An alternative pathway for long-term memory formation

Researchers from the Max Planck Florida Institute for Neuroscience (MPFI) have discovered a new pathway for forming long-term memories in the brain, suggesting that they can form independently of short-term memories. Their study, which has been published in the journal Nature Neuroscience, offers exciting possibilities for understanding memory-related conditions.

Our brain works diligently to record our experiences into memories, creating representations of our daily events that stay with us for short time periods. Current scientific theories of memory formation suggest that short-term memories are stored in what we can imagine as a temporary art exhibition in our brain before being cleared out for representations of new experiences. A tiny fraction of these short-term memories — those most relevant to us — are moved to a more permanent exhibit, our long-term memory, where they are stored for days, years or decades. However, the MPFI team say there may be another route to long-term memory formation, akin to finding a secret pathway to a permanent gallery in the brain.

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

Mice prefer dark spaces and, when given a choice, will immediately enter a dark space from a brightly lit one. However, if a mouse is frightened in a particular dark space, the memory of the frightening experience will alter its behaviour and the mouse will avoid entering the dark space again. 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 space, suggesting they had no memory of the experience. The scientists had successfully blocked short-term memory formation.

What happened next was surprising to the research team. A day, week or even a month later, these mice were altering their behaviour to avoid where they were previously frightened. Mice that didn’t seem to remember the frightening experience an hour after it occurred showed clear evidence of remembering at later times. In other words, blocking short-term memory of the event did not disrupt long-term memory.

“We were initially quite surprised by this observation, as it was inconsistent with how we thought memories were formed,” said Dr Myung Eun Shin, the study’s lead author. “We didn’t think it was possible to have a long-term memory of an event without a short-term memory. However, when we repeated these experiments and used multiple tools and approaches to verify our findings, we were convinced.

“Rather than long-term memory formation being a linear process that requires short-term memory, a parallel pathway to long-term memory formation that bypasses short-term memory must exist,” Shin continued. The study has thus changed the model of how memories are formed in the brain, suggesting our brains are more resilient than previously thought.

“This new finding has revised our understanding,” said MPFI Scientific Director Dr Ryohei Yasuda. “We are now investigating how this newly discovered pathway to long-term memory formation occurs. We are excited to see what we can learn and what this could mean for preserving long-term memory retention, even when short-term memory is compromised by aging or cognitive impairment.”

Art by Helena Pinheiro