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A new study published in Science Advances has uncovered a biological explanation for the longevity of long-term memories. The research, conducted by a team of international scientists, focuses on the role of a molecule called KIBRA in memory formation. Previous research had investigated how individual molecules contribute to memory storage, but this study shows how molecules work together to solidify memories. Understanding the mechanisms behind memory formation could lead to advancements in treating memory-related disorders in the future.

Neurons store information through patterns of synapses, both strong and weak, which determine the connectivity and function of neural networks. However, the molecules in synapses are constantly changing, raising the question of how memories can remain stable for years to decades. The researchers focused on the role of KIBRA, which interacts with protein kinase Mzeta (PKMzeta) to form a “persistent synaptic tag” that sticks to strong synapses and helps maintain memories over time. This mechanism sheds light on how memories can endure despite molecular turnover in the brain.

Their experiments with laboratory mice revealed that breaking the KIBRA-PKMzeta bond could erase old memories. Previous studies had shown that increasing PKMzeta in the brain could enhance weak or fading memories, but the mechanism behind this enhancement was unclear. The discovery of the persistent synaptic tagging by KIBRA explains how additional PKMzeta can improve memory retention by targeting specific sites in the brain. This mechanism has implications for understanding neurological and psychiatric disorders related to memory.

The study’s findings also support a hypothesis proposed by Francis Crick in 1984, which suggests that the brain’s ability to store memories despite cellular and molecular changes is akin to Theseus’s Ship, a philosophical argument from Greek mythology. The researchers note that the persistent synaptic tagging mechanism they discovered mirrors how new planks replace old planks to maintain Theseus’s Ship over time. This insight into memory formation provides a deeper understanding of how memories are stored and maintained in the brain.

The collaborative research involved scientists from various institutions, including McGill University in Canada, University Hospital of Münster in Germany, and the University of Texas Medical School at Houston. The study was supported by grants from the National Institutes of Health and the Natural Sciences and Engineering Research Council of Canada. By uncovering the molecular mechanisms behind memory formation, this research opens up new possibilities for developing interventions for memory-related disorders and enhancing our understanding of how memories persist throughout a lifetime.

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