Document Detail

Posttraining ablation of adult-generated neurons degrades previously acquired memories.
MedLine Citation:
PMID:  22016545     Owner:  NLM     Status:  In-Data-Review    
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.
Maithe Arruda-Carvalho; Masanori Sakaguchi; Katherine G Akers; Sheena A Josselyn; Paul W Frankland
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  31     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  15113-27     Citation Subset:  IM    
Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Canada M5G 1X8, Department of Physiology, University of Toronto, Toronto, Canada M5S 1A8, and Institute of Medical Science, University of Toronto, Toronto, Canada M5S 1A8.
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