Neuron
Volume 70, Issue 5, 9 June 2011, Pages 908-923
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Article
Experience Dictates Stem Cell Fate in the Adult Hippocampus

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Summary

Adult hippocampal neurogenesis has been implicated in cognitive and emotional processes, as well as in response to antidepressant treatment. However, little is known about how the adult stem cell lineage contributes to hippocampal structure and function and how this process is modulated by the animal's experience. Here we perform an indelible lineage analysis and report that neural stem cells can produce expanding and persisting populations of not only neurons, but also stem cells in the adult hippocampus. Furthermore, the ratio of stem cells to neurons depends on experiences of the animal or the location of the stem cell. Surprisingly, social isolation facilitated accumulation of stem cells, but not neurons. These results show that neural stem cells accumulate in the adult hippocampus and that the stem cell-lineage relationship is under control of anatomic and experiential niches. Our findings suggest that, in the hippocampus, fate specification may act as a form of cellular plasticity for adapting to environmental changes.

Highlights

► Transgenic NesCreERT2 system enabled indelible lineage tracing from neural stem cells ► Fate mapping revealed that hippocampal stem cells are not quiescent, but accumulate ► X-irradiation blocks neurogenesis, but does not affect stem cell proliferation ► Social isolation promotes stem cell proliferation, but enrichment favors neurogenesis

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Present address: Department of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shingawa, Tokyo 142-8555, Japan

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These authors contributed equally to this work