The Proteins that Allow for Long Term Memories

This piece, by Onno Berkan, was published on 10/01/24. The original story, by Simon Makin, was originally published in the Scientific American.

We have long wondered how memories work– they are the cornerstone of the human experience, they are what make you, you. As such, neuroscientists have long been looking for mechanisms to explain memories, and a near-20-year effort by SUNY professor Todd Sacktor makes a compelling case.

In a 2006 study, Sacktor showed that blocking the protein PKMzeta was found to erase place memories in rats. A follow up study released in June revealed that it is not just PKMzeta, but its interaction with another protein, KIBRA, that did the trick. This explained how PKMzeta, which only stays in cells for a short time, could have such long lasting effects. Synapses would get continually tagged by the interaction between KIBRA and PKMzeta and remain connected.

The theory is not without its holes, however, as it was found that mice genetically engineered to lack PKMzeta could still form long-term memories. This was explained by the presence of another molecule, PKCiota/lambda, which could step in when PKMzeta was inactive. This molecule was also blocked by the same PKMzeta blocker in the initial experiment, so it is within the rational confines of the theory.

Mice who had PKMzeta blocked from birth had elevated PKCiota/lambda, while those who had it blocked after did not. The low PKCiota/lambda group was found to suffer memory loss when only PKMzeta was inhibited, while the other saw minimal effects. Additionally, in 2011, Sacktor and colleagues found that boosting PKMzeta in rats enhanced old memories, which could have great clinical and therapeutic applications– namely suppressing and enhancing memories.

It should be noted that we still don’t know how to identify specific memories. Even if we did, it is unclear how well the enhanced PKMzeta method would work in humans. Scientists remain hopeful, though, and the discussion around the “memory molecule” remains open.

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