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Environmental feedback, engrams, and functional features of the brain: Memories are made of this?

By Dr Doug Witherspoon - 10th Sep 2023


As flawed creatures clinging to this spinning blue marble, we all forget things from time to time. This of course can be a cause of anxiety, especially in older years, and may raise fears that forgetfulness may be a portent of some life-changing neurological disorder.

Last month, however, the first results from some experimental tests were released that were designed to look at whether ‘forgetting things’ may represent a type of learning and may not be all negative. The core aim of the work by researchers at the Trinity Biomedical Sciences Institute is to advance our understanding of diseases such as Alzheimer’s.

In 2022, work by the same group suggested that rather than being a flaw or a ‘problem’, forgetting certain things may in fact represent a form of learning and an inherently functional feature of the brain. In other words, forgetting things may be all ‘part of the plan’ for our brains and could be based on predictability and environmental feedback.

In the dynamic, changing environment in which we all live, the authors postulate that forgetting some memories may actually benefit us and help foster improved decision-making, as well as flexibility and adaptability. This particularly applies if the memories were gained in circumstances that the brain does not consider ‘important’ to our current environment. Losing these memories, they suggest, may benefit us as a whole.

The team focused on different types of ‘forgetting’, including everyday forgetfulness, and how they affect particular aspects of the brain’s memory functions. Another type of forgetfulness they studied was termed ‘retroactive interference’, whereby things that occur closely in time can result in forgetting recently formed memories.

For example, mice were prompted to associate an object with a room or a certain context, and were then required to recognise that object when it was out of context or in a different location. They found that the mice forget these memory associations when different experiences impinge on that initial memory.

This led them to genetically label a contextual engram in the brains of the mice, which allowed them to track the functioning and activation of this group of brain cells after forgetfulness had taken place. They also employed optogenetics, an experimental technique in biological research that combines optics and genetics in technologies that can control well-defined events in the cells of living animal tissue.

With this technique, they discovered that stimulating these engram cells with light resulted in the retrieval of apparently ‘lost’ memories in different behavioural situations. In addition, when the mice were ‘fed’ with different new experiences that had some connection with lost memories, the forgotten engrams could in fact be rejuvenated.

The research shows that, potentially, ‘natural’ forgetfulness is reversible in certain circumstances. It doesn’t take much imagination to think of the possible implications for certain diseases, such as Alzheimer’s, where ‘everyday’ forgetfulness may be mistakenly activated by brain disease.

Irish Research Council Postgraduate Scholar Dr Livia Autore, who spearheaded the work, commented: “Our findings here support the idea that competition between engrams affects recall and that the forgotten memory trace can be reactivated by both natural and artificial cues, as well as updated with new information. The continuous flow of environmental changes leads to the encoding of multiple engrams that compete for their consolidation and expression.”

“So while some may persist undisturbed, some will be subjected to interference by new incoming and prevailing information. However, the interfered memories can still be reactivated by surrounding cues leading to memory expression or by misleading or novel experiences ending up in an updated behavioural outcome.”

Dr Tomás Ryan, Associate Professor in the School of Biochemistry and Immunology and the Trinity College Institute of Neuroscience at Trinity College Dublin, and lead author, added: “Memories are stored in ensembles of neurons called engram cells and successful recall of these memories involves the reactivation of these ensembles. By logical extension, forgetting occurs when engram cells cannot be reactivated.”

“However, it is increasingly becoming clear that the memories themselves are still there, but the specific ensembles are not activated and so the memory is not recalled. It’s as if the memories are stored in a safe, but you can’t remember the code to unlock it.”

If the researchers could come up with a way to help forget only the memories that embarrass us or make us uncomfortable in some way, there may be a few takers for that kind of research.

If you want to check out the study in more detail, it was published recently in Cell Reports.

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