The parallel signaling pathway leaves long-term memory intact despite short-term disruption in mice

Using optogenetic techniques, scientists at the Max Planck Florida Institute of Neuroscience identified a new way to form long-term memories in the brain. Their findings suggest that long-term memories can form independently of short-term memories and open the door to new ways to understand memory-related conditions and disorders. All details will be published in a new one Natural neuroscience Paper entitled “Formation of long-term memory without short-term memory through CaMKII inhibition.”

Some current scientific theories of memory formation suggest that memory formation occurs linearly. While most short-term memories are erased to make room for new experiences, a small portion are consolidated into long-term memories that can last for days, years, or decades. However, this new study suggests that the brain may have other ways of forming long-term memories.

This is an important finding because “we now have strong evidence for at least two distinct pathways to memory function – one for short-term memory and one for long-term memory,” said Myung Eun Shin, PhD, the study’s lead author. “This could mean that our brains are more resilient than previously thought.”

For their study, the research team deactivated the CaMKII enzyme in neurons using a previously developed optogenetic technique. This special enzyme is crucial for the formation of short-term memory. Specifically, they targeted excitatory neurons in the mouse amygdala with an adeno-associated virus that encodes an inhibitor for the enzyme.

They then conducted experiments in which the mice were exposed to new experiences to test the effect of blocking CaMKII. In this case, her examined what happened when mice were subjected to a frightening experience in dark rooms. Mice usually prefer dark rooms to brightly lit ones. However, if they are afraid in a particular dark room, remembering the experience will cause them to change their behavior and avoid entering the dark room again.

However, when the research team interrupted the activity of CaMKII, the results suggested that the mice did not remember their scary experience, even though it had occurred just an hour earlier.

What happened next came as a surprise to the research team. A day, a week, or even a month later, the mice changed their behavior to avoid going to the place they were previously afraid of. In other words, blocking short-term memory of the event did not interfere with the formation of long-term memories of the event.

“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,” Shin said. “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.”

Further research into this parallel pathway could lead to new insights into disorders in which short-term memory is impaired by aging or cognitive disease.