Adult hippocampal neurogenesis is functionally important for stress-induced social avoidance
Open accessAbstract
The long-term response to chronic stress is variable, with some individuals developing maladaptive functioning, although other "resilient" individuals do not. Stress reduces neurogenesis in the dentate gyrus subgranular zone (SGZ), but it is unknown if stress-induced changes in neurogenesis contribute to individual vulnerability. Using a chronic social defeat stress model, we explored whether the susceptibility to stress-induced social avoidance was related to changes in SGZ proliferation and neurogenesis. Immediately after social defeat, stress-exposed mice (irrespective of whether they displayed social avoidance) had fewer proliferating SGZ cells labeled with the S-phase marker BrdU. The decrease was transient, because BrdU cell numbers were normalized 24 h later. The survival of BrdU cells labeled before defeat stress was also not altered. However, 4 weeks later, mice that displayed social avoidance had more surviving dentate gyrus neurons. Thus, dentate gyrus neurogenesis is increased after social defeat stress selectively in mice that display persistent social avoidance. Supporting a functional role for adult-generated dentate gyrus neurons, ablation of neurogenesis via cranial ray irradiation robustly inhibited social avoidance. These data show that the time window after cessation of stress is a critical period for the establishment of persistent cellular and behavioral responses to stress and that a compensatory enhancement in neurogenesis is related to the long-term individual differences in maladaptive responses to stress.
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Adult neurogenesis in the hippocampus is necessary for stress-induced social avoidance and social cognition.
“Adult neurogenesis in the hippocampus has been shown to be necessary for stress-induced social avoidance (Lagace et al., 2010), as well as in social cognition (Garrett et al., 2015) (Figure 1C).”
From Adult neurogenesis, glia, and the extracellular matrix (2019) · cites this paper as Lagace et al., 2010
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- Authors
- Lagace, D. C., Donovan, M. H., DeCarolis, N. A., Farnbauch, L. A., Malhotra, S., Berton, O., Nestler, E. J., Krishnan, V., & Eisch, A. J.
- Affiliations
- University of Ottawa (CA)
- The University of Texas Southwestern Medical Center (US)
- University of Pennsylvania (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-02-22
- Volume
- 107
- Issue
- 9
- Pages
- 4436-4441
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2840117
- OpenAlex
- W2165546874
- Cited by
- 314
- References
- 41
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 11 · 2023: 17 · 2022: 14 · 2021: 18 · 2020: 19 · 2019: 28 · 2018: 24 · 2017: 13 · 2016: 26 · 2015: 27 · 2014: 27 · 2013: 15 · 2012: 23
- FWCI
- 7.28
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- National Institute of Mental Health (P50 MH66172, F31MH075457, P50MH066172, F31MH754572)
- National Institute on Drug Abuse (R21DA023701, K02DA023555, T32DA007290, R01DA016765)
- National Institute of Neurological Disorders and Stroke (F31NS064632)
- 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, chronic stress, social avoidance, social defeat stress, dentate gyrus, subgranular zone, stress resilience, individual differences, cranial irradiation, compensatory neurogenesis
- MeSH terms
- Animals, Avoidance Learning, Bromodeoxyuridine, Hippocampus, Male, Stress, Psychological, Signal Transduction, S Phase, Cell Death, Brain-Derived Neurotrophic Factor, Mice, Neurogenesis
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