concept of a human brain full of memories (© Studio_East - stock.adobe.com)
NEW YORK — Remember learning to ride a bike or your first trip to the zoo? These childhood memories often stick with us well into adulthood, but have you ever wondered how our brains manage to keep them intact for so long? A groundbreaking new study published in the journal Science Advances may have just cracked the code on long-term memory storage, and it all comes down to a microscopic “glue” in our brains.
The Secret Ingredient: KIBRA
An international team of researchers has discovered that a molecule called KIBRA (short for “kidney and brain expressed protein”) plays a crucial role in forming and maintaining long-term memories. Think of KIBRA as a special kind of glue that helps stick together other important memory-forming molecules in our brains.
“Previous efforts to understand how molecules store long-term memory focused on the individual actions of single molecules,” explains André Fenton, a professor of neural science at New York University and one of the study’s principal investigators, in a media release. “Our study shows how they work together to ensure perpetual memory storage.”
This discovery is more than just a cool science fact – it could have far-reaching implications for understanding and treating memory-related conditions.
“A firmer understanding of how we keep our memories will help guide efforts to illuminate and address memory-related afflictions in the future,” adds Todd Sacktor, a professor at SUNY Downstate Health Sciences University and one of the study’s principal investigators.
To understand why this discovery is so important, let's take a quick crash course in how our brains store memories. Our brains are made up of billions of neurons (nerve cells) that communicate with each other through connections called synapses. When we form a memory, certain synapses become stronger while others remain weak. This pattern of strong and weak connections forms a kind of “neural network” that represents the memory.
The problem is that the molecules in our synapses are constantly moving around, wearing out, and being replaced – kind of like how our bodies are always making new skin cells to replace old ones. So, how do our memories stay stable for years or even decades when the very building blocks are constantly changing? That's where KIBRA comes in.
Methodology
The research team, led by Fenton and Sacktor, conducted their study using laboratory mice. They focused on how KIBRA interacts with another crucial memory molecule called PKMzeta (protein kinase Mzeta). PKMzeta is super important for strengthening synapses in mammals, but it tends to break down after a few days.
Here's what they found:
- KIBRA acts as a “persistent synaptic tag” or glue that sticks to strong synapses (the ones involved in forming memories).
- KIBRA also sticks to PKMzeta, helping to keep it in place at these important synapses.
- This KIBRA-PKMzeta combo helps keep the synapses strong, even as individual molecules are replaced over time.
“During memory formation the synapses involved in the formation are activated—and KIBRA is selectively positioned in these synapses,” explains 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, attracting more newly made PKMzeta.”
Key Results
The team's experiments revealed some fascinating insights:
- Breaking the bond between KIBRA and PKMzeta actually erases old memories in mice.
- Adding more PKMzeta to the brain can enhance weak or faded memories – but only because KIBRA is there to guide it to the right synapses.
“The persistent synaptic tagging mechanism for the first time explains these results that are clinically relevant to neurological and psychiatric disorders of memory,” says Fenton, who is also on the faculty at NYU Langone Medical Center’s Neuroscience Institute.
Takeaways
By figuring out how our brains keep memories stable over long periods, researchers may be able to develop new treatments for conditions like Alzheimer's disease or post-traumatic stress disorder (PTSD).
Interestingly, this research also confirms an idea proposed way back in 1984 by Nobel Laureate Francis Crick. Crick suggested that the brain might use a mechanism similar to the philosophical concept of “Theseus's Ship” to maintain memories. In this ancient Greek thought experiment, a ship's planks are gradually replaced over time, but it remains the same ship.
“The persistent synaptic tagging mechanism we found is analogous to how new planks replace old planks to maintain Theseus’s Ship for generations, and allows memories to last for years even as the proteins maintaining the memory are replaced,” Sacktor concludes. “Francis Crick intuited this Theseus’s Ship mechanism, even predicting the role for 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.”
In other words, our brains use KIBRA and PKMzeta to keep our memories intact, even as the individual molecules are replaced over time – just like Theseus's Ship staying the same despite having all its parts replaced.
