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

Publication ,  Journal Article
Song, J; Zhong, C; Bonaguidi, MA; Sun, GJ; Hsu, D; Gu, Y; Meletis, K; Huang, ZJ; Ge, S; Enikolopov, G; Deisseroth, K; Luscher, B; Ming, G-L ...
Published in: Nature
September 6, 2012

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 γ-aminobutyric acid (GABA) by means of γ2-subunit-containing GABAA receptors. Clonal analysis of individual RGLs revealed a rapid exit from quiescence and enhanced symmetrical self-renewal after conditional deletion of γ2. 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 cell–signal–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.

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Published In

Nature

DOI

EISSN

1476-4687

Publication Date

September 6, 2012

Volume

489

Issue

7414

Start / End Page

150 / 154

Location

England

Related Subject Headings

  • gamma-Aminobutyric Acid
  • Vasoactive Intestinal Peptide
  • Stem Cell Niche
  • Somatostatin
  • Signal Transduction
  • Receptors, GABA-A
  • Parvalbumins
  • Neuroglia
  • Neurogenesis
  • Neural Stem Cells
 

Citation

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Song, J., Zhong, C., Bonaguidi, M. A., Sun, G. J., Hsu, D., Gu, Y., … 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
Song, Juan, Chun Zhong, Michael A. Bonaguidi, Gerald J. Sun, Derek Hsu, Yan Gu, Konstantinos Meletis, et al. “Neuronal circuitry mechanism regulating adult quiescent neural stem-cell fate decision.Nature 489, no. 7414 (September 6, 2012): 150–54. https://doi.org/10.1038/nature11306.
Song J, Zhong C, Bonaguidi MA, Sun GJ, Hsu D, Gu Y, et al. Neuronal circuitry mechanism regulating adult quiescent neural stem-cell fate decision. Nature. 2012 Sep 6;489(7414):150–4.
Song, Juan, et al. “Neuronal circuitry mechanism regulating adult quiescent neural stem-cell fate decision.Nature, vol. 489, no. 7414, Sept. 2012, pp. 150–54. Pubmed, doi:10.1038/nature11306.
Song J, Zhong C, Bonaguidi MA, Sun GJ, Hsu D, Gu Y, Meletis K, Huang ZJ, Ge S, Enikolopov G, Deisseroth K, Luscher B, Christian KM, Ming G-L, Song H. Neuronal circuitry mechanism regulating adult quiescent neural stem-cell fate decision. Nature. 2012 Sep 6;489(7414):150–154.
Journal cover image

Published In

Nature

DOI

EISSN

1476-4687

Publication Date

September 6, 2012

Volume

489

Issue

7414

Start / End Page

150 / 154

Location

England

Related Subject Headings

  • gamma-Aminobutyric Acid
  • Vasoactive Intestinal Peptide
  • Stem Cell Niche
  • Somatostatin
  • Signal Transduction
  • Receptors, GABA-A
  • Parvalbumins
  • Neuroglia
  • Neurogenesis
  • Neural Stem Cells