A Putative Biochemical Engram of Long-Term Memory.
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.
Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA; Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
Liying
L
Li
Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA; Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
Consuelo Perez
CP
Sanchez
Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA.
Brian D
BD
Slaughter
Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA.
Yubai
Y
Zhao
Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA.
Mohammed Repon
MR
Khan
Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA.
Jay R
JR
Unruh
Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA.
Boris
B
Rubinstein
Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA; Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA. Electronic address: ksi@stowers.org.
Kausik
K
Si
D000818:Animals; D030801:Animals, Genetically Modified; D004330:Drosophila / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005247:Feeding Behavior; D005786:Gene Expression Regulation / Q000502:physiology*; D057567:Memory, Long-Term / Q000502:physiology*; D012726:Sexual Behavior, Animal
D029721:Drosophila Proteins
amyloid; intrinsically disordered protein; memory engram; memory enhancement; persistence of memory; prion-like protein; synaptic protein synthesis; visualization of memory