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Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation.

Abstract

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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  • Authors+Show Affiliations

    ,

    Department of Neuroscience, Columbia University, New York, New York 10032, USA. as2619@columbia.edu

    , , , , , , ,

    Source

    Nature 472:7344 2011 Apr 28 pg 466-70

    MeSH

    Affect
    Aging
    Animals
    Antidepressive Agents
    Anxiety
    Apoptosis
    Cell Survival
    Cognition
    Conditioning, Classical
    Dentate Gyrus
    Exploratory Behavior
    Extinction, Psychological
    Fear
    Female
    Hippocampus
    Learning
    Long-Term Potentiation
    Male
    Memory
    Mice
    Mice, Knockout
    Mice, Transgenic
    Models, Neurological
    Neural Stem Cells
    Neurogenesis
    Neuronal Plasticity
    Physical Conditioning, Animal
    Synapses
    bcl-2-Associated X Protein

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    21460835

    Citation

    Sahay, Amar, et al. "Increasing Adult Hippocampal Neurogenesis Is Sufficient to Improve Pattern Separation." Nature, vol. 472, no. 7344, 2011, pp. 466-70.
    Sahay A, Scobie KN, Hill AS, et al. Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation. Nature. 2011;472(7344):466-70.
    Sahay, A., Scobie, K. N., Hill, A. S., O'Carroll, C. M., Kheirbek, M. A., Burghardt, N. S., ... Hen, R. (2011). Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation. Nature, 472(7344), pp. 466-70. doi:10.1038/nature09817.
    Sahay A, et al. Increasing Adult Hippocampal Neurogenesis Is Sufficient to Improve Pattern Separation. Nature. 2011 Apr 28;472(7344):466-70. PubMed PMID: 21460835.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation. AU - Sahay,Amar, AU - Scobie,Kimberly N, AU - Hill,Alexis S, AU - O'Carroll,Colin M, AU - Kheirbek,Mazen A, AU - Burghardt,Nesha S, AU - Fenton,André A, AU - Dranovsky,Alex, AU - Hen,René, Y1 - 2011/04/03/ PY - 2009/11/06/received PY - 2011/01/10/accepted PY - 2011/4/5/entrez PY - 2011/4/5/pubmed PY - 2011/6/22/medline SP - 466 EP - 70 JF - Nature JO - Nature VL - 472 IS - 7344 N2 - 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. SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/21460835/Increasing_adult_hippocampal_neurogenesis_is_sufficient_to_improve_pattern_separation_ L2 - http://dx.doi.org/10.1038/nature09817 DB - PRIME DP - Unbound Medicine ER -