Adult hippocampal neurogenesis buffers stress responses and depressive behavior

By J. Snyder, A. Soumier, Michelle Brewer, J. Pickel, Heather A. Cameron. Nature, 2011

1,162 citations recorded by the source corpus.

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.

Subfields: Behavioral Neuroscience, Developmental Neuroscience, Social Psychology

View Paper: https://www.semanticscholar.org/paper/38688dee2bbd9a7417cbfa74dafaba8bccdfb61d

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In Behavioral Neuroscience

1. R. Hen
2. Melody V. Wu

In Developmental Neuroscience

1. Hongjun Song
2. Guo-li Ming
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4. Fred H. Gage
5. Allison M. Bond
6. B. R. Miller
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8. M. Kheirbek

In Social Psychology

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Citations in the corpus

• Adult Mammalian Neural Stem Cells and Neurogenesis: Five Decades Later (2015, background): “Excitement in this field continues with suggestions of additional functions of adult neurogenesis, such as buffering stress response (Snyder et al., 2011) and regulating ‘‘forgetting’’ or memory consolidation (Akers et al., 2014).”
• The current state of the neurogenic theory of depression and anxiety. (2015, result): “A second study found no effect on baseline behaviors, consistent with many other studies, but found that after an acute moderate stressor, mice with ablated AHN had significantly increased depression and anxiety-like behavior compared to mice with intact AHN [41].”
• Adult hippocampal neurogenesis, Rho kinase inhibition and enhancement of neuronal survival. (2013, background): “…to functional behaviours such as learning, spatial memory, anxiety, and depression (Gould et al., 1999, Shors et al., 2001, David et al., 2009, Revest et al., 2009, Snyder et al., 2011); we wished to determine whether alteration of neurogenesis by ROCK inhibition would affect these behaviours.”
• Functional Dissociation of Adult-Born Neurons Along the Dorsoventral Axis of the Dentate Gyrus (2014, methodology): “Five weeks after nonrandomized contextual discrimination, anxiety- and depression-related tests were performed Hippocampus immediately following 30 min of restraint (Snyder et al., 2011).”
• The Neurobiology of Anhedonia and Other Reward-Related Deficits (2011, background): “For example, decreased neurogenesis in the dentate gyrus reduced sucrose preference in mice [89] and reversed the therapeutic effects of fluoxetine, a selective serotonin reuptake inhibitor (SSRI), on separation stress-induced anhedonia in non-human primates [90].”
• Differential control of learning and anxiety along the dorso-ventral axis of the dentate gyrus (2013, background): “Furthermore, ablation of neurogenesis blocks certain behavioral effects of antidepressants and some responses to stress (David et al., 2009; Santarelli et al., 2003; Snyder et al., 2011; Surget et al., 2011).”