The Mysterious World of Long-Term Memories

The complexity of memory has been explored in our culture for centuries, and now modern science has shone a light on how long-term memories might be actually formed and destroyed.

Varda Lev-Ram of the University of California has been working with her team in order to understand how perineuronal nets, made up of proteins and carbohydrates, hold the key to understanding long-term memory.

Learning how these fragile net-like structures affect us could offer hope for people suffering from conditions such as Pathologic Memory Loss or Post Traumatic Stress Disorder. We talked with Varda in order to understand more about her exciting work.


Your work on long-term memories and perineuronal nets in the brain has garnered quite a bit of media attention in the last year. Can you elaborate on your findings?

Our recent hypothesis is that the code for life-long memory is in the holes in the perineuronal net. The perineuronal net (PNN) is created during the critical periods of each part of the brain and surrounds some neurons. The holes are like doors or windows in this structure that allow the formation of synapses. When the window is large the synaptic connection can be large and stronger and when the opening is small, only weaker synapses can form. When there is a strong neuronal activity that might lead to a lasting memory, a wall can be broken to enlarge a window or to create a new one. When rewriting our memories many thousand times during our lifetime there are bound to be errors, due to the rapid protein turn over inside cells. So basically our memories are fragile and vulnerable to their environment.

Evidence has suggested that destroying these PNN nets in some brain regions can reverse deeply ingrained behaviors. What are the implications of this?

The removal of memories via the PNN is an experiment that supports the hypothesis of the crucial role of PNN in memory storage. In the future it might be used to remove harmful memories such as those related to post-traumatic stress disorder. However, this is a rather dangerous and invasive approach since we do not have the knowledge of the precise location of memories, especially when they are complex and involve several parts of the brain.

I know scientists aren’t fond of speculating but I wondered what your thoughts were about ethical implications of altering memories. Movies like Inception popularized this premise but could we ever see a future similar to this? I’m aware of this strange breakthrough where scientists managed to implant a false memory into a mouse.

What we are mostly interested in is not memory alterations but rather understanding what makes it possible to remember things from childhood to deathbed. If we can figure out this mysterious question then maybe we can understand and help cure memory deficiency or pathologic memory loss. This might lead to figuring out how to alter memories that could be beneficial or unscrupulous depending how and whom will use it.

Where do you go now with your findings? And what does the future hold?

We are testing the hypothesis from different angels. We’re trying to work out the longevity of the PNN proteins and the correlation between densities of PNN engulfed neurons and areas that are known to hold long-term memory. Also we’re asking, does activity that involves learning and memory-creation induce a higher PNN protein turn-over? And are the holes in the PNN occupied by synapses? This is done by looking at three dimensional reconstructions of high resolution electron microscope images. And we’re looking at imaging changes in the PNN during neuronal activation in a memory-creating fashion. We hope to find out if PNN are really holding life-long memories as well as what exactly is happening when memories are lost and how we can prevent it.