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Whether it’s the thrill of a first visit to the zoo or the triumphant moment of learning to ride a bicycle, childhood memories often stay with us throughout our lives. But what enables these memories to endure for decades? A groundbreaking study published in the journal Science Advances has unveiled a biological explanation for the longevity of long-term memories, shedding light on the intricate molecular mechanisms that preserve our past.
The study, conducted by an international team of researchers, reveals the pivotal role of a molecule called KIBRA, which acts as a “glue” to secure memory formation. “Previous efforts to understand how molecules store long-term memory focused on the individual actions of single molecules,” explains André Fenton, a professor of neural science at New York University and one of the study’s principal investigators. “Our study shows how they work together to ensure perpetual memory storage.”
Todd Sacktor, a professor at SUNY Downstate Health Sciences University and another principal investigator, emphasizes the significance of this discovery. “A firmer understanding of how we keep our memories will help guide efforts to illuminate and address memory-related afflictions in the future,” he says.
The Puzzle of Persistent Memories
Neurons store information in memory through patterns of strong and weak synapses, which define the connectivity and function of neural networks. However, the molecules within synapses are not permanent; they move around, degrade, and are replaced within hours to days. This constant molecular turnover raises the question: How can memories remain stable for years or even decades?
KIBRA: The Memory Molecule
The researchers used laboratory mice to investigate the role of KIBRA, or kidney and brain expressed protein, which has genetic variants linked to both good and poor memory in humans. They discovered that KIBRA interacts with another crucial molecule, protein kinase Mzeta (PKMzeta), known for its role in strengthening synapses. While PKMzeta degrades after a few days, KIBRA serves as a “persistent synaptic tag” that retains PKMzeta at specific synapses, solidifying memory formation.
“During memory formation, the synapses involved are activated, and KIBRA is selectively positioned in these synapses,” explains Sacktor. “PKMzeta then attaches to the KIBRA-synaptic tag and keeps those synapses strong, attracting more newly made PKMzeta.” This process ensures that the synapses remain robust, preserving the memory.
Breaking the Bond, Erasing the Memory
The experiments detailed in the Science Advances paper demonstrate that disrupting the bond between KIBRA and PKMzeta can erase old memories. Previous research had shown that increasing PKMzeta levels in the brain could enhance weak or faded memories, which was puzzling because it should have affected random synapses. The discovery of KIBRA’s role clarifies this mystery, revealing that PKMzeta enhances memory by acting only at KIBRA-tagged sites.
A Concept from Greek Mythology
The study’s findings also support a concept proposed by Francis Crick in 1984, known as the Theseus’s Ship mechanism. This philosophical argument from Greek mythology suggests that as new planks replace old ones, Theseus’s Ship remains the same. Similarly, the persistent synaptic tagging mechanism allows memories to last for years even as the proteins maintaining them are replaced.
“The persistent synaptic tagging mechanism we found is analogous to how new planks replace old planks to maintain Theseus’s Ship for generations, allowing memories to last for years,” says Sacktor. “Francis Crick intuited this mechanism, predicting the role for a protein kinase. It took 40 years to discover that the components are KIBRA and PKMzeta and to work out their interaction.”
Future Implications
This discovery, involving researchers from McGill University in Canada, the University Hospital of Münster in Germany, and the University of Texas Medical School at Houston, has significant implications. By enhancing our understanding of memory storage mechanisms, it opens new avenues for addressing memory-related neurological and psychiatric disorders.
The study was supported by grants from the National Institutes of Health, the Natural Sciences and Engineering Research Council of Canada, and the Garry and Sarah S. Sklar Fund, highlighting the collaborative effort to unravel the mysteries of memory.
Conclusion
The discovery of KIBRA’s role in memory formation marks a significant milestone in neuroscience. By elucidating how memories can last a lifetime despite the continuous molecular changes in our brains, this research paves the way for new strategies to combat memory-related diseases and enhance our understanding of the human mind.
