Fly memory relies on protein chain

A family of proteins related to prions may play a critical role in the formation of memories, according to research from the Stowers Institute for Medicine. This family of proteins, called cytoplasmic polyadenylation element-binding proteins (CPEBs), forms chains between neurons in the brain that are critical for long-term memories.

In an article published in the journal Cell, Kausik Si, along with his colleagues and collaborators, detailed their findings about Orb2, a member of the CPEB family in Drosophila. By mutating the gene that encodes Orb2 to prevent Orb2 from forming chains, the researchers found that Orb2 forms short chains, called oligomers, between neurons for flies to retain information beyond 24 hours.

Memory formation in our brains relies on synapses, the connections between neurons, and is further dependent on the proteins that inhabit the synapses. CPEBs fall under a category of proteins capable of forming amyloids, which are fibrous layers of proteins known for their role in neurodegenerative diseases, such as Alzheimer's and Creutzfeldt-Jacob disease.

Creutzfeldt-Jacob dissease is caused by proteins called prions when they are improperly folded as a result of mutation. Prions can be transmitted through ingestion, as was the case with the Mad Cow Disease outbreak. Amyloids are insoluble and are rather tough in terms of their resistance to chemical breakdown. Orb2 relies on other proteins that are very similar to it in order to form oligomers. Researchers found that Orb2A, in particular, has a regulatory role in oligomer formation. To confirm that Orb2 had been forming oligomers and were not otherwise modified by the attachment of a different protein or chemical group in the flies, the researchers used antibodies to stain for these possible additions.

Staining did not return a positive result for the aforementioned contaminants. The Orb2 oligomers also demonstrated significant resistance to a variety of chemical solvents that the researchers applied, which would break down chains of other proteins.

In order to gauge the differences in memory performance between the normal fruit flies and those that carried mutations targeting Orb2A, researchers devised tasks to test long-term memory. One experiment involved suppressing the mating habits of male flies by exposing them to females that simply showed no interest in the male flies.

Results showed that the males would not attempt courtship for days as a learned behavior from this experience. However, the mutant flies soon forgot about the disinterest of the females and tried again after one or two days.

Another test involved pairing odors with a sugar reward. From this, the researchers noted that it would only take a two minute training session for the flies to learn what odors correlates to food. Although the mutant flies were able to remember the odors past 24 hours, their memory performance in this test weakened after 48 hours.

As a control in these experiments, the researchers injected the mutant flies with cDNA that contained the normal Orb2 gene. This restored normal memory function since fly neurons were able to utilize the cDNA to produce Orb2.

The results that Si and his group obtained in Drosophila follow similar experiments they had conducted in Aplysia, a genus of sea slugs. As a point for future directions in research, the group notes that the exact length of the Orb2 oligomers needed in between neurons has yet to be determined.