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Environmental enrichment requires adult neurogenesis to facilitate the recovery from psychosocial stress.

Schloesser RJ, Lehmann M, Martinowich K, Manji HK, Herkenham M - Mol. Psychiatry (2010)

Bottom Line: It has been shown that production of new hippocampal neurons is necessary for amelioration of stress-induced behavioral changes by antidepressants in animal models of depression.Our data show two main findings.First, living in an enriched environment is highly effective in extinguishing submissive behavioral traits developed during chronic social stress, and second, these effects are critically dependent on adult neurogenesis, indicating that beneficial behavioral adaptations are dependent on intact adult neurogenesis.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular Pathophysiology, National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, MD 20892, USA.

ABSTRACT
The subgranular zone of the adult hippocampal dentate gyrus contains a pool of neural stem cells that continuously divide and differentiate into functional granule cells. It has been shown that production of new hippocampal neurons is necessary for amelioration of stress-induced behavioral changes by antidepressants in animal models of depression. The survival of newly born hippocampal neurons is decreased by chronic psychosocial stress and increased by exposure to enriched environments. These observations suggest the existence of a link between hippocampal neurogenesis, stress-induced behavioral changes, and the beneficial effects of enriched environment. To show causality, we subjected transgenic mice with conditionally suppressed neurogenesis to psychosocial stress followed by environmental enrichment. First, we showed that repeated social defeat coupled with chronic exposure to an aggressor produces robust and quantifiable indices of submissive and depressive-like behaviors; second, subsequent exposure to an enriched environment led to extinction of the submissive phenotype, while animals exposed to an impoverished environment retained the submissive phenotype; and third, enrichment was not effective in reversing the submissive and depressive-like behaviors in transgenic mice lacking neurogenesis. Our data show two main findings. First, living in an enriched environment is highly effective in extinguishing submissive behavioral traits developed during chronic social stress, and second, these effects are critically dependent on adult neurogenesis, indicating that beneficial behavioral adaptations are dependent on intact adult neurogenesis.

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Social exploration of an aggressor mouse is restored by EE only when neurogenesis is intact. Mice were tested in two social interaction tests. In the first, mice were allowed to explore an open field containing two wire cups, one empty and one containing an unfamiliar mouse. In the second test the unfamiliar mouse was replaced with the known aggressor from the SC living conditions. (a–d) No difference in behavior was observed between treatment groups when mice were exposed to an unfamiliar mouse. All groups preferred (Interaction Quotient Duration on Mouse [s]/Duration on Object [s]≅2) interacting with an unfamiliar mouse compared with interacting with an inanimate object. (e–h) However, when the aggressor was presented EE NG- mice as well as both IE groups spend significantly less time with the mouse than the EE Ctrl group (significant effect of treatment; F3,41=5.097, P<0.005, in f) The interaction quotient was also significantly higher in EE Ctrl as compared with all other groups (significant effect of treatment; F3,41=7.553, P<0.001, in h). Results are expressed as mean±s.e.m. n=11; *indicates significantly different (P<0.05) from all other treatment groups. One-way ANOVA followed by Tukey-Kramer post hoc test.
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fig5: Social exploration of an aggressor mouse is restored by EE only when neurogenesis is intact. Mice were tested in two social interaction tests. In the first, mice were allowed to explore an open field containing two wire cups, one empty and one containing an unfamiliar mouse. In the second test the unfamiliar mouse was replaced with the known aggressor from the SC living conditions. (a–d) No difference in behavior was observed between treatment groups when mice were exposed to an unfamiliar mouse. All groups preferred (Interaction Quotient Duration on Mouse [s]/Duration on Object [s]≅2) interacting with an unfamiliar mouse compared with interacting with an inanimate object. (e–h) However, when the aggressor was presented EE NG- mice as well as both IE groups spend significantly less time with the mouse than the EE Ctrl group (significant effect of treatment; F3,41=5.097, P<0.005, in f) The interaction quotient was also significantly higher in EE Ctrl as compared with all other groups (significant effect of treatment; F3,41=7.553, P<0.001, in h). Results are expressed as mean±s.e.m. n=11; *indicates significantly different (P<0.05) from all other treatment groups. One-way ANOVA followed by Tukey-Kramer post hoc test.

Mentions: To assess baseline social interaction, we measured the time the experimental mouse spent interacting with a wire mesh enclosure containing a similarly aged and sized C57BL/6J stranger mouse as opposed to an empty wire mesh enclosure (Supplementary Figure 4c). Mice can see, smell and explore the animal under the enclosure, but agonistic encounters are prevented (Supplementary Figure 4c). The experimental mouse is placed in the center of the arena and the time spent interacting with an enclosure containing a naive/stranger mouse or with an empty enclosure is scored. No differences between the four groups were observed in the time spent interacting with either the stranger-containing enclosure (Figure 5a and b) or with the empty enclosure (Figure 5a and c). Mice in all groups showed an interaction quotient (duration on stranger/duration on empty enclosure) at ∼2 (Figure 5d), indicating a preference for the stranger-containing enclosure as opposed to the empty enclosure.


