通过对小鼠进行研究，近日约翰霍普金斯大学的研究者揭示了，大脑中的干细胞可以如何对学习能力、记忆力和情绪进行调节来决定这些大脑中的剩余干细胞是否继续休眠还是产生新的脑细胞来作为补充。大脑干细胞可以在神经元之间“监听”其化学信息来发现什么对神经系统施压以及这些干细胞该如何行动。
doi:10.1038/nature11306
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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
Adult neurogenesis arises from neural stem cells within specialized niches1, 2, 3. 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 survival1, 3. 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 cells4, 5, 6, 7, 8, 9 (RGLs) respond tonically to the neurotransmitter γ-aminobutyric acid (GABA) by means of γ2-subunit-containing GABAA receptors. Clonal analysis9 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 division8. 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.
来源：生物谷
