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Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation
Open accessAbstract
Adult hippocampal neurogenesis is a unique form of neural circuit plasticity that results in the generation of new neurons in the dentate gyrus throughout life. Neurons that arise in adults (adult-born neurons) show heightened synaptic plasticity during their maturation and can account for up to ten per cent of the entire granule cell population. Moreover, levels of adult hippocampal neurogenesis are increased by interventions that are associated with beneficial effects on cognition and mood, such as learning, environmental enrichment, exercise and chronic treatment with antidepressants. Together, these properties of adult neurogenesis indicate that this process could be harnessed to improve hippocampal functions. However, despite a substantial number of studies demonstrating that adult-born neurons are necessary for mediating specific cognitive functions, as well as some of the behavioural effects of antidepressants, it is unknown whether an increase in adult hippocampal neurogenesis is sufficient to improve cognition and mood. Here we show that inducible genetic expansion of the population of adult-born neurons through enhancing their survival improves performance in a specific cognitive task in which two similar contexts need to be distinguished. Mice with increased adult hippocampal neurogenesis show normal object recognition, spatial learning, contextual fear conditioning and extinction learning but are more efficient in differentiating between overlapping contextual representations, which is indicative of enhanced pattern separation. Furthermore, stimulation of adult hippocampal neurogenesis, when combined with an intervention such as voluntary exercise, produces a robust increase in exploratory behaviour. However, increasing adult hippocampal neurogenesis alone does not produce a behavioural response like that induced by anxiolytic agents or antidepressants. Together, our findings suggest that strategies that are designed to increase adult hippocampal neurogenesis specifically, by targeting the cell death of adult-born neurons or by other mechanisms, may have therapeutic potential for reversing impairments in pattern separation and dentate gyrus dysfunction such as those seen during normal ageing.
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“Furthermore, new neurons, presumably through their unique electrophysiological properties and sparse connections to CA3 neurons (Amaral et al., 2007), have been found to participate in pattern separation (Clelland et al., 2009; Danielson et al., 2016; Sahay et al., 2011), the process of making similar neural inputs distinct.”
From Adult neurogenesis, glia, and the extracellular matrix (2019) · cites this paper as Sahay et al., 2011
In the citing paper
“Elimination or optogenetic silencing of adult-born neurons impairs pattern separation-like behaviors (Clelland et al., 2009; Danielson et al., 2016), while transgenic increases in adult neurogenesis enhance the ability of mice to distinguish between highly similar contexts (Sahay et al., 2011).”
From Adult neurogenesis, glia, and the extracellular matrix (2019) · cites this paper as Sahay et al., 2011
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“This primarily occurs through the role that neurogenesis plays in facilitating memory formation by dictating a computational mechanism known as pattern separation (Aimone et al., 2011; Sahay et al., 2011).”
From Aerobic Exercise as a Tool to Improve Hippocampal Plasticity and Function in Humans: Practical Implications for Mental Health Treatment (2016) · cites this paper as Sahay et al., 2011
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Metadata
- Authors
- Sahay, A., Scobie, K. N., Hill, A. S., O'Carroll, C. M., Kheirbek, M. A., Burghardt, N. S., Fenton, A. A., Dranovsky, A., & Hen, R.
- Affiliations
- Columbia University (US)
- New York State Psychiatric Institute (US)
- State University of New York (US)
- Corresponding author
- Sahay, Amar
- Hen, René
- ORCID
- Venue
- Nature
- Published
- 2011-04
- Volume
- 472
- Issue
- 7344
- Pages
- 466-470
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3084370
- OpenAlex
- W2146316688
- Cited by
- 1,567
- References
- 37
- Citations by year
- 2026: 46 · 2025: 73 · 2024: 82 · 2023: 83 · 2022: 97 · 2021: 100 · 2020: 116 · 2019: 101 · 2018: 109 · 2017: 134 · 2016: 132 · 2015: 128 · 2014: 134 · 2013: 106 · 2012: 85
- FWCI
- 38.02
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Mental Health (R01MH091844, K99MH086615, 1K99MH86615-01, K08MH079088, R01MH068542)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD007430)
- 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 hippocampal neurogenesis, pattern separation, dentate gyrus, adult-born neurons, neuronal survival, voluntary exercise, contextual fear conditioning, extinction learning, object recognition, spatial learning, anxiety disorders, antidepressants, neuroplasticity, cognitive enhancement
- MeSH terms
- Affect, Aging, Animals, Antidepressive Agents, Anxiety, Cell Survival, Cognition, Conditioning, Classical, Exploratory Behavior, Extinction, Psychological, Fear, Female, Hippocampus, Learning, Male, Memory, Mice, Transgenic, Models, Neurological, Neuronal Plasticity, Physical Conditioning, Animal, Synapses, Apoptosis, Long-Term Potentiation, Mice, Knockout, Dentate Gyrus, bcl-2-Associated X Protein, Mice, Neurogenesis, Neural Stem Cells
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