Whether we visit a zoo for the first time or learn to ride a bike, we carry memories of our childhood well into adulthood. But what does it explain? as Do these memories last almost a lifetime?
A new study in the journal Scientific advances, conducted by a team of international researchers, has discovered a biological explanation for long-term memory. It focuses on the discovery of the role of a molecule, KIBRA, which serves as “glue” to other molecules, thus solidifying memory formation.
“Previous efforts to understand how molecules store long-term memory focused on the individual actions of individual molecules,” explains André Fenton, a professor of neural sciences at New York University and one of the study’s principal investigators. “Our study shows how they work together to ensure perpetual memory storage.”
“A firmer understanding of how we store our memories will help guide efforts to illuminate and address memory-related conditions in the future,” adds Todd Sacktor, a professor at SUNY Downstate University of Health Sciences and one of the researchers. principals of the study.
It has long been established that neurons store information in memory as a pattern of strong synapses and weak synapses, which determines the connectivity and functioning of neural networks. However, molecules at synapses are unstable, moving continuously in neurons and wearing out and being replaced within hours or days, raising the question: how, then, can memories be stable for years or decades?
In a study with laboratory mice, scientists focused on the role of KIBRA, or kidney and brain-expressed protein, whose human genetic variants are associated with both good and poor memory. They focused on KIBRA’s interactions with other molecules crucial for memory formation, in this case, protein kinase Mzeta (PKMzeta). This enzyme is the most important molecule known to strengthen normal mammalian synapses, but it degrades after a few days.
Their experiments reveal that KIBRA is the “missing link” in long-term memories, acting as a “persistent synaptic tag” or glue that adheres to strong synapses and PKMzeta while avoiding weak synapses.
“During memory formation, synapses involved in the formation are activated, and KIBRA is selectively placed at these synapses,” explains Sacktor, professor of physiology, pharmacology, anesthesiology and neurology at SUNY Downstate. “PKMzeta then attaches to the KIBRA synaptic tag and keeps those synapses strong. This allows the synapses to attach to the newly created KIBRA, attracting more newly created PKMzeta.”
More specifically, his experiments in the Scientific advances paper shows that rip The KIBRA-PKMzeta link erases old memories. Previous work had shown that random increases in PKMzeta in the brain improvement weak or faded memories, which was mysterious because it should have done the opposite by acting on random locations, but the persistent synaptic labeling of KIBRA explains why the additional PKMzeta improved memory, by acting only on KIBRA-labeled sites.
“The persistent synaptic labeling mechanism explains for the first time these results that are clinically relevant to neurological and psychiatric memory disorders,” notes Fenton, who is also on the faculty of the Neuroscience Institute at the University of Langone Medical Center. NY.
The authors of the article point out that the research affirms a concept introduced in 1984 by Francis Crick. Sacktor and Fenton point out that the hypothesis they propose to explain the brain’s role in storing memory despite constant cellular and molecular changes is a Ship of Theseus mechanism, taken from a philosophical argument derived from Greek mythology in which new boards replace the old ones to maintain the Ship of Theseus. during years.
“The persistent synaptic labeling mechanism we found is analogous to how new planks replace old ones to maintain the Ship of Theseus for generations, and allows memories to last for years even when the proteins that maintain the memory are replaced,” says Sacktor . “FrancisCrick intuited this mechanism of the Ship of Theseus, even predicting the role of a protein kinase. But it took 40 years to discover that the components are KIBRA and PKMzeta and to determine the mechanism of their interaction.”
The study also included researchers from Canada’s McGill University, Germany’s Münster University Hospital and the University of Texas Medical School in Houston.
This work was supported by grants from the National Institutes of Health (R37 MH057068, R01 MH115304, R01 NS105472, R01 MH132204, R01 NS108190), the Natural Sciences and Engineering Research Council of Canada Discovery (203523), and the Garry and Sarah S .Sklar Fund.