Compensatory network changes in the dentate gyrus restore long-term potentiation following ablation of neurogenesis in young-adult mice
Compensatory network changes in the dentate gyrus restore long-term potentiation following ablation of neurogenesis in young-adult mice
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DOI：
10.1073/pnas.1015425108
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发表时间：
2011-03-29
影响因子：
11.1
通讯作者：
Murphy, Geoffrey G.
中科院分区：
文献类型：
--
作者：
Singer, Benjamin H.;Gamelli, Amy E.;Murphy, Geoffrey G.
现在已经确定，啮齿动物海马齿状回亚颗粒带的神经发生持续整个成年期。出生在齿状亚颗粒带的神经母细胞迁移到颗粒细胞层，在那里它们分化成被称为齿状颗粒细胞的神经元。通过照射或基因消融抑制神经发生已被证明会破坏齿状回的突触可塑性并损害海马依赖的某些形式的学习和记忆。利用最近开发的抑制神经发生的转基因小鼠模型，我们试图确定切除神经发生对年轻成年小鼠突触可塑性的长期影响。与之前的报道一致，我们发现神经发生的消融导致齿状回长期增强（LTP）的显著缺陷，当在消融的近端检查时。然而，观察到的LTP缺陷并不是永久性的。齿状回LTP在6周内恢复，这种恢复发生在完全没有神经发生的情况下。LTP的恢复伴随着齿状回内的显著变化，包括消融前增殖的新生细胞存活率的增加和齿状回颗粒细胞抑制性输入的减少。这些发现表明，长期抑制年轻成年小鼠的神经发生导致齿状回结构和动力学的广泛代偿性变化，这些变化具有恢复可塑性的功能。
It is now well established that neurogenesis in the rodent subgranular zone of the hippocampal dentate gyrus continues throughout adulthood. Neuroblasts born in the dentate subgranular zone migrate into the granule cell layer, where they differentiate into neurons known as dentate granule cells. Suppression of neurogenesis by irradiation or genetic ablation has been shown to disrupt synaptic plasticity in the dentate gyrus and impair some forms of hippocampus-dependent learning and memory. Using a recently developed transgenic mouse model for suppressing neurogenesis, we sought to determine the long-term impact of ablating neurogenesis on synaptic plasticity in young-adult mice. Consistent with previous reports, we found that ablation of neurogenesis resulted in significant deficits in dentate gyrus long-term potentiation (LTP) when examined at a time proximal to the ablation. However, the observed deficits in LTP were not permanent. LTP in the dentate gyrus was restored within 6 wk and this recovery occurred in the complete absence of neurogenesis. The recovery in LTP was accompanied by prominent changes within the dentate gyrus, including an increase in the survival rate of newborn cells that were proliferating just before the ablation and a reduction in inhibitory input to the granule cells of the dentate gyrus. These findings suggest that prolonged suppression of neurogenesis in young-adult mice results in wide-ranging compensatory changes in the structure and dynamics of the dentate gyrus that function to restore plasticity.