GABAergic excitation promotes neuronal differentiation in adult hippocampal progenitor cells
GABAergic excitation promotes neuronal differentiation in adult hippocampal progenitor cells
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DOI：
10.1016/j.neuron.2005.08.023
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发表时间：
2005-09-15
期刊：
影响因子：
16.2
通讯作者：
Hisatsune, T
中科院分区：
文献类型：
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作者：
Tozuka, Y;Fukuda, S;Hisatsune, T
海马活动影响成人齿状回的神经发生；然而，人们对海马回路在此过程中的参与知之甚少。在成体齿状回的颗粒下区，神经发生涉及一系列分化步骤，从放射状胶质细胞样干细胞/祖细胞（1 型），到瞬时扩增神经元祖细胞（2 型），再到有丝分裂后神经元。在这项研究中，我们对来自巢蛋白 GFP 小鼠的新鲜海马切片中的祖细胞进行了 GFP 靶向记录，发现神经元祖细胞（2 型）接收来自海马回路的主动直接神经输入。该输入是 GABA 能的，但不是谷氨酸能的。由于 [Cl-](i) 升高，GABA 能输入使 2 型细胞去极化。这种兴奋引发了 [Ca2+](i) 和 NeuroD 表达的增加。使用 GABA(A)-R 激动剂进行的 BrdU 脉冲标记研究表明，这种 GABA 能兴奋可促进神经元分化。因此，海马祖细胞的 GABA 能输入似乎促进了活动依赖性神经元分化。
Hippocampal activity influences neurogenesis in the adult dentate gyrus; however, little is known about the involvement of the hippocampal circuitry in this process. In the subgranular zone of the adult dentate gyrus, neurogenesis involves a series of differentiation steps from radial glia-like stem/progenitor (type-1) cells, to transiently amplifying neuronal progenitor (type-2) cells, to postmitotic neurons. In this study, we conducted GFP-targeted recordings of progenitor cells in fresh hippocampal slices from nestin-GFP mice and found that neuronal progenitor (type-2) cells receive active direct neural inputs from the hippocampal circuitry. This input was GABAergic but not glutamatergic. The GABAergic inputs depolarized type-2 cells because of their elevated [Cl-](i). This excitation initiated an increase of [Ca2+](i) and the expression of NeuroD. A BrdU-pulse labeling study with GABA(A)-R agonists demonstrated the promotion of neuronal differentiation via this GABAergic excitation. Thus, it appears that GABAergic inputs to hippocampal progenitor cells promote activity-dependent neuronal differentiation.