Using optogenetics techniques, scientists from Max Planck Florida Institute of Neuroscience identified a new pathway for forming long-term memories in the brain. Their findings suggest that long-term memories can form independently of short-term ones, and open a door to new ways of understanding memory-related conditions and disorders. Full details are published in a new Nature Neuroscience paper titled, “Formation of long-term memory without short-term memory revealed by CaMKII inhibition.”
Some current scientific theories of memory formation suggest that memory formation occurs in a linear fashion. While most short-term memories are cleared to make room for new experiences, a small fraction are consolidated into long-term memories which can persist for days, years, or decades. But this new study suggests that the brain might have other ways of forming long-term memories.
It’s an important finding because “we now have strong evidence of at least two distinct pathways to memory function—one dedicated to short-term memories and another to long-term memories,” said Myung Eun Shin, PhD, the lead author on the study. “This could mean our brains are more resilient than previously thought.”
For their study, the research team deactivated CaMKII enzyme in neurons using an optogenetic technique that they developed previously. This particular enzyme is critical for short-term memory formation. Specifically, they targeted excitatory neurons in the mouse amygdala with an adeno-associated virus encoding an inhibitor for the enzyme.
They then ran experiments that exposed the mice to new experiences to test the effect of blocking CaMKII. In this case, they looked at what happened when mice were exposed to a frightening experience in dark spaces. Mice typically prefer dark spaces to brightly lit ones. But if they are frightened in a particular dark space, the memory of the experience will cause them to alter their behavior, and avoid re-entering the dark space again.
However, when the research team disrupted CaMKII’s activity, the results suggested that the mice did not remember their scary experience, even though it occurred just an hour earlier.
What happened next was surprising to the research team. A day, week, or even a month later, the mice were altering their behavior to avoid being in the place where they were previously frightened. In other words, blocking short-term memory of the event did not disrupt long-term memories of the event from forming.
“We were initially quite surprised by this observation, as it was inconsistent with how we thought memories were formed. 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,” Shin said. “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.”
Further research into this parallel pathway could lead to new insights into disorders where short-term memories are compromised by aging or cognitive disease.
