• A persistent bond between two proteins, PKMζ and KIBRA, is crucial for maintaining long-term memories by stabilizing synaptic connections.
• The KIBRA protein acts as a synaptic tag, guiding PKMζ to specific synapses involved in memory storage, addressing how specific memories are strengthened.
• This discovery helps reconcile the differing timescales of memory persistence and molecular turnover, suggesting memories endure because of the continuous bond between PKMζ and KIBRA.

A recent study published in Science Advances offers a potential explanation for how memories can persist for years, even decades, despite the constant turnover of molecules in the brain. Researchers discovered that a persistent bond between two proteins, protein kinase M zeta (PKMζ) and KIBRA, is associated with the strengthening of synapses, which are the connections between neurons. Synaptic strengthening is thought to be fundamental to memory formation, suggesting that as these proteins degrade, new ones take their place in a connected molecular swap that maintains the bond’s integrity and, therefore, the memory.

• What: Researchers discovered that a persistent bond between two proteins, PKMζ and KIBRA, is associated with the strengthening of synapses, which are the connections between neurons, and that this synaptic strengthening is fundamental to memory formation.
• Who: Key individuals involved include Todd Sacktor, André Fenton, Matteo Bernabo, Wayne Sossin, Karl Peter Giese, David Glanzman, and Panayiotis Tsokas. Key organizations include the State University of New York Downstate in Brooklyn, New York University, McGill University, King’s College London, and the University of California, Los Angeles.
• When: Francis Crick articulated the core question in 1984. Sacktor published findings on PKMζ in 1993. Sacktor and Fenton published their first paper in 2006. In 2013, studies cast doubt on PKMζ's role. In 2024, the Science Advances paper was published. The study about the PKMζ and KIBRA complex was conducted and published recently.
• Where: The research was conducted at the State University of New York Downstate in Brooklyn and involved collaborations with researchers at New York University and McGill University.

The discovery of the KIBRA-PKMζ protein interaction provides a significant advancement in understanding the molecular basis of long-term memory. The finding addresses the challenge of how memories persist despite the constant turnover of molecules in the brain. The fact that KIBRA acts as a synaptic tag guiding PKMζ offers further insight into the specificity of memory formation. While the study provides strong evidence for the role of this protein pair, the field acknowledges that other factors may also contribute to memory persistence. Alternative models, such as the molecular-encoding model, suggest that memory may be stored within molecules inside the neuron, although these do not negate synaptic strengthening.

How then is memory stored in the brain so that its trace is relatively immune to molecular turnover?

It’s the persistent association between two proteins that maintains the memory, rather than a protein that lasts by itself for the lifetime of the memory.

These experiments very nicely show that KIBRA is necessary for maintaining the activity of PKMζ at the synapse.

And that elegant answer is the KIBRA-PKMζ interacting story.

The discovery of the KIBRA-PKMζ protein interaction represents a significant step forward in understanding the molecular basis of long-term memory. The bond provides an elegant explanation for how memories can persist despite molecular turnover. While further research is necessary to explore other contributing factors and alternative models of memory storage, this finding offers a compelling response to the long-standing question of memory persistence.