TY - JOUR
T1 - Neuronal circuitry mechanism regulating adult quiescent neural stem-cell fate decision
AU - Song, Juan
AU - Zhong, Chun
AU - Bonaguidi, Michael A.
AU - Sun, Gerald J.
AU - Hsu, Derek
AU - Gu, Yan
AU - Meletis, Konstantinos
AU - Huang, Z. Josh
AU - Ge, Shaoyu
AU - Enikolopov, Grigori
AU - Deisseroth, Karl
AU - Luscher, Bernhard
AU - Christian, Kimberly M.
AU - Ming, Guo Li
AU - Song, Hongjun
N1 - Funding Information:
Acknowledgements We thank L. H. Tsai for initial help in the study; members of the Song and Ming laboratories for discussion; H. Davoudi for help; and Q. Hussaini, Y. Cai and L. Liu for technical support. This work was supported by grants from the National Institutes of Health (NIH) (NS047344) to H.S., the NIH (NS048271, HD069184), the National Alliance for Research on Schizophrenia and Depression and the Adelson Medical Research Foundation to G.L.M., the NIH (MH089111) to B.L., the NIH (AG040209) andNewYork StateStem Cell ScienceandtheEllisonMedicalFoundation to G.E., and by postdoctoral fellowships from the Life Sciences Research Foundation to J.S. and from the Maryland Stem Cell Research Fund to J.S., C.Z. and K.C.
PY - 2012/9/6
Y1 - 2012/9/6
N2 - 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.
AB - 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.
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U2 - 10.1038/nature11306
DO - 10.1038/nature11306
M3 - Article
C2 - 22842902
AN - SCOPUS:84865801305
SN - 0028-0836
VL - 489
SP - 150
EP - 154
JO - Nature
JF - Nature
IS - 7414
ER -