The role of adult hippocampal neurogenesis in brain health and disease

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Abstract

Adult neurogenesis in the dentate gyrus of the hippocampus is highly regulated by a number of environmental and cell-intrinsic factors to adapt to environmental changes. Accumulating evidence suggests that adult-born neurons may play distinct physiological roles in hippocampus-dependent functions such as memory encoding and mood regulation. In addition, several brain diseases, such as neurological diseases and mood disorders, have deleterious effects on adult hippocampal neurogenesis, and some symptoms of those diseases can be partially explained by the dysregulation of adult hippocampal neurogenesis. Here we review a possible link between the physiological functions of adult-born neurons and their roles in pathological conditions.

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Most cited references 211

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More hippocampal neurons in adult mice living in an enriched environment.

G Kempermann, H Kuhn, F H Gage (1997)

Neurogenesis occurs in the dentate gyrus of the hippocampus throughout the life of a rodent, but the function of these new neurons and the mechanisms that regulate their birth are unknown. Here we show that significantly more new neurons exist in the dentate gyrus of mice exposed to an enriched environment compared with littermates housed in standard cages. We also show, using unbiased stereology, that the enriched mice have a larger hippocampal granule cell layer and 15 per cent more granule cell neurons in the dentate gyrus.

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Adult hippocampal neurogenesis buffers stress responses and depressive behavior

Jason Snyder, Amélie Soumier, Michelle Brewer … (2011)

Summary Glucocorticoids are released in response to stressful experiences and serve many beneficial homeostatic functions. However, dysregulation of glucocorticoids is associated with cognitive impairments and depressive illness 1, 2 . In the hippocampus, a brain region densely populated with receptors for stress hormones, stress and glucocorticoids strongly inhibit adult neurogenesis 3 . Decreased neurogenesis has been implicated in the pathogenesis of anxiety and depression, but direct evidence for this role is lacking 4, 5 . Here we show that adult-born hippocampal neurons are required for normal expression of the endocrine and behavioral components of the stress response. Using transgenic and radiation methods to specifically inhibit adult neurogenesis, we find that glucocorticoid levels are slower to recover after moderate stress and are less suppressed by dexamethasone in neurogenesis-deficient mice compared with intact mice, consistent with a role for the hippocampus in regulation of the hypothalamic-pituitary-adrenal (HPA) axis 6, 7 . Relative to controls, neurogenesis-deficient mice showed increased food avoidance in a novel environment after acute stress, increased behavioral despair in the forced swim test, and decreased sucrose preference, a measure of anhedonia. These findings identify a small subset of neurons within the dentate gyrus that are critical for hippocampal negative control of the HPA axis and support a direct role for adult neurogenesis in depressive illness.

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Pattern separation in the dentate gyrus and CA3 of the hippocampus.

Jill K. Leutgeb, Stefan Leutgeb, May-Britt Moser … (2007)

Theoretical models have long pointed to the dentate gyrus as a possible source of neuronal pattern separation. In agreement with predictions from these models, we show that minimal changes in the shape of the environment in which rats are exploring can substantially alter correlated activity patterns among place-modulated granule cells in the dentate gyrus. When the environments are made more different, new cell populations are recruited in CA3 but not in the dentate gyrus. These results imply a dual mechanism for pattern separation in which signals from the entorhinal cortex can be decorrelated both by changes in coincidence patterns in the dentate gyrus and by recruitment of nonoverlapping cell assemblies in CA3.

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Author and article information

Journal

Journal ID (nlm-journal-id): 9607835

Journal ID (pubmed-jr-id): 20545

Journal ID (nlm-ta): Mol Psychiatry

Journal ID (iso-abbrev): Mol. Psychiatry

Title: Molecular psychiatry

ISSN (Print): 1359-4184

ISSN (Electronic): 1476-5578

Publication date Nihms-submitted: 1 February 2018

Publication date (Electronic): 20 April 2018

Publication date PMC-release: 20 October 2018

Electronic Location Identifier: 10.1038/s41380-018-0036-2

Affiliations

[1 ]Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA

Author notes

Correspondence should be addressed to: Dr. Fred H. Gage, Laboratory of Genetics – LOG-G, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, gage@ 123456salk.edu

[*]

These authors contributed equally to this work

Article

Manuscript ID: NIHMS939221

DOI: 10.1038/s41380-018-0036-2

PMC ID: 6195869

PubMed ID: 29679070

SO-VID: f09d36bf-2849-48ae-aa92-b789e0a9ee53

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The role of adult hippocampal neurogenesis in brain health and disease

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Most cited references 211

More hippocampal neurons in adult mice living in an enriched environment.

Adult hippocampal neurogenesis buffers stress responses and depressive behavior

Pattern separation in the dentate gyrus and CA3 of the hippocampus.

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