title: The Persistence of Hippocampal-Based Memory Requires Protein Synthesis Mediated by the Prion-like Protein CPEB3.
abstract: Consolidation of long-term memories depends on de novo protein synthesis. Several translational regulators have been identified, and their contribution to the formation of memory has been assessed in the mouse hippocampus. None of them, however, has been implicated in the persistence of memory. Although persistence is a key feature of long-term memory, how this occurs, despite the rapid turnover of its molecular substrates, is poorly understood. Here we find that both memory storage and its underlying synaptic plasticity are mediated by the increase in level and in the aggregation of the prion-like translational regulator CPEB3 (cytoplasmic polyadenylation element-binding protein). Genetic ablation of CPEB3 impairs the maintenance of both hippocampal long-term potentiation and hippocampus-dependent spatial memory. We propose a model whereby persistence of long-term memory results from the assembly of CPEB3 into aggregates. These aggregates serve as functional prions and regulate local protein synthesis necessary for the maintenance of long-term memory.
authors.affiliation: Department of Neuroscience, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
authors.forename: Luana
authors.initials: L
authors.lastname: Fioriti
authors.affiliation: Department of Neuroscience, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
authors.forename: Cory
authors.initials: C
authors.lastname: Myers
authors.affiliation: Department of Neuroscience, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
authors.forename: Yan-You
authors.initials: YY
authors.lastname: Huang
authors.affiliation: Department of Neuroscience, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neuroscience, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA; Howard Hughes Medical Institute, New York, NY 10032, USA.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Stephan
authors.affiliation: Department of Neuroscience, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
authors.forename: Pierre
authors.initials: P
authors.lastname: Trifilieff
authors.affiliation: Department of Neuroscience, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA; Howard Hughes Medical Institute, New York, NY 10032, USA.
authors.forename: Luca
authors.initials: L
authors.lastname: Colnaghi
authors.affiliation: Department of Neuroscience, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA; Howard Hughes Medical Institute, New York, NY 10032, USA.
authors.forename: Stylianos
authors.initials: S
authors.lastname: Kosmidis
authors.affiliation: Department of Neuroscience, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
authors.forename: Bettina
authors.initials: B
authors.lastname: Drisaldi
authors.affiliation: Department of Neuroscience, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
authors.forename: Elias
authors.initials: E
authors.lastname: Pavlopoulos
authors.affiliation: Department of Neuroscience, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA; Howard Hughes Medical Institute, New York, NY 10032, USA; Kavli Institute for Brain Science, New York, NY 10032, USA. Electronic address: erk5@columbia.edu.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Kandel
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics; D003213:Conditioning, Psychological / Q000502:physiology; D005106:Exploratory Behavior / Q000502:physiology; D005239:Fear / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D066298:In Vitro Techniques; D008124:Locomotion / Q000235:genetics; D017774:Long-Term Potentiation / Q000187:drug effects / Q000235:genetics; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000502:physiology; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D011930:Reaction Time / Q000235:genetics / Q000502:physiology
chemical_list: C477603:Cpeb3 protein, mouse; D016601:RNA-Binding Proteins; D018698:Glutamic Acid; D010751:Phosphopyruvate Hydratase