Prion-like Protein Stabilizes Long-Term Memories in Mice

Prion-like Protein Stabilizes Long-Term Memories in Mice

Posted: August 17, 2015

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In research reported June 17th in the journal Neuron, scientists have shown that a protein called CPEB3 is critical for the stabilization and storage of long-term memories in mice. Three-time NARSAD Distinguished Investigator and BBRF Scientific Council member Eric Kandel, M.D., led the research. Also on the team is 2013 NARSAD Young Investigator Pierre Trifilieff, Ph.D.

CPEB3 is a “prion-like” protein. Prions––infectious, misshapen proteins best known for the devastation they cause––clump together and lead to brain damage in people and animals with mad cow disease and related conditions. Similar protein-clumping mechanisms may also contribute to neurodegenerative diseases including Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis. (Curiously, certain proteins with prion-like properties have an important role in the healthy brain.)

The new finding extends previous work showing that prion-like proteins are vital for the stabilization of long-term term memory in sea slugs and fruit flies. Although further work is needed to understand whether the same mechanism is at work in humans, humans do produce a protein similar to the mouse protein CPEB3.

Memories are stored in the connections between neurons, and proteins play a role in the long-term storage of the information. But since proteins degrade over time, scientists had wondered how a memory can persist long after a new experience triggers neurons to make memory-specific proteins. Prion-like proteins, which are self-perpetuating because they can convert normal proteins to their own misshapen form, appear to be the answer.

In their experiments with mice, Dr. Kandel's team showed that without the prion-like protein CPEB3, animals can form short-term memories, but the memories fade quickly. Mice without CPEB3 failed to retain their memories in a variety of tasks, such as navigating a maze after a training session.

Dr. Kandel and colleagues showed that CPEB3 production increases during learning. This increased production generates enough of the protein to enable clumping. These clumps, which persist indefinitely as they continue to recruit other CPEB3 molecules to form with them, trigger related neurons to produce the proteins needed to actively maintain the memory.

Read the abstract.

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