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Could Forgetting Be an Essential Brain Function?

Does “forgetting” serve as a functional aspect of the brain? Neuroscientists’ experiments point to learning.

Initial findings from neuroscientists’ experiments suggest that the concept of “forgetting” may not necessarily be negative. It’s being viewed as a form of learning, and these findings support this notion.

The scientists had previously suggested that alterations in our memory retrieval might result from environmental cues and predictability. They argued that rather than being a flaw, forgetting could be a deliberate feature of the brain.

This feature allows the brain to effectively adapt to constantly changing surroundings.

Living in a dynamic world, like ours and that of various other organisms, could benefit from forgetting certain memories. This process may contribute to more adaptable behavior and improved decision-making. When memories aren’t entirely relevant to our present environment, the act of forgetting could potentially lead to positive changes and enhance our overall well-being.

In a recent publication in the esteemed international journal Cell Reports, a series of groundbreaking experimental studies has been introduced. These studies delve into the impact of natural, everyday forgetting on specific memories within the brain’s processes.

The research team focused on exploring a type of forgetting termed retroactive interference, which occurs when closely timed experiences lead to the loss of recently formed memories. Their study involved observing mice tasked with linking a specific object to a particular setting or room, and subsequently identifying that same object when placed in a different context. However, the mice tended to forget these connections when competing experiences were introduced, causing interference with the initial memory.

In investigating the impact of forgetting on memory, a team of neuroscientists employed genetic labeling to mark contextual “engrams” (clusters of brain cells housing specific memories) within the mice’s brains. They then tracked these cells’ activity and function after the forgetting process occurred. Through optogenetics, they discovered that stimulating these engram cells with light effectively retrieved seemingly lost memories across various behavioral situations. Additionally, exposing the mice to new experiences related to the forgotten memories naturally rejuvenated these ‘lost’ engrams.

Dr. Tomás Ryan, the lead author of the recently published journal article, serves as an Associate Professor in the School of Biochemistry and Immunology and the Trinity College Institute of Neuroscience at Trinity College Dublin.

“Memories reside within groups of neurons referred to as ‘engram cells,’ and successful memory recall involves reactivating these cell clusters. Consequently, forgetting happens when these engram cells cannot be reactivated. However, it’s increasingly evident that while the memories persist, the specific ensembles remain inactive, leading to the inability to recall. It’s akin to having memories stored in a secure place, but the code to access them is forgotten.”

Dr. Ryan, whose research team operates from the Trinity Biomedical Sciences Institute (TBSI)

“Our discoveries bolster the concept that competition among engrams impacts recall, and that forgotten memory traces can be reactivated by both natural and artificial cues, while also being updated with new information. The continual flux of environmental changes prompts the encoding of numerous engrams that vie for consolidation and expression.”

Dr. Livia Autore, an Irish Research Council (IRC) Postgraduate Scholar who led this research in the Ryan Lab at Trinity,

As various memories persist undisturbed, others may encounter interference due to the arrival of new and prevailing information. Despite this interference, these affected memories can still be reactivated through cues from the surroundings, thus influencing memory recall, or by encountering misleading or new experiences that result in an altered behavioral response.

Understanding that “natural forgetting” can be reversed under specific conditions carries substantial importance, especially concerning disease conditions. For instance, in individuals living with Alzheimer’s disease, these routine forgetting processes might erroneously activate due to brain disease. This finding holds significant implications for understanding and potentially addressing memory-related conditions like Alzheimer’s.

Summary

Long-term memories are stored as configurations of neuronal ensembles, termed engrams. Although investigation of engram cell properties and functionality in memory recall has been extensive, less is known about how engram cells are affected by forgetting. We describe a form of interference-based forgetting using an object memory behavioral paradigm. By using activity-dependent cell labeling, we show that although retroactive interference results in decreased engram cell reactivation during recall trials, optogenetic stimulation of the labeled engram cells is sufficient to induce memory retrieval. Forgotten engrams may be reinstated via the presentation of similar or related environmental information. Furthermore, we demonstrate that engram activity is necessary for interference to occur. Taken together, these findings indicate that retroactive interference modules engram expression in a manner that is both reversible and updatable. Inference may constitute a form of adaptive forgetting where, in everyday life, new perceptual and environmental inputs modulate the natural forgetting process.

https://www.sciencedirect.com/science/article/pii/S2211124723010100

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