Resume: A new study reveals the role of the molecule KIBRA in forming long-term memories. Researchers found that KIBRA acts as a ‘glue’ that binds with the enzyme PKMzeta to strengthen and stabilize synapses, crucial for memory retention.
This discovery could lead to new treatments for memory-related disorders. The findings confirm a long-standing hypothesis about memory storage mechanisms.
Key Facts:
- KIBRA’s role: Acts as a molecular “glue” for the formation of long-term memory.
- Memory stabilization: KIBRA binds with PKMzeta to strengthen synapses.
- Clinical potential: May provide information about treatments for memory-related disorders.
Source: N.Y.U
Whether it’s our first visit to the zoo or learning to ride a bike, we have memories from our childhood that last well into adulthood. But what explains How These memories last almost a lifetime?
A new study in the journal Scientific progress, conducted by a team of international researchers, has uncovered a biological explanation for long-term memories. It revolves around the discovery of the role of a molecule, KIBRA, that serves as a ‘glue’ for other molecules, thereby strengthening memory formation.
“Previous attempts to understand how molecules store long-term memory have focused on the individual actions of single molecules,” explains André Fenton, professor of neural sciences at New York University and one of the study’s lead investigators.
“Our research shows how they work together to ensure persistent memory storage.”
“A better understanding of how we retain our memories will help efforts to illuminate and address memory-related disorders in the future,” said Todd Sacktor, a professor at SUNY Downstate Health Sciences University and one of the study’s principal investigators.
It has long been known that neurons store information in memory as the pattern of strong synapses and weak synapses, which determines the connectivity and function of neural networks.
However, the molecules in synapses are unstable and constantly move through the neurons. They become worn out and replaced within hours or days. That raises the question: how can memories remain stable for years or decades?
In a study using laboratory mice, scientists focused on the role of KIBRA, or kidney-brain expressed protein, whose human genetic variants are associated with both good and bad 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 crucial molecule for strengthening normal mammalian synapses as known, but it is broken down after a few days.
Their experiments show that KIBRA is the ‘missing link’ in long-term memories, serving as a ‘persistent synaptic label’ or glue, sticking to strong synapses and to PKMzeta while avoiding weak synapses.
“During memory formation, the synapses involved in the formation are activated – and KIBRA is selectively positioned in 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 stick to newly made KIBRA, attracting more newly made PKMzeta.”
More specifically, their experiments in the Scientific progress paper shows that break the KIBRA-PKMzeta band erases old memories. Previous work had shown that PKMzeta increases randomly in the brain improves weak or faded memories, which was mysterious because it should have done the opposite by acting on random sites, but the persistent synaptic tagging by KIBRA explains why the extra PKMzeta improved memory, by only acting on the sites tagged by KIBRA.
“The persistent synaptic tagging 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 NYU Langone Medical Center.
The paper’s authors note that the research confirms a concept introduced by Francis Crick in 1984. Sacktor and Fenton point out that his proposed hypothesis to explain the brain’s role in memory storage, despite ongoing cellular and molecular changes, is a ship of Theseus mechanism — borrowed from a philosophical argument stemming from Greek mythology, in which new planks replace old ones to keep the ship of Theseus afloat for long years.
“The persistent synaptic tagging mechanism we found is analogous to the way new planks replace old planks to maintain Theseus’ ship for generations, and ensures that memories last for years even as the proteins that maintain memory are replaced ,” says Sacktor.
“Francis Crick sensed this Theseus ship mechanism and even predicted the role of a protein kinase. But it took forty years to discover that the components are KIBRA and PKMzeta and to work out 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.
Financing: 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.
About this genetics and memory research news
Author: James Devitt
Source: N.Y.U
Contact: James Devitt-NYU
Image: The image is credited to Neuroscience News
Original research: Open access.
“KIBRA anchoring the action of PKMζ maintains memory persistence” by André Fenton et al. Scientific progress
Abstract
KIBRA anchoring the action of PKMζ maintains memory persistence
How can short-lived molecules selectively maintain the strengthening of activated synapses to preserve long-term memory?
Here we find kidney and brain expressed adapter protein (KIBRA), a postsynaptic support protein genetically linked to human memory performance, complexes with protein kinase Mzeta (PKMζ), which anchors the kinase’s potentiating action to prevent late -phase potentiation in the long term (late phase). -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 maintained by compensating PKCs in ζ-knockout mice; both drugs therefore require PKMζ for their effect. KIBRA-PKMζ complexes retain 1-month-old memory despite PKMζ turnover.
Therefore, it is not PKMζ alone, nor KIBRA alone, but the ongoing interaction between the two that maintains late-LTP and long-term memory.