Kleine Borgmann Felix B, Gräff Johannes, Mansuy Isabelle M, Toni Nicolas, Jessberger Sebastian
Laboratory of Neural Plasticity, Brain Research Institute, University of Zurich, Luxembourg Centre for Systems Biomedicine, University of Luxembourg.
Brain Research Institute, Laboratory of Neuroepigenetics, University of Zurich and Swiss Federal Institute of Technology Zurich, Department of Fundamental Neuroscience, University of Lausanne.
Matters Sel. 2016 Dec 29;2(12):201610000014. doi: 10.19185/matters.201610000014.
Dentate granule cells are born throughout life in the mammalian hippocampus. The integration of newborn neurons into the dentate circuit is activity-dependent, and structural data characterizing synapse formation suggested that the survival of adult-born granule cells is regulated by competition for synaptic partners. Here we tested this hypothesis by using a mouse model with genetically enhanced plasticity of mature granule cells through temporally controlled expression of a nuclear inhibitor of protein phosphatase (NIPP*). Using thymidine analogues and retrovirus-mediated cell labeling, we show that synaptic integration and subsequent survival of newborn neurons is decreased in NIPP*-expressing mice, suggesting that newborn neurons compete with preexisting granule cells for stable integration. The data presented here provides experimental evidence for a long-standing hypothesis and suggest cellular competition as a key mechanism regulating the integration and survival of newborn granule cells in the adult mammalian hippocampus.
齿状颗粒细胞在哺乳动物海马体中终生生成。新生神经元融入齿状回路的过程依赖于活动，且表征突触形成的结构数据表明，成年生成的颗粒细胞的存活受对突触伙伴的竞争调节。在此，我们通过一个小鼠模型来验证这一假设，该模型通过对蛋白磷酸酶核抑制剂（NIPP*）进行时间控制表达，使成熟颗粒细胞具有遗传增强的可塑性。利用胸腺嘧啶类似物和逆转录病毒介导的细胞标记，我们发现，在表达NIPP*的小鼠中，新生神经元的突触整合及随后的存活减少，这表明新生神经元与已有的颗粒细胞竞争稳定整合。此处呈现的数据为一个长期存在的假设提供了实验证据，并表明细胞竞争是调节成年哺乳动物海马体中新生颗粒细胞整合与存活的关键机制。
