New Study Sheds Light on Why Some Memories Last a Lifetime

Scientists discover a molecule that acts as the brain’s memory glue, possibly explaining how memories remain despite cell turnover.

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A diary that never fades; that’s essentially what our brains are, thanks to a newly discovered molecular glue called KIBRA.

Scientists have discovered how this protein, along with its partner protein kinase M-zeta (PKMzeta), keeps our memories intact for decades—even as our brain cells continuously regenerate.

“Previous efforts to understand how molecules store long-term memory focused on the individual actions of single molecules,” André Fenton, a principal investigator of the study and professor of neural science at New York University, said in a statement. “Our study shows how they work together to ensure perpetual memory storage.”

How Our Brains Hold Onto Memories for Decades

Memories are stored in the brain through synapses, connections between neurons that strengthen with frequent signaling. These synapses form intricate neural networks responsible for encoding and retrieving information, allowing us to navigate daily life and shape our identities.

However, the molecules within synapses undergo constant renewal every few hours to days, raising the question: How do the memories encoded in these connections remain stable for decades?

A study on mice, recently published in Science Advances, explored kidney- and brain-expressed protein (KIBRA), found in both the kidneys and brain and known to correlate with human memory performance and cognition. The researchers focused on KIBRA’s interactions with other molecules, particularly PKMzeta. While PKMzeta is crucial for strengthening synapses, it naturally degrades within days.

The study uncovered KIBRA’s role as a “persistent synaptic tag” or glue, selectively attaching to strong synaptic connections and coupling with PKMzeta to preserve them. This targeting and tagging mechanism helps to stabilize specific neural connections that receive strong signals, ensuring that particular memories are stored for long-term retrieval while others fade away.

The strength of these signals during learning, along with processes involving KIBRA and PKMzeta, determines which memories are considered essential and stored based on how active the brain is and how meaningful the information is at the time, the researchers noted.

When a memory forms, “the synapses involved in the formation are activated—and KIBRA is selectively positioned in these synapses,” Dr. Todd Sacktor, co-author of the study and professor of pharmacology and neurology at State University of New York (SUNY) Downstate Health Sciences University, said in a statement.

“This allows the synapses to stick to newly made KIBRA, attracting more newly made PKMzeta,” Dr. Sacktor said, describing how these molecules work together in a continuous cycle.

Scientists Erase Memories in Mice

When researchers disrupted the bonds between KIBRA and PKMzeta in the brain, it affected the mice’s ability to retain spatial memories as tested through behavioral tasks. This demonstrates that these molecular interactions are vital for preserving certain types of long-term memories in the brain.

A 2021 study published in The European Journal of Neuroscience found that increasing PKMzeta can strengthen fading memories. This observation puzzled Mr. Fenton and Dr. Sacktor, who were involved in the study—until they discovered KIBRA’s synaptic tagging mechanism.

The ongoing process of synaptic tagging elucidates both of these results, which are crucial for understanding memory-related neurological and psychiatric disorders, according to Mr. Fenton.

Echoes of Sir Francis Crick’s Theory

The team’s discovery validates Sir Francis Crick’s 1984 hypothesis that molecular interactions in the brain sustain memories. Crick, a renowned British molecular biologist who co-discovered DNA’s double-helix structure in 1953, proposed this visionary concept. This idea compares memory’s resilience to the Ship of Theseus from Greek mythology. The Ship of Theseus, also known as Theseus’s Paradox, is a famous thought experiment that asks: If you replace every part of something over time, is it still the same thing?

Just as the ship persists by replacing its planks over time, memory endures despite constant molecular changes.

According to Dr. Sacktor, this allows memories to last for years even as the proteins maintaining them are replaced.

“A firmer understanding of how we keep our memories will help guide efforts to illuminate and address memory-related afflictions in the future,” he said.