Research Points to Orb2 as a Physical Substrate for Memory Strength and Retention

Summary: Researchers report Orb2 plays a vital role in memory formation and retrieval in fruit flies. Additionally, JJJ2 appears to assist Orb2 in the formation of long term memory.

Source: Stowers Institute for Medical Research.

How do you remember what happened today in the weeks and months that follow? Researchers at the Stowers Institute for Medical Research have answered a piece of that question in a recent study.

“A simple way to think about our findings is that each experience leaves a stamp in the brain,” says Kausik Si, PhD, who led the study. “We have tried to address what such a stamp could be made of and what exactly it may be doing.”

Si and colleagues performed a detailed examination of Orb2, a protein previously implicated in long-term memory formation in fruit flies, at different stages of memory. A key characteristic of Orb2 is its prion-like ability to transform from one physical state to another and form clusters, or aggregates, under certain conditions.

Using tools that allow rapid and reversible inactivation of Orb2 protein in neurons, the researchers found that Orb2 can act as a physical substrate for encoding memory and serve as a molecular signature for long-term memory. They also discovered that a DnaJ family chaperone, JJJ2, assists Orb2 aggregation and enhances the formation of long-term memory.

Image shows Orb2 oligomer-dependent TEV protease reconstitution activity.
Using an activity reporter, Orb2 oligomer-dependent TEV protease reconstitution activity is seen in the fly brain. Areas of red and yellow indicate high courtship suppression (good memory). NeuroscienceNews image is credited to Liying Li, Si Lab Stowers Institute.

The findings were published in the December 5, 2016, issue of Current Biology and build upon earlier findings from the Si Lab that explain the molecular basis for the establishment of a memory trace.

“Using Drosophila as a model organism to study memory, we were able to exploit two different types of memories,” explains Liying Li, first author of the paper and a predoctoral researcher who is completing the research requirements for the Molecular and Integrative Physiology Graduate Program at the University of Kansas Medical Center in the Si Lab.

First, the researchers conducted a male courtship suppression memory experiment, which measures a male fruit fly’s ability to learn and retain memory of a female fruit fly’s interest in his courtship. In the second type of experiment, the researchers measured a fruit fly’s ability to associate one of two odors with a food source.

In these two types of memories, the researchers found three ways in which Orb2 seems to control the dynamics of memory. First, once memory is formed, it can be temporally inactivated and recover in an Orb2-dependent manner. Second, facilitation of Orb2 aggregation by the chaperone protein JJJ2 enhances the ability of fruit flies to form long-lasting memory. Finally, the amount of aggregated Orb2 predicts how stable the memory is. Together, these findings suggest that Orb2 is a constituent of a biochemical trace for memory and may help us understand what leads to loss of memory.

“Our results provide evidence that prion-like proteins play a positive role in memory formation and retention,” says Li. “Our work could potentially explain how functional, or good, protein aggregates differ from toxic aggregates. This could potentially help us find ways to regulate or control disease-forming prions.”

[divider]About this memory research article[/divider]

Other Stowers contributors include Consuelo Pérez Sánchez, Brian D. Slaughter, Ph.D., Yubai Zhao, Mohammed Repon Khan, Ph.D., Jay R. Unruh, Ph.D., and Boris Rubinstein, Ph.D.

Funding: This work was supported by the Stowers Institute for Medical Research and the National Institute of Mental Health of the National Institutes of Health (R01MH101440-01A1). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Source: Kim Bland – Stowers Institute for Medical Research
Image Source: NeuroscienceNews.com image is credited to Liying Li, Si Lab Stowers Institute.
Original Research: Abstract for “A Putative Biochemical Engram of Long-Term Memory” by Liying Li, Consuelo Perez Sanchez, Brian D. Slaughter, Yubai Zhao, Mohammed Repon Khan, Jay R. Unruh, Boris Rubinstein, and Kausik Si in Current Biology. Published online November 3 2016 doi:10.1016/j.cub.2016.09.054

[divider]Cite This NeuroscienceNews.com Article[/divider]

[cbtabs][cbtab title=”MLA”]Stowers Institute for Medical Research. “Research Points to Orb2 as a Physical Substrate for Memory Strength and Retention.” NeuroscienceNews. NeuroscienceNews, 4 December 2016.
<https://neurosciencenews.com/orb2-memory-retention-5671/>.[/cbtab][cbtab title=”APA”]Stowers Institute for Medical Research. (2016, December 4). Research Points to Orb2 as a Physical Substrate for Memory Strength and Retention. NeuroscienceNews. Retrieved December 4, 2016 from https://neurosciencenews.com/orb2-memory-retention-5671/[/cbtab][cbtab title=”Chicago”]Stowers Institute for Medical Research. “Research Points to Orb2 as a Physical Substrate for Memory Strength and Retention.” https://neurosciencenews.com/orb2-memory-retention-5671/ (accessed December 4, 2016).[/cbtab][/cbtabs]


Abstract

A Putative Biochemical Engram of Long-Term Memory

Highlights
•Orb2 is required for formation, maintenance, and expression of long-term memory
•Facilitation of Orb2 aggregation lowers the threshold for long-term memory formation
•Extent of Orb2 aggregation correlates with memory strength
•Orb2 aggregation can be used to visualize memory at the molecular level

Summary

How a transient experience creates an enduring yet dynamic memory remains an unresolved issue in studies of memory. Experience-dependent aggregation of the RNA-binding protein CPEB/Orb2 is one of the candidate mechanisms of memory maintenance. Here, using tools that allow rapid and reversible inactivation of Orb2 protein in neurons, we find that Orb2 activity is required for encoding and recall of memory. From a screen, we have identified a DNA-J family chaperone, JJJ2, which facilitates Orb2 aggregation, and ectopic expression of JJJ2 enhances the animal’s capacity to form long-term memory. Finally, we have developed tools to visualize training-dependent aggregation of Orb2. We find that aggregated Orb2 in a subset of mushroom body neurons can serve as a “molecular signature” of memory and predict memory strength. Our data indicate that self-sustaining aggregates of Orb2 may serve as a physical substrate of memory and provide a molecular basis for the perduring yet malleable nature of memory.

“A Putative Biochemical Engram of Long-Term Memory” by Liying Li, Consuelo Perez Sanchez, Brian D. Slaughter, Yubai Zhao, Mohammed Repon Khan, Jay R. Unruh, Boris Rubinstein, and Kausik Si in Current Biology. Published online November 3 2016 doi:10.1016/j.cub.2016.09.054

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