NYC Gazette

A recent study published in the journal Science Advances by an international team of researchers has identified a biological explanation for the persistence of long-term memories. The research highlights the role of a molecule named KIBRA, which acts as a "glue" to other molecules, thus stabilizing memory formation.

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

Todd Sacktor, a professor at SUNY Downstate Health Sciences University and another principal investigator, emphasized the significance of this discovery: “A firmer understanding of how we keep our memories will help guide efforts to illuminate and address memory-related afflictions in the future.”

The study builds upon a concept introduced by Nobel Laureate Francis Crick regarding the brain's role in memory storage. Neurons store information through patterns of strong and weak synapses that determine neural network connectivity and function. However, because synaptic molecules are unstable and frequently replaced, it was unclear how memories could remain stable for years or even decades.

Using laboratory mice, researchers focused on KIBRA's interactions with protein kinase Mzeta (PKMzeta), an enzyme crucial for strengthening mammalian synapses but which degrades after a few days. Their findings revealed that KIBRA serves as a persistent synaptic tag or glue that binds to strong synapses and PKMzeta while avoiding weak synapses.

“During memory formation, the synapses involved are activated—and KIBRA is selectively positioned in these synapses,” explained Sacktor. “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.”

The experiments demonstrated that disrupting the bond between KIBRA and PKMzeta erases old memories. Previous research had shown that increasing PKMzeta randomly in the brain enhanced weak or faded memories—a finding now explained by KIBRA's persistent tagging mechanism.

“The persistent synaptic tagging mechanism for the first time explains these results that are clinically relevant to neurological and psychiatric disorders of memory,” observed Fenton.

The research reaffirms Francis Crick’s 1984 hypothesis likening memory retention despite cellular changes to Theseus’s Ship—a philosophical argument where new planks replace old ones to maintain continuity over time.

“The persistent synaptic tagging mechanism we found is analogous to how new planks replace old planks to maintain Theseus’s Ship for generations,” noted Sacktor. “Francis Crick intuited this Theseus’s Ship mechanism... But it took 40 years to discover that the components are KIBRA and PKMzeta.”

Contributors included researchers from McGill University in Canada, Germany’s University Hospital of Münster, and University of Texas Medical School at Houston. The work received support from various grants including those from the National Institutes of Health and Canada's Natural Sciences and Engineering Research Council Discovery.

About New York University

Founded in 1831, NYU is one of the world’s leading research universities with campuses globally including New York, Abu Dhabi, Shanghai among others. It offers diverse programs across numerous disciplines such as arts, sciences, law, medicine among others.

About SUNY Downstate Health Sciences University

Located in Brooklyn, Downstate Health Sciences University is part of SUNY system dedicated to health education, research, and patient care serving 2.7 million residents. It includes multiple esteemed educational institutions fostering innovation through biotechnology initiatives.

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