Research reveals ‘molecular glue’ that helps form and stabilize memories

Whether it’s our first visit to a zoo or when we learned to ride a bike, we have memories from childhood that last well into our adult years. But what explains why these memories last almost a lifetime?

A survey in the journal Scientific progressconducted 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, which 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 alleviate 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 lead 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 the synapses are unstable, constantly moving around in the neurons, worn out and replaced within hours to days, which begs the question: how then can memories remain stable for years to 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 at these synapses,” explained Sacktor, a 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, which attracts more newly made PKMzeta.”

More specifically, their experiments in the Scientific progress Research shows that severing the KIBRA-PKMzeta tie erases old memories.

Previous research had shown that randomly increasing PKMzeta in the brain strengthens weak or faded memories, which was mysterious because it should have done the opposite by acting in random locations. But the persistent synaptic tagging by KIBRA explains why the extra PKMzeta improved memory, acting only at the KIBRA-tagged sites.

“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 authors of the article 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 constant cellular and molecular changes, is a ship of Theseus mechanism – taken from a philosophical argument arising from Greek mythology, in which new planks replaced the old ones to maintain the ship of Theseus for a long time. year.

“The persistent synaptic tagging mechanism we found is analogous to how new planks replace old planks to maintain the Ship of Theseus for generations, and ensures that memories last for years even if the proteins that maintain memory are replaced,” says Sacktor.

“Francis Crick intuitively sensed this mechanism of Theseus’ ship and even predicted the role of a protein kinase. But it took 40 years to discover that the components are KIBRA and PKMzeta and to work out the mechanism of their interaction.”

Researchers from Canada’s McGill University, the University of Münster Hospital in Germany and the University of Texas Medical School in Houston also participated in the study.