Paradoxical effects of learning the Morris water maze on adult hippocampal neurogenesis in mice may be explained by a combination of stress and physical activity
Paradoxical effects of learning the Morris water maze on adult hippocampal neurogenesis in mice may be explained by a combination of stress and physical activity
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DOI：
10.1111/j.1601-183x.2005.00129.x
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发表时间：
2006-02-01
影响因子：
2.5
通讯作者：
Kempermann, G
中科院分区：
文献类型：
--
作者：
Ehninger, D;Kempermann, G
大鼠海马依赖性学习与成年海马神经发生关系的研究表明，学习对神经发生有直接的调节作用，而小鼠的类似研究没有发现这种因果关系。我们在此报告，与未训练的动物（CTR）相比，在Morris水迷宫的隐藏（HID）或提示（VIS）中训练的小鼠，brdu阳性细胞和其他成年海马神经发生的测量结果显著减少。特别是，处于神经元发育晚期的细胞导致了这种减少，而与CTR相比，早期祖细胞（2型细胞）在HID中没有减少，但在VIS中减少。在HID和VIS中，2型细胞的差异调节可能是由不同程度的身体活动引起的，因为时间约束的对照组与HID没有差异，并且据报道，2型细胞构成了主要对身体活动有反应的增殖性齿状回群体。水迷宫训练对海马神经发生的减少是可逆的，在训练前将动物预先暴露在水迷宫中，这表明与训练相关的压力可能导致了成年神经发生的急性下调。我们认为，在小鼠中，Morris水迷宫不能提供足够纯粹的学习刺激来研究“学习”对成人神经发生的假定影响。此外，我们的数据表明，与啮齿动物的许多认知任务复杂相关的身体活动可能在解释学习对海马细胞可塑性的影响方面发挥重要作用。
Studies in rats that assessed the relation of hippocampus-dependent learning and adult hippocampal neurogenesis suggested a direct regulatory effect of learning on neurogenesis, whereas a similar study in mice had not found such causal link. We here report a substantial decrease of BrdU-positive cells and other measures of adult hippocampal neurogenesis in mice trained in the hidden (HID) or cued version (VIS) of the Morris water maze as compared to untrained animals (CTR). Particularly, cells on advanced stages of neuronal development contributed to this decrease, whereas earlier progenitors (type 2 cells) were not diminished in HID, but were diminished in VIS as compared to CTR. The differential regulation of type 2 cells in HID and VIS may have been caused by a different degree of physical activity, given that a time-yoked control group did not differ from HID, and type 2 cells reportedly constitute the proliferative dentate gyrus population that primarily responds to physical activity. The decrease of hippocampal neurogenesis by water maze training was reversible by pre-exposing animals to the water maze prior to training, suggesting that stress associated with training may have caused the acute downregulation of adult neurogenesis. We propose that in mice the Morris water maze does not provide a pure enough learning stimulus to study the presumed effects of 'learning' on adult neurogenesis. In addition, however, our data show that physical activity that is intricately linked to many cognitive tasks in rodents might play an important role in explaining effects of learning on cellular hippocampal plasticity.