Forgetting might not be a failure of memory, but rather an adaptive mechanism crucial for learning and decision-making. A team of researchers led by Dr. Tomás Ryan came to this seemingly counterintuitive conclusion in their paper published last August in Cell Reports.1 In their experiments, the researchers found evidence that memories seemingly lost to retroactive interference can be retrieved and updated by environmental cues.
Dropping a memory may represent a form of learning that allows the brain to successfully interact with a changing environment. What’s even more interesting is that hidden memories are not necessarily lost forever; ‘forgetting’ can be reversed. This idea challenges a common perception of forgetfulness as a flaw of memory and opens the door to new avenues of research into memory loss.1,2
Losing the keys, but not the safe
Memories are stored in engrams. These are groups of neurons that store specific memories. The act of ‘remembering’ happens when we reactivate an engram. Forgetting happens when these cell clusters can’t be reactivated, though this doesn’t mean that the memories themselves have been erased. “It’s as if the memories are stored in a safe but you can’t remember the code to unlock it,” Dr. Ryan explains in a press release.2 In practice this means that a memory can’t be retrieved on demand, and maybe a new one has diverted the path of recall, apparently replacing it.
Retroactive interference
One of the most popular theories of how ‘forgetting’ occurs is known as retroactive interference: when two events occur close in time, they overlap in memory, and the newest one “overrides” the old one. Since the rate of forgetting is influenced by environmental conditions, such as smells, sounds, temperature, and even light, researchers have proposed that forgetting acts as a form of learning. They speculate that ‘forgetting’ allows us to change the availability of memory depending on the external environment and how predictable that environment is.1,2
Supplanting a memory
To study the theory of retroactive interference, the researchers gave subjects new information that interfered with their ability to remember previously learned information. Think of it like trying to remember your old phone number after memorizing a new one.
They placed mice in specific environments where they formed associations between certain objects and their surroundings. Later, when presented with both the old, familiar object and a new one, the mice’s behavior served as an indicator of their memory. If they showed equal interest in both objects, it suggested they had forgotten the old one.1
A window in the brain
Meanwhile, they also attached a molecular switch controlled by light to engrams activated during memory formation in each different environment. They could turn the labeled engrams “on” and “off” with a simple manipulation: shining a specific wavelength of light on them.1 When an engram was switched on, it triggered production of a fluorescent protein that allowed the researchers to visualise the activated cells with a microscope and distinguished them from surrounding unactivated engrams.
Unlocking the past
Is it possible to find the lost keys to your mental safe? It turns out…Yes.1
After the memory test, they examined the brains of the mice. Mice without interference showed reactivation of the original engrams, while mice with interference showed activation of engrams formed in the interfering environment. This tells us that interference can create competing memory traces, pushing the original memory aside.
Remarkably the researchers were able to reactivate the lost memories. They did this in two ways, first they put the mouse back into an old situation that the mouse had forgotten. Even a very short re-exposure time (5 minutes) reactivated the engram cells encoding the event at the same level as before forgetting occurred.1 This means the mice were able to access that hidden memory again because the prompts provided by the environment gave them an alternative path to recall the original memory.
Second, they turned on the light. Shining a light on the mouse’s brain activated engram cells that they had given light-activated molecular tags. Shining the light on those cells stimulated the molecular tags, switching the engrams back on. Reactivating those dormant engrams allowed the mice to access their hidden memories and turned on a molecular marker that the researchers could see with a microscope. Moreover, permanently turning off engram cell activation during an interfering situation prevented the mice from forgetting altogether! This fundamental discovery means that new engram activity is required for some types of memory loss.
Shining a light on memory loss
This research offers new insights into memory loss and with that, diseases associated with it. “Instead of the disease causing memory loss because it has somehow degraded the engrams, it may be triggering a very natural process of forgetting but for maladaptive reasons. If so, some of that memory loss may even be reversible because the engrams are intact,” said Dr. Ryan.3
He noted that other studies in rodents with Alzheimer’s disease, age-related and stress-related memory loss showed that stimulating engrams re-expressed memories.3, 4 This is certainly an intriguing possibility.
References
- Autore, L. et al. (2023) ‘Adaptive expression of engrams by retroactive interference’, Cell Reports, 42(8), p. 112999. doi:10.1016/j.celrep.2023.112999.
- Tcddublin (2023) Neuroscientists successfully test theory that forgetting is actually a form of learning, EurekAlert! Available at: https://www.eurekalert.org/news-releases/998879 (Accessed: 27 July 2024).
- Yuhas, D. (2024) Forgotten Memories may remain intact in the brain, Scientific American. Available at: https://www.scientificamerican.com/article/forgotten-memories-may-remain-intact-in-the-brain/ (Accessed: 27 July 2024).
- Ryan, T.J. et al. (2015) ‘Engram cells retain memory under retrograde amnesia’, Science, 348(6238), pp. 1007–1013. doi:10.1126/science.aaa5542.
