Department of Neuroscience, Columbia University, New York, New York, USA.
Hippocampus. 2012 Sep;22(9):1795-808. doi: 10.1002/hipo.22013. Epub 2012 Mar 19.
The hippocampus is involved in segregating memories, an ability that utilizes the neural process of pattern separation and allows for cognitive flexibility. We evaluated a proposed role for adult hippocampal neurogenesis in cognitive flexibility using variants of the active place avoidance task and two independent methods of ablating adult-born neurons, focal X-irradiation of the hippocampus, and genetic ablation of glial fibrillary acidic protein positive neural progenitor cells, in mice. We found that ablation of adult neurogenesis did not impair the ability to learn the initial location of a shock zone. However, when conflict was introduced by switching the location of the shock zone to the opposite side of the room, irradiated and transgenic mice entered the new shock zone location significantly more than their respective controls. This impairment was associated with increased upregulation of the immediate early gene Arc in the dorsal dentate gyrus, suggesting a role for adult neurogenesis in modulating network excitability and/or synaptic plasticity. Additional experiments revealed that irradiated mice were also impaired in learning to avoid a rotating shock zone when it was added to an initially learned stationary shock zone, but were unimpaired in learning the identical simultaneous task variant if it was their initial experience with place avoidance. Impaired avoidance could not be attributed to a deficit in extinction or an inability to learn a new shock zone location in a different environment. Together these results demonstrate that adult neurogenesis contributes to cognitive flexibility when it requires changing a learned response to a stimulus-evoked memory.
海马体参与了记忆的分离，这种能力利用了模式分离的神经过程，使认知具有灵活性。我们使用主动回避任务的变体以及两种独立的方法来评估成年海马神经发生在认知灵活性中的作用，这两种方法是海马的局部 X 射线照射和胶质纤维酸性蛋白阳性神经祖细胞的基因消融，在小鼠中进行。我们发现，成年神经发生的消融并不会损害学习初始冲击区域位置的能力。然而，当通过将冲击区域的位置切换到房间的相反侧引入冲突时，照射和转基因小鼠进入新的冲击区域位置的次数明显多于各自的对照。这种损伤与背齿状回中即时早期基因 Arc 的上调增加有关，表明成年神经发生在调节网络兴奋性和/或突触可塑性方面的作用。进一步的实验表明，照射的小鼠在学习回避旋转冲击区域时也受到损伤，当将其添加到最初学习的固定冲击区域时，但在学习相同的同时任务变体时不受影响，如果这是他们最初的回避位置学习经验。回避受损不能归因于消退缺陷或在不同环境中学习新的冲击区域位置的能力丧失。这些结果表明，当需要改变对刺激诱发记忆的学习反应时，成年神经发生有助于认知灵活性。
