Long term memories are maintained by prion like proteins

By John Murphy, MDLinx
Published January 5, 2016

Key Takeaways

Long-term memory depends on protein synthesis in the brain. Yet, how memories are maintained for long periods of time is not well understood. Research now shows that prion-like proteins—similar to the prions behind degenerative brain diseases such as mad cow disease in cattle and Creutzfeld-Jakob disease in humans—aggregate to maintain long-term memories in mice, and probably in other mammals.

In four papers published in Neuron and Cell Reports, investigators at Columbia University Medical Center (CUMC) show how prion-like proteins are critical for maintaining long-term memories in mice. “We find that both memory storage and its underlying synaptic plasticity are mediated by the increase in level and in the aggregation of the prion-like translational regulator CPEB3 (cytoplasmic polyadenylation element-binding protein),” the authors wrote.

While prions have been linked to a variety of neurodegenerative diseasesincluding Alzheimer’s, Parkinson’s, and Huntington’sfunctional prion proteins can play a physiological role in the cell and do not contribute to disease. The CUMC researchers first identified functional prions in the giant sea slug (Aplysia) and found they contribute to the maintenance of memory storage.

More recently, the CUMC team, led by Nobel laureate Eric Kandel, MD, searched for and found a similar protein in mice, CPEB3. In one of many experiments, the researchers challenged mice to repeatedly navigate a maze, allowing the animals to create a long-term memory. But when the researchers knocked out the animal’s CPEB3 gene two weeks after the memory was made, the memory disappeared.

The researchers then discovered how CPEB3 works inside the neurons to maintain long-term memories. “Like disease-causing prions, functional prions come in two varieties, a soluble form and a form that creates aggregates,” Dr. Kandel said. “When we learn something and form long-term memories, new synaptic connections are made, the soluble prions in those synapses are converted into aggregated prions. The aggregated prions turn on protein synthesis necessary to maintain the memory.”

As long as these aggregates are present, long-term memories persist. Prion aggregates renew themselves by continually recruiting newly made soluble prions into the aggregates. “This ongoing maintenance is crucial,” said Dr. Kandel. “It’s how you remember, for example, your first love for the rest of your life.”

A similar protein exists in humans, suggesting that the same mechanism is at work in the human brain, but more research is needed. “It’s possible that it has the same role in memory, but until this has been examined, we won’t know,” said Dr. Kandel.

“There are probably other regulatory components involved,” he added. “Long-term memory is a complicated process, so I doubt this is the only important factor.”

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