Bio-X Institutes, Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai 200240, China; Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599, USA.
Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599, USA.
Cell Stem Cell. 2017 Nov 2;21(5):604-617.e5. doi: 10.1016/j.stem.2017.10.003.
The quiescence of adult neural stem cells (NSCs) is regulated by local parvalbumin (PV) interneurons within the dentate gyrus (DG). Little is known about how local PV interneurons communicate with distal brain regions to regulate NSCs and hippocampal neurogenesis. Here, we identify GABAergic projection neurons from the medial septum (MS) as the major afferents to dentate PV interneurons. Surprisingly, dentate PV interneurons are depolarized by GABA signaling, which is in sharp contrast to most mature neurons hyperpolarized by GABA. Functionally, these long-range GABAergic inputs are necessary and sufficient to maintain adult NSC quiescence and ablating them leads to NSC activation and subsequent depletion of the NSC pool. Taken together, these findings delineate a GABAergic network involving long-range GABAergic projection neurons and local PV interneurons that couples dynamic brain activity to the neurogenic niche in controlling NSC quiescence and hippocampal neurogenesis.
成年神经干细胞 (NSCs) 的静止状态受齿状回 (DG) 内局部钙结合蛋白 (PV) 中间神经元的调节。目前尚不清楚局部 PV 中间神经元如何与远端脑区进行通讯，以调节 NSCs 和海马神经发生。在这里，我们确定了来自中隔 (MS) 的 GABA 能投射神经元是 DG 中 PV 中间神经元的主要传入神经元。令人惊讶的是，DG 中的 PV 中间神经元被 GABA 信号去极化，这与大多数成熟神经元被 GABA 超极化形成鲜明对比。功能上，这些长程 GABA 能输入对于维持成年 NSCs 的静止状态是必要且充分的，而破坏它们会导致 NSCs 激活和随后耗尽 NSCs 池。总之，这些发现描绘了一个涉及长程 GABA 能投射神经元和局部 PV 中间神经元的 GABA 能网络，该网络将动态脑活动与神经发生龛联系起来，以控制 NSCs 的静止和海马神经发生。
