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Ablating adult neurogenesis in the rat has no effect on spatial processing: evidence from a novel pharmacogenetic model

Abstract:
The function of adult neurogenesis in the rodent brain remains unclear. Ablation of adult born neurons has yielded conflicting results about emotional and cognitive impairments. One hypothesis is that adult neurogenesis in the hippocampus enables spatial pattern separation, allowing animals to distinguish between similar stimuli. We investigated whether spatial pattern separation and other putative hippocampal functions of adult neurogenesis were altered in a novel genetic model of neurogenesis ablation in the rat. In rats engineered to express thymidine kinase (TK) from a promoter of the rat glial fibrillary acidic protein (GFAP), ganciclovir treatment reduced new neurons by 98%. GFAP-TK rats showed no significant difference from controls in spatial pattern separation on the radial maze, spatial learning in the water maze, contextual or cued fear conditioning. Meta-analysis of all published studies found no significant effects for ablation of adult neurogenesis on spatial memory, cue conditioning or ethological measures of anxiety. An effect on contextual freezing was significant at a threshold of 5% (P = 0.04), but not at a threshold corrected for multiple testing. The meta-analysis revealed remarkably high levels of heterogeneity among studies of hippocampal function. The source of this heterogeneity remains unclear and poses a challenge for studies of the function of adult neurogenesis.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1371/journal.pgen.1003718

Authors


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Institution:
University of Oxford
Division:
MSD
Department:
Experimental Psychology
Role:
Author


Publisher:
Public Library of Science
Journal:
PLoS Genetics More from this journal
Volume:
9
Issue:
9
Pages:
e1003718
Publication date:
2013-09-05
Acceptance date:
2013-06-27
DOI:
EISSN:
1553-7404
ISSN:
1553-7390


Language:
English
Keywords:
UUID:
uuid:91dca6c3-95ac-4210-a21a-95ecf94e58ca
Local pid:
pubs:429113
Source identifiers:
429113
Deposit date:
2013-11-16

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