title: 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.
authors.affiliation: The Wellcome Trust Centre for Human Genetics, The University of Oxford, Oxford, United Kingdom.
authors.forename: James O
authors.initials: JO
authors.lastname: Groves
authors.forename: Isla
authors.initials: I
authors.lastname: Leslie
authors.forename: Guo-Jen
authors.initials: GJ
authors.lastname: Huang
authors.forename: Stephen B
authors.initials: SB
authors.lastname: McHugh
authors.forename: Amy
authors.initials: A
authors.lastname: Taylor
authors.forename: Richard
authors.initials: R
authors.lastname: Mott
authors.forename: Marcus
authors.initials: M
authors.lastname: Munafò
authors.forename: David M
authors.initials: DM
authors.lastname: Bannerman
authors.forename: Jonathan
authors.initials: J
authors.lastname: Flint
mesh_terms: D000818:Animals; D001007:Anxiety / Q000503:physiopathology; D060825:Cognitive Dysfunction / Q000235:genetics* / Q000473:pathology; D003213:Conditioning, Psychological; D005239:Fear / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology*; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D055495:Neurogenesis / Q000235:genetics*; D009474:Neurons / Q000378:metabolism*; D010597:Pharmacogenetics; D051381:Rats; D013937:Thymidine Kinase / Q000235:genetics* / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D013937:Thymidine Kinase
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