Department of Neurology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Proc Natl Acad Sci U S A. 2011 Mar 29;108(13):5437-42. doi: 10.1073/pnas.1015425108. Epub 2011 Mar 14.
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.
现在已经充分证实，啮齿动物海马齿状回的颗粒下区中的神经发生在整个成年期都在继续。在齿状回颗粒下区产生的神经前体细胞迁移到颗粒细胞层，在那里分化为称为齿状颗粒细胞的神经元。辐照或基因消融对神经发生的抑制已被证明会破坏齿状回的突触可塑性，并损害某些形式的海马体依赖的学习和记忆。使用最近开发的用于抑制神经发生的转基因小鼠模型，我们试图确定在年轻成年小鼠中消融神经发生对突触可塑性的长期影响。与先前的报告一致，我们发现，在消融后接近的时间点检查时，神经发生的消融导致齿状回长时程增强（LTP）的显著缺陷。然而，观察到的 LTP 缺陷不是永久性的。在完全没有神经发生的情况下，LTP 在 6 周内恢复。LTP 的恢复伴随着齿状回内的明显变化，包括增殖刚刚在消融之前的新生细胞的存活率增加，以及齿状回颗粒细胞的抑制性输入减少。这些发现表明，在年轻成年小鼠中长时间抑制神经发生会导致齿状回的结构和动力学发生广泛的代偿性变化，这些变化有助于恢复可塑性。
