environments.
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The mice formed strong, long-lasting memories for the environments that were shown to them several times, and quickly forgot the ones they were introduced to only a few times.
Published in the journal Nature, the study compares what happens in the brain when a memory lasts for a long time with what causes the organ to forget an event.
It says certain molecules in the brain regulate how memories are promoted or demoted, determining whether one remembers them forever or forgets them.
HOW MEMORIES ARE SHAPED
The scientists studied a brain circuit that connects the thalamus, deep in the centre of the organ, and parts of the cortex or the outer layer.
The study answers an important question: which molecular mechanisms promote important memories to the cortex and demote less important ones to be forgotten?
It found that there is no single on-off switch that controls memories, but several timed stages or molecular timers that turn on like a cascade over several weeks or days. In other words, it means long-term memory is a gradually evolving process, wherein brain regions reorganise the memories into long-lasting forms and make them more durable.
Scientists have identified three key molecules that decide how long a memory lasts. Two of them, CAMTA1 and TCF4, work in the thalamus, the brain region that helps with short-term memory and quick decisions. The third, ASH1L, works in the cortex, where long-term memories are stored.
CAMTA1 keeps a new memory alive for the first few days; without it, the memory fades quickly. TCF4 then takes over, strengthening links between brain regions, so the memory becomes steady over weeks. Finally, ASH1L makes the memory long-lasting. In simple terms, the thalamus chooses important memories and sends them to the cortex for lifelong storage.
Using correlation (variables change together), the scientists discovered which molecules are correlated with memory persistence.
To understand whether these molecules actually cause memories to last, rather than simply appearing alongside them, the researchers turned to CRISPR gene editing to remove each molecule one at a time in mice.
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When a molecule was knocked out, the mice forgot the repeated memory exactly at the stage when that molecule was normally supposed to act. When TCF4 was removed, memories faded because they could no longer be transferred from the thalamus to the cortex. A key discovery was that none of the three molecules are needed to form a memory, only to stabilise and maintain it.
The study shows that long-term memory is a step-by-step process, where important memories are passed along a timed chain of molecular “gates,” while unimportant ones drop out early.
These insights could guide Alzheimer’s research, especially because TCF4 and ASH1L appear crucial for long-term consolidation, potentially helping scientists design alternate pathways for memory transfer.
However, the study still cannot explain how these molecular timers are switched on or how the brain decides which memories matter, questions the researchers hope to explore next.
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