Cited by 1,473Neurogenesis and neuroplasticity mechanismsStress Responses and CortisolMemory and Neural Mechanisms

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Adult hippocampal neurogenesis buffers stress responses and depressive behaviour

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Snyder, Jason S., Soumier, Amélie, Brewer, Michelle, Pickel, James, Cameron, Heather A.·2011·Nature

DOI 10.1038/nature10287PMC PMC3162077

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Abstract

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. In the hippocampus, a brain region densely populated with receptors for stress hormones, stress and glucocorticoids strongly inhibit adult neurogenesis. Decreased neurogenesis has been implicated in the pathogenesis of anxiety and depression, but direct evidence for this role is lacking. Here we show that adult-born hippocampal neurons are required for normal expression of the endocrine and behavioural components of the stress response. Using either transgenic or radiation methods to inhibit adult neurogenesis specifically, we find that glucocorticoid levels are slower to recover after moderate stress and are less suppressed by dexamethasone in neurogenesis-deficient mice than intact mice, consistent with a role for the hippocampus in regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Relative to controls, neurogenesis-deficient mice also showed increased food avoidance in a novel environment after acute stress, increased behavioural 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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Authors: Snyder, J. S., Soumier, A., Brewer, M., Pickel, J., & Cameron, H. A.
Affiliations: National Institutes of Health (US)
Corresponding author: Cameron, Heather A.
ORCID: Snyder, Jason S.
Soumier, Amélie
Brewer, Michelle
Pickel, James
Cameron, Heather A.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2011-08
Volume: 476
Issue: 7361
Pages: 458-461
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature10287
PMC: PMC3162077
OpenAlex: W2023343492
Cited by: 1,473
References: 34
Citations by year: 2026: 59 · 2025: 61 · 2024: 87 · 2023: 79 · 2022: 96 · 2021: 109 · 2020: 107 · 2019: 93 · 2018: 87 · 2017: 109 · 2016: 132 · 2015: 123 · 2014: 118 · 2013: 97 · 2012: 95
FWCI: 34.57
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Funders: National Science Foundation
GlaxoSmithKline
National Institutes of Health (Z01‐MH002784)
National Institute of Mental Health (ZIAMH002784)
Topics: Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords: adult hippocampal neurogenesis, stress response, depression, glucocorticoids, hypothalamic-pituitary-adrenal axis, dentate gyrus, anhedonia, food avoidance, behavioural despair, dexamethasone
MeSH terms: Animals, Behavior, Animal, Corticosterone, Depression, Dexamethasone, Glucocorticoids, Hippocampus, Hypothalamo-Hypophyseal System, Male, Mice, Inbred C57BL, Mice, Transgenic, Pituitary-Adrenal System, Receptors, Glucocorticoid, Restraint, Physical, Stress, Physiological, Swimming, Dentate Gyrus, Mice, Neurogenesis

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Adult hippocampal neurogenesis buffers stress responses and depressive behaviour

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