Summary: A new study reveals the role of the molecule KIBRA in the formation of long-term memories. The researchers discovered that KIBRA acts as a “glue” and binds to the PKMzeta enzyme to strengthen and stabilize synapses, which are key to memory retention.
The discovery could lead to new treatments for memory-related conditions. The findings confirm a long-standing hypothesis about memory storage mechanisms.
Key facts:
- The role of KIBRA: Acts as a molecular “glue” for the formation of long-term memory.
- Memory stabilization: KIBRA binds with PKMzeta to strengthen synapses.
- Clinical potential: May inform treatment of memory-related disorders.
Source: NYU
Whether it was the first time we visited the zoo or when we learned to ride a bike, we carry our childhood memories well into adulthood. But what does it explain how these memories last almost a lifetime?
New study in journal Scientific advances, led by a team of international researchers, revealed a biological explanation for long-term memories. It focuses on the discovery of the role of a molecule, KIBRA, that serves as a “glue” to other molecules, thereby cementing memory formation.
“Previous efforts to understand how molecules store long-term memory have focused on the individual actions of individual molecules,” explains André Fenton, professor of neural science at New York University and one of the principal investigators of the study.
“Our study shows how they work together to ensure eternal memory storage.”
“A better understanding of how we store our memories will help guide future efforts to illuminate and solve memory-related problems,” adds Todd Sacktor, a professor at SUNY Downstate Health Sciences University and one of the study’s principal investigators.
Neurons have long been known to store information in memory as a pattern of strong and weak synapses, which determines the connectivity and function of neuronal networks.
But molecules in synapses are unstable, constantly moving around neurons and wearing out and being replaced within hours to days, raising the question: So how can memories be stable for years to decades?
In a study in laboratory mice, the researchers focused on the role of KIBRA, a protein expressed by the kidney and brain, whose human genetic variants are associated with both good and bad memory.
They focused on the interactions of KIBRA 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, serving as a “permanent synaptic marker” or glue that sticks to strong synapses and PKMzeta while avoiding weak synapses.
“During memory formation, the synapses involved in the formation are activated – and KIBRA is selectively located at these synapses,” explains Sacktor, professor of physiology, pharmacology, anesthesiology and neurology at SUNY Downstate.
“PKMzeta then binds to the synaptic marker KIBRA and keeps those synapses strong. This allows the synapses to hold on to the newly produced KIBRA and attract more newly produced PKMzeta.”
More specifically, their experiments in Scientific advances the paper shows it breaking the KIBRA-PKMzet bond erases the old memory. Previous work has shown that PKMzeta increases randomly in the brain improves weak or faded memories, which was puzzling because it was supposed to do the opposite by acting on random sites, but the persistent synaptic tagging from KIBRA explains why another PKMzeta improves memory by only acting on KIBRA-marked sites.
“The mechanism of persistent synaptic tagging explains for the first time these results, which are clinically relevant to neurological and psychiatric memory disorders,” notes Fenton, who is also on the faculty at NYU Langone Medical Center’s Neuroscience Institute.
The authors of the paper note that the research confirms a concept introduced in 1984 by Francis Crick. Sacktor and Fenton point out that his proposed hypothesis, which explains the brain’s role in memory storage despite constant cellular and molecular changes, is the Ship of Theseus mechanism—borrowed from a philosophical argument derived from Greek mythology in which new planks replace old planks to keep Ship of Theseus. flight.
“The persistent synaptic tagging mechanism we found is analogous to how new planks replace old planks to sustain the Ship of Theseus over generations, allowing memories to persist for years even as they are replaced by memory-maintaining proteins,” says Sacktor.
“Francis Crick guessed this ship of Theseus mechanism, even predicting the role of protein kinase. But it took 40 years to figure out that the components are KIBRA and PKMzeta and figure out a mechanism for their interaction.”
The study also included researchers from Canada’s McGill University, Germany’s University Hospital Münster and the University of Texas Medical School in Houston.
Funding: This work was supported by grants from the National Institutes of Health (R37 MH057068, R01 MH115304, R01 NS105472, R01 MH132204, R01 NS108190), Natural Sciences and Engineering Research Council of Canada Discovery (203523), and Sára. The Glass Fund.
About this news from the field of genetics and memory research
Author: James Devitt
Source: NYU
Contact: James Devitt – NYU
Picture: Image is credited to Neuroscience News
Original Research: Open access.
“KIBRA Anchoring PKMζ Action Maintains Memory Persistence” by André Fenton et al. Scientific advances
Abstract
KIBRA anchoring the action of PKMζ maintains memory persistence
How can short-lived molecules selectively maintain potentiation of activated synapses to maintain long-term memory?
Here we find adapter protein expressed by kidney and brain (KIBRA), a postsynaptic scaffolding protein genetically linked to human memory performance, complexes with protein kinase Mzeta (PKMζ), anchoring the potentiating effect of the kinase to maintain long-term late-phase potentiation (late-LTP) at activated synapses.
Two structurally distinct antagonists of KIBRA-PKMζ dimerization disrupt established late-LTP and long-term spatial memory, but neither measurably affects basal synaptic transmission.
Neither antagonist affects PKMζ-independent LTP or memory, which are maintained by PKC compensation in ζ-knockout mice; both substances therefore require PKMζ for their effect. KIBRA-PKMζ complexes retain 1-month-old memory despite PKMζ turnover.
Thus, it is not PKMζ alone or KIBRA alone, but the constant interaction between the two that maintains late LTP and long-term memory.