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首页> 美国卫生研究院文献>Frontiers in Cellular Neuroscience >Genetic control of adult neurogenesis: interplay of differentiation proliferation and survival modulates new neurons function and memory circuits
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Genetic control of adult neurogenesis: interplay of differentiation proliferation and survival modulates new neurons function and memory circuits

机译：成人神经发生的遗传控制：分化增殖和生存的相互作用调节新的神经元功能和记忆电路

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Within the hippocampal circuitry, the basic function of the dentate gyrus is to transform the memory input coming from the enthorinal cortex into sparse and categorized outputs to CA3, in this way separating related memory information. New neurons generated in the dentate gyrus during adulthood appear to facilitate this process, allowing a better separation between closely spaced memories (pattern separation). The evidence underlying this model has been gathered essentially by ablating the newly adult-generated neurons. This approach, however, does not allow monitoring of the integration of new neurons into memory circuits and is likely to set in motion compensatory circuits, possibly leading to an underestimation of the role of new neurons. Here we review the background of the basic function of the hippocampus and of the known properties of new adult-generated neurons. In this context, we analyze the cognitive performance in mouse models generated by us and others, with modified expression of the genes Btg2 (PC3/Tis21), Btg1, Pten, BMP4, etc., where new neurons underwent a change in their differentiation rate or a partial decrease of their proliferation or survival rate rather than ablation. The effects of these modifications are equal or greater than full ablation, suggesting that the architecture of circuits, as it unfolds from the interaction between existing and new neurons, can have a greater functional impact than the sheer number of new neurons. We propose a model which attempts to measure and correlate the set of cellular changes in the process of neurogenesis with the memory function.
机译：在海马电路中，齿状回的基本功能是将来自大脑皮层的记忆输入转换为稀疏的分类输出到CA3，从而分离相关的记忆信息。成年期间在齿状回中产生的新神经元似乎促进了这一过程，从而使间隔较近的记忆之间更好地分离（模式分离）。该模型的基础证据基本上是通过消融新成人产生的神经元来收集的。但是，这种方法不允许监视新神经元到存储电路中的整合，并且很可能设置在运动补偿电路中，这可能会导致低估新神经元的作用。在这里，我们审查海马的基本功能和新的成人生成的神经元的已知属性的背景。在这种情况下，我们分析了我们和其他人在小鼠模型中的认知功能，并修改了基因Btg2（PC3 / Tis21），Btg1，Pten，BMP4等的表达，其中新神经元的分化率发生了变化或其增殖或存活率的部分下降而不是消融。这些修饰的作用等于或大于完全消融，这表明电路的结构（由于其与现有神经元和新神经元之间的相互作用而展开）可能比纯粹数目的新神经元具有更大的功能影响。我们提出了一个模型，该模型试图测量和关联神经发生过程中的细胞变化与记忆功能。

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