The Mystery of Memory
By Evan Lin
While we have thoroughly traversed much of the knowledge existing in anatomy and physiology, one essential, even lifesaving ability of the animal body remains as mysterious as it is remarkable: memory.
After all, knowing your left from right or recognizing songs you’ve heard in the past doesn’t just magically happen. Memories are physically stored in cells and are unique from each other. We call these physical traces of memories “engrams”, and for decades, scientists have attempted to discover the nature of these imprints.
Neurons
Let’s begin with the center of animal nervous systems: the brain. The brain is a mosaic of different cell types, each with their own unique properties. The most common brain cells are neurons and non-neuronal cells called glia. The average adult human brain contains approximately 100 billion neurons, and just as many, if not more, glia.
Neurons are the cells in the brain that send and receive electrical and chemical signals, transmitting information to other neurons and cells throughout the body. A neuron is made up of three basic parts: the cell body, branching dendrites that receive signals from other neurons, and the axon, a long fiber that carries signals away from the cell body.
When a neuron receives a signal, it generates an electric impulse called an action potential that travels through the axon and triggers the release of neurotransmitters, small chemical molecules, at the axon terminals. These neurotransmitters leave the terminals, cross a small gap called the synapse, and spread to the dendrites of a neighboring neuron, passing the signal on to that neuron.
In terms of memory, the neurons that are observed sending signals during a learning or remembering experience are dubbed engram cells. The term “experience” highlights the difficulty in classifying memory and learning; it’s anything that can be “remembered” by our brain, such as being recalled or re-experienced. Engram cells undergo long-term physical or chemical changes and can be selectively reactivated to produce the retrieval of that experience. However, knowing that certain neurons get activated during memory building and retrieval is not enough. Scientists want to find out how this happens, down to the molecular scale. This brings us to one of the oldest theories regarding the basis of memory: long-term potentiation.
LTP Theory
In the 1970s, it was found that as an animal learned something, synapses bulked up. Specifically, bulges, called synaptic boutons, grew at axon terminals, while hairlike protrusions, called spines, grew at dendrites, often in response to high-frequency electrical stimulation of a neuron. This would lead to an increase in the number of contact points between the axon terminal of one neuron and the dendrites of the next, strengthening the long-term connection between two given neurons.
This process was known as long-term potentiation (LTP), and for decades, scientists accepted it as the physical basis of memory storage and strengthening; however, research from David Glanzman, a neuroscientist at UCLA, and Susumu Tonegawa, a Nobel-Prize winning neuroscientist at MIT, may overturn the LTP theory.
Scientists often consider learning and remembering as similar actions in terms of triggering neuronal activity, because the two are so hard to distinguish. Glanzman studied the sea slug Aplysia, which protectively withdraw their siphon and gill when shocked in the tail as a memory mechanism. When they were shocked repeatedly by Glanzman’s team, they withdrew faster, indicating a stronger memory of the shock. Glanzman and his researchers observed more message-sending bumps in synapses between neurons that were responsible for sensing the shock and neurons that were responsible for commanding the siphon and gill to move, which corresponded with LTP theory. Then, the team introduced a drug into the slugs which prevented protein production, resulting in some of the bumps being lost. The slugs displayed weaker memories of the shock after this, once again supporting the theory that LTP was the difference between a strong memory and a weaker one.
However, the next question Glanzman asked turned out to be a curveball. If LTP was the main player in memory fortification, then the new contact points formed when a memory is made or strengthened should be the same ones that disappear when that memory is lost. Using the same sea snails, he found that in sea snails which forgot about the shock and withdrawal process, the contact points (bumps) that disappeared were far from being exclusively the ones that had formed during the repeated shocks from earlier in the experiment. Rather, the disappearance of contact points was completely random across even neurons not involved in this particular pathway. These findings challenged LTP theory of memory storage and recall.
Perhaps more glaring are the findings from Tonegawa’s lab. Tonegawa’s team conditioned mice to fear a particular cage and genetically marked the cells that somehow store that particular fear memory, likely by using fluorescent lights to determine which neurons fired action potentials in moments of “fear.” Like Glanzman’s team, they observed that these neurons developed more dendritic spines when the mice formed the memory, evidence of LTP theory. However, when they used a drug to cause amnesia and wipe away all the dendritic spines, the memory of the cage wasn’t lost. With optogenetics, the researchers could activate those neurons and the memory they still somehow held.
The findings of these two researchers resulted in the questioning of LTP, or synaptic strength, as the true physical form of memory. While it was clear it played a part in the strengthening of long-term memory as a result of remembering or learning, it’s now evident that the cellular mechanisms for calling up memories are not necessarily the same ones that store them. Many scientists believe that synaptic strength is only responsible for the recall of memories.
Conclusion
To this day we don’t know the physical basis of memory. We know that engram cells exist; that is, specific neurons are responsible for the retaining and retrieval of certain memories, and we know that these engram cells demonstrate strong evidence of LTP, indicating memory “strength” depends on synaptic plasticity, but we still don’t know the actual way a memory is stored within a neuron. Even theories that are widely accepted are often revised due to different findings and suggestions. For example, some scientists, such as Glanzman, suggest that memories are stored RNA and nucleic acids. Yet other scientists raise the possibility of epigenetic regulation of memory, which could lead to a completely new way of examining learning and remembering.
Regardless of what form of memory storage is the true one, the job of finding out the biochemical encoding of the myriad memories humans experience seems even more impossible. How are pitches in a song memorized? Location and relative location? Or where you last left your car keys? How is our ability to recognize millions upon millions of objects and specific information about them stored within neurons? And what makes all these chemical traces, in whatever shape they may take–RNA, DNA, epigenetics, neurons themselves–unique and distinguishable from one another? Once we accept that the engram exists–that there is a physical, molecular basis to all of these complexities–memory only becomes more complex than ever.
But hey, we have a good starting place. At least we know where these secrets likely lie. Who knows? It could be you, future scientist, who uncovers them and resolves the mystery of memory.
Works Cited
“Cells of the Brain.” Dana Foundation, https://dana.org/article/cells-of-the-brain/. Accessed 1 Jan. 2023.
Somewhere in the Brain Is a Storage Device for Memories. 24 Jan. 2018, https://www.sciencenews.org/article/memory-brain-engram-neuroscience.
“The Memory-Transfer Episode.” Https://Www.Apa.Org, https://www.apa.org/monitor/2010/06/memory-transfer. Accessed 1 Jan. 2023.
Tonegawa, Susumu, et al. “The Role of Engram Cells in the Systems Consolidation of Memory.” Nature Reviews Neuroscience, vol. 19, no. 8, Aug. 2018, pp. 485–98. www.nature.com, https://doi.org/10.1038/s41583-018-0031-2.
