Summary: A new study reveals the role of the molecule KIBRA in the formation of long-term memories. The researchers found that KIBRA acts as a “glue,” binding to the enzyme PKMzeta to strengthen and stabilize synapses, which are essential for memory retention.
This discovery could lead to new treatments for memory-related conditions. The results confirm a long-standing hypothesis about memory storage mechanisms.
Highlights:
- The role of KIBRA: Acts as a molecular “glue” for the formation of long-term memory.
- Memory stabilization: KIBRA binds to PKMzeta to strengthen synapses.
- Clinical potential: Could shed light on treatments for memory-related disorders.
Source: New York University
Whether it’s a first visit to a zoo or learning to ride a bike, we carry memories from our childhood into adulthood. But what explains how These memories last almost a lifetime?
A new study in the journal Scientists progress, led by a team of international researchers, has discovered a biological explanation for long-term memories. It revolves around the discovery of the role of a molecule, KIBRA, which serves as “glue” for other molecules, thus solidifying the formation of memory.
“Previous efforts to understand how molecules store long-term memory have focused on the individual actions of single molecules,” says André Fenton, professor of neural sciences at New York University and one of the principal investigators of the study.
“Our study shows how they work together to ensure perpetual memory storage.”
“A better understanding of how we retain our memories will help guide efforts to illuminate and treat memory-related afflictions in the future,” adds Todd Sacktor, a professor at SUNY Downstate Health Sciences University and the one of the principal investigators of the study.
It has long been established that neurons store information in memory in the form of strong synapses and weak synapses, which determine the connectivity and function of neural networks.
However, molecules at synapses are unstable, continually moving within neurons, wearing out and being replaced within hours or even days, which raises the question: how, then, can memories be stable for years, or even decades?
In a study using laboratory mice, scientists focused on the role of KIBRA, or protein expressed by the kidneys and brain, human genetic variants of which are associated with good and poor memory.
They focused on KIBRA’s interactions with other molecules essential for memory formation, in this case, Mzeta protein kinase (PKMzeta). This enzyme is the most crucial molecule known to strengthen normal synapses in mammals, but it degrades after a few days.
Their experiments reveal that KIBRA is the “missing link” in long-term memory, serving as a “persistent synaptic beacon,” 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 positioned in these synapses,” says Sacktor, professor of physiology, pharmacology, anesthesiology and neurology at SUNY Downstate.
“PKMzeta then attaches to the synaptic tag KIBRA and keeps these synapses strong. This allows the synapses to stick to the new KIBRA, thereby attracting more newly formed PKMzeta. »
More specifically, their experiences in the Scientists progress paper shows that breakup the KIBRA-PKMzeta connection erases the old memory. Previous work showed that random increases in PKMzeta in the brain improved weak or faded memories, which was mysterious because it should have done the opposite by acting at random locations, but the persistent synaptic marking by KIBRA explains why the additional PKMzeta improved memory, acting only at the sites marked by KIBRA.
“The mechanism of persistent synaptic marking explains for the first time these findings that are clinically relevant to neurological and psychiatric memory disorders,” observes Fenton, who is also on the faculty of the Neuroscience Institute at NYU Langone Medical Center .
The authors of the study point out that this research confirms a concept introduced in 1984 by Francis Crick. Sacktor and Fenton point out that his hypothesis for explaining the brain’s role in storing memory despite constant cellular and molecular changes is a “Ship of Theseus” mechanism, borrowed from a philosophical argument from Greek mythology in which new planks replace the old ones to hold Theseus’ ship together for years.
“The persistent synaptic marking mechanism we discovered is analogous to how new boards replace old boards to maintain Theseus’s ship for generations, and allows memories to last for years even if the proteins that maintain memory are replaced,” says Sacktor.
“Francis Crick 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 understand the mechanism of their interaction.
The study also included researchers from McGill University in Canada, University Hospital Münster in Germany 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), the Natural Sciences and Engineering Research Council of Canada Discovery (203523), and the Garry and Sarah S. Sklar Fund.
About this research news in genetics and memory
Author: James Devitt
Source: NYU
Contact: James Devitt – NYU
Picture: Image credited to Neuroscience News
Original research: Free access.
“KIBRA anchoring the action of PKMζ maintains memory persistence” by André Fenton et al. Scientists progress
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 kidney and brain expressed adapter protein (KIBRA), a postsynaptic scaffolding protein genetically linked to human memory performance, complexes with protein kinase Mzeta (PKMζ), anchoring the potentiating action of kinase to maintain long-term potentiation in the late (late) phase. -LTP) at the level of 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 LTP or PKMζ-independent memory that are maintained by compensatory PKCs in ζ knockout mice; thus, both agents require PKMζ for their effect. KIBRA-PKMζ complexes maintain 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.