Ablating adult neurogenesis in the rat has no effect on spatial processing: evidence from a novel pharmacogenetic model
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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.
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Contradictory studies have found either no effect of reduced neurogenesis on hippocampal cognition or only on certain types of hippocampal cognitive tests, and one study found that absence of new neurons improves cognitive function.
“On the other hand, contradictory studies have found either no effect of reduced neurogenesis on hippocampal cognition (Groves et al., 2013; Saxe et al., 2006; Shors et al., 2002) or only on certain types of hippocampal cognitive tests (Shors et al., 2002). One study has even found that the absence of new neurons improves cognitive function (Saxe et al., 2007).”
From Adult neurogenesis, glia, and the extracellular matrix (2019) · cites this paper as Groves et al., 2013
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- Authors
- Groves, J. O., Leslie, I., Huang, G.-J., McHugh, S. B., Taylor, A., Mott, R., Munafò, M., Bannerman, D. M., & Flint, J.
- Affiliations
- Centre for Human Genetics (GB)
- Chang Gung University (TW)
- University of Oxford (GB)
- University of Bristol (GB)
- Corresponding author
- Bannerman, David M.
- Venue
- PLoS Genetics
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-09-05
- Volume
- 9
- Issue
- 9
- Pages
- e1003718
- ISSN
- 1553-7390 (ISSN-L)
- 1553-7404
- PMC
- PMC3764151
- OpenAlex
- W2089949016
- Cited by
- 121
- References
- 77
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 3 · 2023: 1 · 2022: 5 · 2021: 7 · 2020: 8 · 2019: 11 · 2018: 7 · 2017: 18 · 2016: 18 · 2015: 22 · 2014: 10 · 2013: 2
- FWCI
- 1.86
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Genetics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- UCL Discovery (University College London) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Explore Bristol Research (submittedVersion)
- Funders
- Wellcome Trust (089269, 083573, 084655, 087736, 089269/Z/09/Z, 090532, 083573/Z/07/Z, 090532/Z/09/Z, 090532/Z/09/, 083573/Z/07)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- adult neurogenesis, hippocampus, spatial pattern separation, spatial learning, spatial memory, fear conditioning, contextual fear, ganciclovir, anxiety
- MeSH terms
- Animals, Anxiety, Conditioning, Psychological, Fear, Glial Fibrillary Acidic Protein, Hippocampus, Memory, Neurons, Pharmacogenetics, Thymidine Kinase, Maze Learning, Rats, Neurogenesis, Cognitive Dysfunction
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