title: Neuronal circuitry mechanism regulating adult quiescent neural stem-cell fate decision.
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 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.
authors: Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors: Juan
authors: J
authors: Song
authors: Chun
authors: C
authors: Zhong
authors: Michael A
authors: MA
authors: Bonaguidi
authors: Gerald J
authors: GJ
authors: Sun
authors: Derek
authors: D
authors: Hsu
authors: Yan
authors: Y
authors: Gu
authors: Konstantinos
authors: K
authors: Meletis
authors: Z Josh
authors: ZJ
authors: Huang
authors: Shaoyu
authors: S
authors: Ge
authors: Grigori
authors: G
authors: Enikolopov
authors: Karl
authors: K
authors: Deisseroth
authors: Bernhard
authors: B
authors: Luscher
authors: Kimberly M
authors: KM
authors: Christian
authors: Guo-li
authors: GL
authors: Ming
authors: Hongjun
authors: H
authors: Song
mesh_terms: D000818:Animals; D019070:Cell Lineage / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D018757:GABA Modulators / Q000494:pharmacology; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D007395:Interneurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology*; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010320:Parvalbumins / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013004:Somatostatin / Q000378:metabolism; D055153:Stem Cell Niche / Q000187:drug effects / Q000502:physiology; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018757:GABA Modulators; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D010320:Parvalbumins; D011963:Receptors, GABA-A; D014660:Vasoactive Intestinal Peptide; D013004:Somatostatin; D005680:gamma-Aminobutyric Acid