Sick Kids Researchers May Have Finally Figured Out Why We Can Remember Multiple Memories at Once

Have you ever noticed when you remember something from your past, you may also recall other moments from that time. It seems to be even more pronounced when remembering a moving event, such as the assassination of President John F. Kennedy, the demise of the space shuttle Challenger, and more recently, the tragic events of 9/11.
While many of us experience these multiple memories, the mechanism behind their formation has been a biological enigma. For over a century researchers have tried to figure out how these combinations – or co-allocations – of memories occur. Yet successes have been few and far between.

The first description of multiple memories came in 1908.Back then, the evolutionary biologist Richard Semon called the phenomenon an engram. He defined it as an “enduring though primarily latent modification in the irritable substance produced by a stimulus.” Essentially, particular events could somehow activate the brain such that a collection of memories could be formed. Unfortunately, finding out exactly how engrams were made was not within his abilities.
Over the years, the engram has been the subject of significant investigation and numerous theories regarding their formation have been made. The most popular suggest an engram is formed by a collection of neurons that activate in a coordinated fashion to recall certain closely timed events. Yet rarely has there been a defined mechanism to explain how this happens.
But now there may be an answer as to how multiple memories seem to co-allocate. The results come from a recent study by a group of researchers at the Hospital for Sick Children in Toronto led by Dr. Sheena Josselyn and Dr. Paul Frankland. Based on their work in mice, published in the journal Science the basis for multiple memories may be related to the time at which they are experienced.
Much like many famous memory-causing events – such as assassinations, natural disasters, and acts of terror – the group used fear to invoke engrams. Two different types of stimulus were used so the reactions could be interpreted separately. As for the moments of fear, they were separated over time to determine if they could be co-allocated.
The first experiments wanted to show the potential for memory co-allocation. The team separated the fear stimuli by either six hours or twenty-four hours. As they expected, the memory of the second event was enhanced after the six hour interval yet not after twenty-four hours. In addition, that enhancement only occurred if the mouse actually felt fear after the first event. This provided some evidence to explain why we seem to recall several memories at the same time as a major occurrence.
With the first stage complete, the team then went further into the brain to identify the mechanism behind this co-allocation. In these experiments, the group focused on the presence of a particular protein known to be involved in memory. It’s called the cyclic adenosine monophosphate/calcium ion-response element binding protein. Yet most know it simply as CREB.
For years, Josselyn’s group has known CREB plays a significant role in the development of memories in a section of the brain known as the lateral amygdala. The levels of CREB in combination with the excitability of a neuron dictate whether it will be allocated into a memory. If this sounds like a competition, it is. Only those neurons with the highest functionality at the moment of the stimulus will be allowed to hold the memory.
The team wanted to show the same rules applied for co-allocation of memories. For excitability, the group used optogenetics. Neurons in the lateral amygdala were changed genetically such that blue light would excite them while red light would inhibit them. As expected, excitation led to memory allocation while inhibition prevented the process.
To test CREB, a virus was used to infect cells and either increase or reduce the levels of this protein. Again, higher levels led to memory while a lack of the molecule ended up in less recall ability. These results had no dependence on time as they were artificially manipulated.
While the team proved the chemical basis for the formation of multiple memories, they still were not sure how the neurons connected such that they formed a proper engram. Amid the massive number of neurons within the lateral amygdala, hundreds would presumably be ready to allocate memories. Yet, not all of them did. There were winners and losers in the competition. There had to be a controller akin to a gatekeeper working to guide the formation of these multiple memories.
Based on the anatomy of the lateral amygdala the best candidate happened to be a group of cells known as gamma-aminobutyric-acid–releasing parvalbumin interneurons, but most call them PV interneurons. Despite the long name, these cells have a simple task: inhibit widespread signalling. When the team examined these cells, they were highly active around losers within the first six hours after the initial fear event. After twenty-four hours, however, the PV cells were quiet. In the same way, if the PV cells were inhibited, those losers were still able to acquire memories.
The result of the collection of experiments offers a possible mechanism for meme creation. An initial event provoking fear is memorized by a group of lateral amygdala, winner neurons possessing high enough levels of CREB and excitability. Once the winners are chosen, the PV interneurons close the gates so losers cannot participate. This restriction lasts for a number of hours such that any future fear-based events (and perhaps other experiences) are co-allocated to the same neurons. But after a day or so, this merging of memories no longer occurs.
The unveiling of this mechanism may help to understand why that flood of memories occurs when recalling historic occasions. But the information also could be used to help develop better memorization techniques in the future. Imagine using a hit song as the basis for course study, or using a striking image or video to open the mind to other useful information. While these may still be theories waiting to be explored, the potential to improved memory is at hand and may one day help you to remember life – not just those associated with tragic events – better.