Drosophila CPEB, Orb2, a Putative Biochemical Engram of Long-term Memory

How a transient experience creates an enduring yet dynamic memory remains a fundamental 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 I find that Orb2 activity is required for encoding and recall of memory. Blocking the Orb2 oligomerization process by interfering with the protein phosphorylation pathway or expressing an anti-amyloidogenic peptide impairs long-term memory. Facilitating Orb2 aggregation by a DNA-J family chaperone, JJJ2, enhances the animal’s capacity to form long-term memory. Finally, I have developed tools to visualize training-dependent aggregation of Orb2. I find that aggregated Orb2 in subset of mushroom body neurons can serve as a “molecular signature” of memory and predict memory strength. My 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.

Grantor dc:publisher

University of Kansas

Year dc:date.issued

2017

Author dc:creator

• Li, Liying

Advisors dc:contributor.advisor

• Si, Kausik
• Cheney, Paul

• Neurosciences
• Molecular biology
• CPEB
• engram
• long-term memory
• prion-like molecule

Statement dc:rights

• Copyright held by the author.

Language dc:language.iso

en

Dc Identifier Other

http://dissertations.umi.com/ku:15506

OAI identifier oai:identifier

oai:kuscholarworks.ku.edu:1808/26893