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Ablating Adult Neurogenesis in the Rat Has No Effect on Spatial Processing: Evidence from a Novel Pharmacogenetic Model

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  • James O Groves
  • Isla Leslie
  • Guo-Jen Huang
  • Stephen B McHugh
  • Amy Taylor
  • Richard Mott
  • Marcus Munafò
  • David M Bannerman
  • Jonathan Flint

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.Author Summary: Adult neurogenesis occurs in the rodent brain, but its function remains unclear. Current theories support the view that adult neurogenesis in the hippocampus supports pattern separation in the hippocampus, thereby allowing animals to distinguish between similar, overlapping inputs. However the effects of pharmacological, radiation and genetic ablation of adult neurogenesis on putative hippocampal functions have been inconsistent. We developed a novel genetic model to ablate adult neurogenesis in the rat. We found that we could reduce adult neurogenesis by 98%. Rats without adult neurogenesis showed no significant difference from controls in learning and memory tasks nor spatial pattern separation. We investigated the sources of heterogeneity in published results using a meta-analysis. The source of this heterogeneity remains unclear and poses a challenge for studies of the function of adult neurogenesis.

Suggested Citation

  • James O Groves & Isla Leslie & Guo-Jen Huang & Stephen B McHugh & Amy Taylor & Richard Mott & Marcus Munafò & David M Bannerman & Jonathan Flint, 2013. "Ablating Adult Neurogenesis in the Rat Has No Effect on Spatial Processing: Evidence from a Novel Pharmacogenetic Model," PLOS Genetics, Public Library of Science, vol. 9(9), pages 1-16, September.
    • Handle: RePEc:plo:pgen00:1003718
    DOI: 10.1371/journal.pgen.1003718
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    References listed on IDEAS

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    1. Henriette van Praag & Alejandro F. Schinder & Brian R. Christie & Nicolas Toni & Theo D. Palmer & Fred H. Gage, 2002. "Functional neurogenesis in the adult hippocampus," Nature, Nature, vol. 415(6875), pages 1030-1034, February.
    2. Jason S. Snyder & Amélie Soumier & Michelle Brewer & James Pickel & Heather A. Cameron, 2011. "Adult hippocampal neurogenesis buffers stress responses and depressive behaviour," Nature, Nature, vol. 476(7361), pages 458-461, August.
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