New way to form long-term memories discovered

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Researchers at the Max Planck Florida Institute of Neuroscience have discovered a new way to form long-term memories in the brain. Their work suggests that long-term memory can form independently of short-term memory, a finding that opens exciting possibilities for understanding memory-related states.

A new perspective on memory formation

Our brains work diligently to record our experiences into memories, creating representations of our daily events that stay with us for short periods of time. Current scientific theories on memory formation suggest that short-term memories are stored in our brains in a kind of temporary art exhibition before being released to represent new experiences. A tiny fraction of these short-term memories – the ones that are most relevant to us – are moved to a more permanent display, our long-term memory, where they are stored for days, years or decades.

The most common theories assume that this is a linear process. Our experiences are encoded in a short-term memory, which is then consolidated into a long-term memory. A new study by Dr. Myung Eun Shin, Dr. Paula Parra-Beuno and the scientific director of the MPFI Dr. However, Ryohei Yasuda suggests that there may be another way to form long-term memory.

“This discovery is similar to finding a secret route to a permanent gallery in the brain,” said Dr. Shin, the lead author of the study. “The prevailing theory proposed a single pathway in which short-term memories are consolidated into long-term memories. However, we now have strong evidence for at least two different pathways to memory formation – one for short-term memory and one for long-term memory. This could mean that our brains are more resilient than previously thought.”

The most important finding: a disruption in the formation of short-term memory did not lead to a blockage of long-term memory

The research team focused on a specific enzyme in neurons called CaMKII, which is crucial for the formation of short-term memory. Previously, they developed an optogenetic approach that uses light to temporarily deactivate CaMKII. Using this tool, the team set out to block the formation of short-term memory in a mouse using light.

Mice prefer dark rooms and, if given the choice, will immediately enter a dark room from a brightly lit one. However, when a mouse is frightened in a particular dark room, the memory of the frightening experience changes its behavior and the mouse avoids re-entering the dark room. When the research team used their tool to disrupt memory formation, even those mice that had a frightening experience an hour earlier entered the dark room, suggesting they had no memory of the experience. The scientists succeeded in blocking the formation of short-term memory.

What happened next came as a surprise to the research team. A day, a week, or even a month later, these mice changed their behavior to avoid where they were previously afraid. Mice that appeared not to remember the frightening experience an hour after it occurred showed clear signs of remembering it at a later time. In other words, blocking short-term memory of the event did not affect long-term memory.

“We were initially quite surprised by this observation, as it was inconsistent with the way we thought memories were formed. We didn’t think it was possible to store an event long-term without short-term memory. However, when we repeated these experiments and used multiple tools and approaches to verify our results, we were convinced,” describes Dr. Shin. “Instead of long-term memory formation being a linear process that requires short-term memory, there must be a parallel path to long-term memory formation that bypasses short-term memory.”

Effects on memory impairment

This study has changed the model of how memories are formed in the brain. Significant scientific advances often only come about when previous models of understanding are overturned, and the team is excited to see where this line of research will take them. “This new insight has revised our understanding. We are now investigating how this newly discovered pathway to long-term memory formation works. “We are excited to see what we can learn and what this might mean for long-term memory retention, even when short-term memory is impaired by aging or cognitive impairment,” says Dr. Yasuda.

Reference: Shin ME, Parra-Bueno P, Yasuda R. Formation of long-term memory without short-term memory by CaMKII inhibition. Nat Neurosci. 2024. doi: 10.1038/s41593-024-01831-z

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