What does a memory look like?

Think of your favorite memory. You can probably visualize the setting, feel the emotions you experienced, and recreate the smells, tastes, or sounds of the memory in your mind. You know what recalling a specific memory feels like, but what does that memory look like in your brain? Could you point to that memory in physical space? Learning and memory researchers call the physical representation of a memory its engram. 

Combinations of active neurons (filled circles) in the brain are relevant to different memory engrams. There can be some overlap between different engrams and the neurons that participate in an engram can shift over time.

The engram was first described in 1921 as the lasting physical change produced by a stimulus [1]. An engram-producing stimulus could be as simple as a loud noise or electric shock and evidence of that stimulus lasts in the brain for an extended period. Engrams are believed to be made up of neurons active at the time of the event, which form strengthened connections with one another [2]. Different combinations of neurons make up engrams for different memories. When the memory is recalled later, the relevant engram population becomes active again. Scientists can use these engram properties to manipulate memories and their associated behaviors in the laboratory.

Using modern neuroscience techniques, researchers made mice falsely recall fearful memories. By stimulating the fear engram cells from a previous fearful experience, mice froze with fear even when no threat was present [3]. Neuroscientists have even been able to create false memories in mice by reactivating existing engrams in new settings. When researchers activated engram cells for a neutral setting during a fear-inducing experience in a different location, they made mice fear the neutral setting that never contained aversive events [4]. 

Despite our ability to manipulate engrams in the lab, there are many open questions left to answer. For example, where do engrams reside in the brain? Some engrams are first formed in the hippocampus before migrating to the cortex, the outermost layers of the brain. Yet many studies demonstrate evidence of cortical engrams right away [5]. Furthermore, engram populations appear in structures all over the brain, not just in the hippocampus or cortex, so the exact location of a single memory may be distributed across many brain structures [6,7]. The content of a memory may influence which brain areas house its engram. 

This spatial distribution of memories leads to another open question. Why do engram populations appear to change over time? In other words, why do some cells enter and others leave an engram? This shifting of engram populations is known as representational drift [8,9]. These gradual adjustments in the cell population that makes up an engram may help to keep it separate from newly formed engrams [8]. However, more research on representational drift is required to understand the purpose of this process. 

Answering these questions about the nature of engrams is more relevant than ever as dementia and Alzheimer disease rates rise [10]. If we can understand the full picture of engram formation and maintenance, we will move closer to identifying and treating the causes of dementia, Alzheimer’s disease, and other forms of memory loss.

Cited Works 

[1] Semon, R.W. and Simon, L. (1921) The Mneme. London, New York: G. Allen & Unwin Ltd., The Macmillan Company.

[2] Josselyn, S. A. et al. (2015). Finding the engram. Nature Reviews Neuroscience, 16(9), 521-534.

[3] Liu, X. et al. (2012). Optogenetic stimulation of a hippocampal engram activates fear memory recall. Nature, 484(7394), 381-385.

[4] Ramirez, S. et al. (2013). Creating a false memory in the hippocampus. Science, 341(6144), 387-391.

[5] Kitamura, T. et al. (2017). Engrams and circuits crucial for systems consolidation of a memory. Science, 356(6333), 73-78.

[6] Eichenbaum, H. (2016). Still searching for the engram. Learning & behavior, 44, 209-222.

[7] Lashley, K. S. (1950). In search of the engram. Symposiums of the Society of Experimental Biology, 4, 454–482.

[8] Driscoll, L. N. et al. (2022). Representational drift: Emerging theories for continual learning and experimental future directions. Current Opinion in Neurobiology, 76, 102609.

[9] Rule, M. E. et al. (2019). Causes and consequences of representational drift. Current opinion in neurobiology, 58, 141-147.

[10] Rizzi, L. et al. (2014). Global epidemiology of dementia: Alzheimer’s and vascular types. BioMed research international, 2014.

Edited by Alexandra Fink