Certain prion-like proteins are essential for creating and maintaining long-term memories, scientists, including one of Indian-origin, have found.
Prions are infectious agents composed of a protein in an abnormally folded form, and they cause damage to the structure of neural tissue.
Scientists at the Stowers Institute for Medical Research in US found that some prion-like proteins, however, can be precisely controlled so that they are generated only in a specific time and place.
These prion-like proteins are not involved in disease processes; rather, they are essential for creating and maintaining long-term memories.
"This protein is not toxic; it's important for memory to persist," said researcher Kausik Si, who led the study.
To ensure that long-lasting memories are created only in the appropriate neural circuits, Si said, the protein must be tightly regulated so that it adopts its prion-like form only in response to specific stimuli.
Si's lab is focused on finding the molecular alterations that encode a memory in specific neurons as it endures for the days, months, or years.
In 2012, Si's group demonstrated that in fruit flies, the prion-forming protein Orb2 is necessary for memories to persist. Flies that produce a mutated version of Orb2 that is unable to form prions learn new behaviours, but their memories are short-lived.
In the new study, Si wanted to find out how this process could be controlled so that memories form at the right time.
"We know that all experiences do not form long-term memory - somehow the nervous system has a way to discriminate. So if prion-formation is the biochemical basis of memory, it must be regulated," Si said.
"But prion formation appears to be random for all the cases we know of so far," Si added.
Si and his colleagues knew that Orb2 existed in two forms - Orb2A and Orb2B. Orb2B is widespread throughout the fruit fly's nervous system, but Orb2A appears only in a few neurons, at extremely low concentrations.
Once it is produced, Orb2A quickly falls apart; the protein has a half-life of only about an hour.
Researchers found that when a protein called TOB associates with Orb2A, it becomes much more stable, with a new half-life of 24 hours.
This step increases the prevalence of the prion-like state and explained how Orb2's conversion to the prion state can be confined in both time and space, researchers said.
Liying Li and Repon Mahammad Khan in the Department of Molecular and Integrative Physiology at the University of Kansas Medical Center, and Erica White- Grindley, Fengzhen Ren, Anita Saraf and Laurence Florens at the Stowers Institute for Medical Research also contributed to the work.
The study was published in the journal PLOS Biology.
