In Flies, a Prion-Like Protein Helps Maintain Long-Term Memories

By Sarah Zhang | February 8, 2012 8:08 am

spacing is important

What’s the News: When prions or amyloids make the news, it’s usually because they cause mad cow disease or Alzheimer’sprions, after all, cause any proteins they touch to become as misfolded as they are, and amyloids, which are large clumps of wadded-together proteins, can jam the workings of cells.

But a new study in Cell suggests that a prion-like protein that forms amyloids has a normal, vital function in the brain. Far from being a memory destroyer, this protein, called CPEB, is necessary for long-term memory in fruit flies.

How the Heck:

  • To see where the protein resides in the brain, the researchers added a fluorescent tag to the fruit fly version of CPEB, which is called Orb2A. They observed that Orb2A formed amyloids at synapses, the junctions between neurons—a promising sign that it could be involved in memory.
  • To see whether Orb2A was actually necessary for memory, the researchers created fly mutants with a defective version of Orb2A. A single amino acid was changed, but that was enough to prevent the formation of amyloids.
  • It was also enough to disrupt the flies’ long-term memory, the team found. As a test of memory, flies had been taught to associate a particular smell with a squirt of sugar water, and at first, the mutant flies chose the reward-associated smell as just often as normal flies. 48 hours later, though, the mutants suddenly got much worse at the task.
  • Orb2A, thus, seems to be involved in maintaining memories over time.

What’s the Context:

  • The researchers already suspected that CPEB had a role in long-term memory, after a previous study in sea slugs suggested the two were linked: disrupting CPEB’s amyloids kept sea slugs’ neurons from undergoing long-term potentiation, which is similar to long-term memory. But it’s interesting to see that CPEB is also at work in the much more complex brains of fruit flies.
  • Over at The Frontal Cortex, Jonah Lehrer writes about a potential mechanism for CPEB in long-term memory. The prion-like protein marks any synapse involved in long-term memory, acting perhaps as a stop sign that prevents the connection from changing and the memory eroding.

The Future Holds:

  • How prions behave in various tissues and situations is a topic of active research—they were discovered only 20 years ago, and there’s a lot about them we don’t know. As this study suggests, it’s possible that certain prions have a perfectly normal function in the brain. Future studies will need to pin down the mechanism of how CPEB actually works at a synapse to preserve long-term memory.

Reference: Majumdar, et al. Critical Role of Amyloid-like Oligomers of Drosophila Orb2 in the Persistence of Memory. Cell 148, 515-529 (3 February 2012) DOI 10.1016/j.cell.2012.01.004

[via The Frontal Cortex]

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