Posttraining ablation of adult-generated neurons degrades previously acquired memories

New neurons are continuously generated in the subgranular zone of the adult hippocampus and, once sufficiently mature, are thought to integrate into hippocampal memory circuits. However, whether they play an essential role in subsequent memory expression is not known. Previous studies have shown tha...

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Veröffentlicht in:The Journal of neuroscience 2011-10, Vol.31 (42), p.15113-15127
Hauptverfasser: Arruda-Carvalho, Maithe, Sakaguchi, Masanori, Akers, Katherine G, Josselyn, Sheena A, Frankland, Paul W
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container_end_page 15127
container_issue 42
container_start_page 15113
container_title The Journal of neuroscience
container_volume 31
creator Arruda-Carvalho, Maithe
Sakaguchi, Masanori
Akers, Katherine G
Josselyn, Sheena A
Frankland, Paul W
description New neurons are continuously generated in the subgranular zone of the adult hippocampus and, once sufficiently mature, are thought to integrate into hippocampal memory circuits. However, whether they play an essential role in subsequent memory expression is not known. Previous studies have shown that suppression of adult neurogenesis often (but not always) impairs subsequent hippocampus-dependent learning (i.e., produces anterograde effects). A major challenge for these studies is that these new neurons represent only a small subpopulation of all dentate granule cells, and so there is large potential for either partial or complete compensation by granule cells generated earlier on during development. A potentially more powerful approach to investigate this question would be to ablate adult-generated neurons after they have already become part of a memory trace (i.e., retrograde effects). Here we developed a diphtheria toxin-based strategy in mice that allowed us to selectively ablate a population of predominantly mature, adult-generated neurons either before or after learning, without affecting ongoing neurogenesis. Removal of these neurons before learning did not prevent the formation of new contextual fear or water maze memories. In contrast, removal of an equivalent population after learning degraded existing contextual fear and water maze memories, without affecting nonhippocampal memory. Ablation of these adult-generated neurons even 1 month after learning produced equivalent memory degradation in the water maze. These retrograde effects suggest that adult-generated neurons form a critical and enduring component of hippocampal memory traces.
doi_str_mv 10.1523/jneurosci.3432-11.2011
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subjects Animals
Antineoplastic Agents, Hormonal - pharmacology
Avoidance Learning - drug effects
Avoidance Learning - physiology
Behavior, Animal - drug effects
Bromodeoxyuridine
Calcium-Binding Proteins - metabolism
Cell Line, Transformed
Cell Proliferation - drug effects
Cell Survival - drug effects
Conditioning (Psychology) - drug effects
Dentate Gyrus - cytology
Diphtheria Toxin - pharmacology
Discrimination (Psychology) - drug effects
Discrimination (Psychology) - physiology
Estrogen Receptor alpha - metabolism
Fear - drug effects
Haplorhini
Heparin-binding EGF-like Growth Factor
Intercellular Signaling Peptides and Proteins - genetics
Intermediate Filament Proteins - genetics
Maze Learning - drug effects
Maze Learning - physiology
Membrane Transport Proteins - genetics
Memory - drug effects
Memory - physiology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Microfilament Proteins - metabolism
Microtubule-Associated Proteins - metabolism
Naphthalenes
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Nestin
Neurogenesis - drug effects
Neurogenesis - genetics
Neurogenesis - physiology
Neurons - drug effects
Neurons - physiology
Neuropeptides - metabolism
Oxepins
Space Perception - drug effects
Space Perception - physiology
Tamoxifen - pharmacology
Taste - drug effects
Taste - genetics
title Posttraining ablation of adult-generated neurons degrades previously acquired memories
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