Hippocampal neurogenesis confers stress resilience by inhibiting the ventral dentate gyrus
Open accessAbstract
Adult neurogenesis in the dentate gyrus of the hippocampus is highly regulated by environmental influences, and functionally implicated in behavioural responses to stress and antidepressants 1-4. However, how adult-born neurons regulate dentate gyrus information processing to protect from stress-induced anxiety-like behaviour is unknown. Here we show in mice that neurogenesis confers resilience to chronic stress by inhibiting the activity of mature granule cells in the ventral dentate gyrus (vDG), a subregion that is implicated in mood regulation. We found that chemogenetic inhibition of adult-born neurons in the vDG promotes susceptibility to social defeat stress, whereas increasing neurogenesis confers resilience to chronic stress. By using in vivo calcium imaging to record neuronal activity from large cell populations in the vDG, we show that increased neurogenesis results in a decrease in the activity of stress-responsive cells that are active preferentially during attacks or while mice explore anxiogenic environments. These effects on dentate gyrus activity are necessary and sufficient for stress resilience, as direct silencing of the vDG confers resilience whereas excitation promotes susceptibility. Our results suggest that the activity of the vDG may be a key factor in determining individual levels of vulnerability to stress and related psychiatric disorders.
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A few studies provide evidence that absence of neurogenesis elicits depressive-like symptoms in rodents, but most studies find that absent neurogenesis is not sufficient to induce a depressive phenotype, although it is required in mice for the behavioral effects of antidepressants.
“A few studies provide evidence that the absence of neurogenesis elicits depressive like symptoms in rodents123, 124, but most studies find that absent neurogenesis is not sufficient to induce a depressive phenotype125 although it is required in mice for the behavioral effects of antidepressants118, 126.”
From Dysregulation of adult hippocampal neuroplasticity in major depression: Pathogenesis and therapeutic implications (2022) · cites this paper as [126]
Adult neurogenesis in the hippocampus seems to provide resilience to stress-induced anxiety.
“Adult neurogenesis in the hippocampus seems to provide resilience to stress-induced anxiety (Anacker et al., 2018; Hill et al., 2015; Snyder et al., 2011).”
From Adult neurogenesis, glia, and the extracellular matrix (2019) · cites this paper as Anacker et al., 2018
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- Authors
- Anacker, C., Luna, V. M., Stevens, G. S., Millette, A., Shores, R., Jimenez, J. C., Chen, B., & Hen, R.
- Affiliations
- Research Foundation For Mental Hygiene (US)
- Corresponding author
- Anacker, Christoph
- Hen, René
- Venue
- Nature
- Published
- 2018-06-27
- Volume
- 559
- Issue
- 7712
- Pages
- 98-102
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6118212
- OpenAlex
- W2811270075
- Cited by
- 605
- References
- 38
- Citations by year
- 2026: 49 · 2025: 74 · 2024: 72 · 2023: 78 · 2022: 69 · 2021: 88 · 2020: 79 · 2019: 63 · 2018: 14 · 2012: 1
- FWCI
- 22.42
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- 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)
- Funders
- National Institutes of Health (1s10od018464-01)
- National Institute on Aging (K01AG054765, R01AG043688)
- National Institute of Mental Health (R37MH068542, R01MH083862, K99MH108719, T32MH015174, R01MH068542)
- National Institute of Neurological Disorders and Stroke (R01NS081203)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- adult neurogenesis, hippocampus, ventral dentate gyrus, stress resilience, chronic stress, social defeat stress, anxiety-like behavior, granule cells, chemogenetic inhibition, neuronal activity, mood regulation, psychiatric vulnerability
- MeSH terms
- Affect, Animals, Calcium, Chronic Disease, Male, Stress, Psychological, Dentate Gyrus, Mice, Neurogenesis, Resilience, Psychological
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