Neuronal circuitry mechanism regulating adult quiescent neural stem-cell fate decision

Juan Song, Chun Zhong, Michael A. Bonaguidi, Gerald J. Sun, Derek Hsu, Yan Gu, Konstantinos Meletis, Z. Josh Huang, Shaoyu Ge, Grigori Enikolopov, Karl Deisseroth, Bernhard Luscher, Kimberly M. Christian, Guo Li Ming, Hongjun Song

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272 Scopus citations

Abstract

Adult neurogenesis arises from neural stem cells within specialized niches. Neuronal activity and experience, presumably acting on this local niche, regulate multiple stages of adult neurogenesis, from neural progenitor proliferation to new neuron maturation, synaptic integration and survival. It is unknown whether local neuronal circuitry has a direct impact on adult neural stem cells. Here we show that, in the adult mouse hippocampus, nestin-expressing radial glia-like quiescent neural stem cells (RGLs) respond tonically to the neurotransmitter 3-aminobutyric acid (GABA) by means of 3 2 -subunit-containing GABA A receptors. Clonal analysis of individual RGLs revealed a rapid exit from quiescence and enhanced symmetrical self-renewal after conditional deletion of 3 2. RGLs are in close proximity to terminals expressing 67-kDa glutamic acid decarboxylase (GAD67) of parvalbumin-expressing (PV +) interneurons and respond tonically to GABA released from these neurons. Functionally, optogenetic control of the activity of dentate PV + interneurons, but not that of somatostatin-expressing or vasoactive intestinal polypeptide (VIP)-expressing interneurons, can dictate the RGL choice between quiescence and activation. Furthermore, PV + interneuron activation restores RGL quiescence after social isolation, an experience that induces RGL activation and symmetrical division. Our study identifies a niche cellĝ€"signalĝ€" receptor trio and a local circuitry mechanism that control the activation and self-renewal mode of quiescent adult neural stem cells in response to neuronal activity and experience.

Original languageEnglish (US)
Pages (from-to)150-154
Number of pages5
JournalNature
Volume489
Issue number7414
DOIs
StatePublished - Sep 6 2012

All Science Journal Classification (ASJC) codes

  • General

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    Song, J., Zhong, C., Bonaguidi, M. A., Sun, G. J., Hsu, D., Gu, Y., Meletis, K., Huang, Z. J., Ge, S., Enikolopov, G., Deisseroth, K., Luscher, B., Christian, K. M., Ming, G. L., & Song, H. (2012). Neuronal circuitry mechanism regulating adult quiescent neural stem-cell fate decision. Nature, 489(7414), 150-154. https://doi.org/10.1038/nature11306