Adult hippocampal neurogenesis is functionally important for stress-induced social avoidance

Diane C. Lagace, Michael H. Donovan, Nathan A. Decarolis, Laure A. Farnbauch, Shveta Malhotra, Olivier Berton, Eric J. Nestler, Vaishnav Krishnan, Amelia J. Eisch

Research output: Contribution to journalArticle

203 Scopus citations

Abstract

The long-term response to chronic stress is variable, with some individuals developingmaladaptive 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 exploredwhether the susceptibility to stress-induced social avoidancewas related to changes in SGZ proliferation and neurogenesis. Immediately after social defeat, stressexposedmice (irrespectiveofwhether 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 stresswasalsonot altered.However,4weeks later, mice that displayed social avoidance hadmore surviving dentategyrus 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.

Original languageEnglish (US)
Pages (from-to)4436-4441
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number9
DOIs
StatePublished - Mar 2 2010

Keywords

  • Dentate gyrus
  • Nestin-GFP
  • Posttraumatic stress disorder
  • Social defeat
  • Subgranular zone

ASJC Scopus subject areas

  • General

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    Lagace, D. C., Donovan, M. H., Decarolis, N. A., Farnbauch, L. A., Malhotra, S., Berton, O., Nestler, E. J., Krishnan, V., & Eisch, A. J. (2010). Adult hippocampal neurogenesis is functionally important for stress-induced social avoidance. Proceedings of the National Academy of Sciences of the United States of America, 107(9), 4436-4441. https://doi.org/10.1073/pnas.0910072107