Environmental enrichment requires adult neurogenesis to facilitate the recovery from psychosocial stress.

Schloesser RJ, Lehmann M, Martinowich K, Manji HK, Herkenham M - Mol. Psychiatry (2010)

Social exploration of an aggressor mouse is restored by EE only when neurogenesis is intact. Mice were tested in two social interaction tests. In the first, mice were allowed to explore an open field containing two wire cups, one empty and one containing an unfamiliar mouse. In the second test the unfamiliar mouse was replaced with the known aggressor from the SC living conditions. (a–d) No difference in behavior was observed between treatment groups when mice were exposed to an unfamiliar mouse. All groups preferred (Interaction Quotient Duration on Mouse [s]/Duration on Object [s]≅2) interacting with an unfamiliar mouse compared with interacting with an inanimate object. (e–h) However, when the aggressor was presented EE NG- mice as well as both IE groups spend significantly less time with the mouse than the EE Ctrl group (significant effect of treatment; F3,41=5.097, P<0.005, in f) The interaction quotient was also significantly higher in EE Ctrl as compared with all other groups (significant effect of treatment; F3,41=7.553, P<0.001, in h). Results are expressed as mean±s.e.m. n=11; *indicates significantly different (P<0.05) from all other treatment groups. One-way ANOVA followed by Tukey-Kramer post hoc test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2990187&req=5

fig5: Social exploration of an aggressor mouse is restored by EE only when neurogenesis is intact. Mice were tested in two social interaction tests. In the first, mice were allowed to explore an open field containing two wire cups, one empty and one containing an unfamiliar mouse. In the second test the unfamiliar mouse was replaced with the known aggressor from the SC living conditions. (a–d) No difference in behavior was observed between treatment groups when mice were exposed to an unfamiliar mouse. All groups preferred (Interaction Quotient Duration on Mouse [s]/Duration on Object [s]≅2) interacting with an unfamiliar mouse compared with interacting with an inanimate object. (e–h) However, when the aggressor was presented EE NG- mice as well as both IE groups spend significantly less time with the mouse than the EE Ctrl group (significant effect of treatment; F3,41=5.097, P<0.005, in f) The interaction quotient was also significantly higher in EE Ctrl as compared with all other groups (significant effect of treatment; F3,41=7.553, P<0.001, in h). Results are expressed as mean±s.e.m. n=11; *indicates significantly different (P<0.05) from all other treatment groups. One-way ANOVA followed by Tukey-Kramer post hoc test.
Mentions: To assess baseline social interaction, we measured the time the experimental mouse spent interacting with a wire mesh enclosure containing a similarly aged and sized C57BL/6J stranger mouse as opposed to an empty wire mesh enclosure (Supplementary Figure 4c). Mice can see, smell and explore the animal under the enclosure, but agonistic encounters are prevented (Supplementary Figure 4c). The experimental mouse is placed in the center of the arena and the time spent interacting with an enclosure containing a naive/stranger mouse or with an empty enclosure is scored. No differences between the four groups were observed in the time spent interacting with either the stranger-containing enclosure (Figure 5a and b) or with the empty enclosure (Figure 5a and c). Mice in all groups showed an interaction quotient (duration on stranger/duration on empty enclosure) at ∼2 (Figure 5d), indicating a preference for the stranger-containing enclosure as opposed to the empty enclosure.

Bottom Line: It has been shown that production of new hippocampal neurons is necessary for amelioration of stress-induced behavioral changes by antidepressants in animal models of depression.Our data show two main findings.First, living in an enriched environment is highly effective in extinguishing submissive behavioral traits developed during chronic social stress, and second, these effects are critically dependent on adult neurogenesis, indicating that beneficial behavioral adaptations are dependent on intact adult neurogenesis.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular Pathophysiology, National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, MD 20892, USA.

ABSTRACT
The subgranular zone of the adult hippocampal dentate gyrus contains a pool of neural stem cells that continuously divide and differentiate into functional granule cells. It has been shown that production of new hippocampal neurons is necessary for amelioration of stress-induced behavioral changes by antidepressants in animal models of depression. The survival of newly born hippocampal neurons is decreased by chronic psychosocial stress and increased by exposure to enriched environments. These observations suggest the existence of a link between hippocampal neurogenesis, stress-induced behavioral changes, and the beneficial effects of enriched environment. To show causality, we subjected transgenic mice with conditionally suppressed neurogenesis to psychosocial stress followed by environmental enrichment. First, we showed that repeated social defeat coupled with chronic exposure to an aggressor produces robust and quantifiable indices of submissive and depressive-like behaviors; second, subsequent exposure to an enriched environment led to extinction of the submissive phenotype, while animals exposed to an impoverished environment retained the submissive phenotype; and third, enrichment was not effective in reversing the submissive and depressive-like behaviors in transgenic mice lacking neurogenesis. Our data show two main findings. First, living in an enriched environment is highly effective in extinguishing submissive behavioral traits developed during chronic social stress, and second, these effects are critically dependent on adult neurogenesis, indicating that beneficial behavioral adaptations are dependent on intact adult neurogenesis.

Show MeSH
Related in: MedlinePlus