Adult-generated hippocampal neurons allow the flexible use of spatially precise learning strategies.
Adult-generated hippocampal neurons allow the flexible use of spatially precise learning strategies.
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DOI：
10.1371/journal.pone.0005464
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Kempermann G
中科院分区：
文献类型：
--
作者：
Garthe A;Behr J;Kempermann G
尽管在过去的几年里取得了巨大的进展，但新生颗粒细胞对成年海马功能的具体贡献仍然不清楚。我们假设，为了解决这个问题，必须特别注意学习测试的具体设计，分析和解释。因此，我们设计了一个行为实验，沿着假设来自计算模型预测，新的神经元可能是特别相关的学习条件，其中新的方面出现在熟悉的情况下，从而把高要求的定性方面的（再）学习。在参考记忆版本的水迷宫任务抑制成年神经发生与替莫唑胺（TMZ）引起了高度特异性的学习缺陷。在Morris水迷宫的隐藏平台版本中测试小鼠（每天6次试验，持续5天，在第4天逆转平台位置）。在四个治疗周期结束后4周进行测试，以最大限度地减少测试时潜在可招募的新神经元的数量。神经发生的减少并没有改变CA3和齿状回的长时程增强，但取消了归因于新神经元的齿状回LTP的一部分。TMZ在测试时没有任何明显的副作用，治疗组和对照组都学会了找到隐藏的平台。然而，搜索策略的定性分析表明，治疗小鼠没有提前空间精确的搜索策略，特别是当学习改变目标位置（逆转）。因此，齿状回中的新神经元似乎是必要的，以增加灵活性的一些依赖于海马的定性参数的学习。我们的发现，缺乏成人产生的颗粒细胞，具体导致动物的无法精确定位一个隐藏的目标，也是根据一个专门的作用，齿状回在产生一个度量，而不仅仅是一个配置地图的环境。因此，发现高度特异性的行为缺陷作为抑制成年海马神经发生的结果，允许将细胞海马可塑性与理论模型中定义明确的假设联系起来。
Despite enormous progress in the past few years the specific contribution of newly born granule cells to the function of the adult hippocampus is still not clear. We hypothesized that in order to solve this question particular attention has to be paid to the specific design, the analysis, and the interpretation of the learning test to be used. We thus designed a behavioral experiment along hypotheses derived from a computational model predicting that new neurons might be particularly relevant for learning conditions, in which novel aspects arise in familiar situations, thus putting high demands on the qualitative aspects of (re-)learning. In the reference memory version of the water maze task suppression of adult neurogenesis with temozolomide (TMZ) caused a highly specific learning deficit. Mice were tested in the hidden platform version of the Morris water maze (6 trials per day for 5 days with a reversal of the platform location on day 4). Testing was done at 4 weeks after the end of four cycles of treatment to minimize the number of potentially recruitable new neurons at the time of testing. The reduction of neurogenesis did not alter longterm potentiation in CA3 and the dentate gyrus but abolished the part of dentate gyrus LTP that is attributed to the new neurons. TMZ did not have any overt side effects at the time of testing, and both treated mice and controls learned to find the hidden platform. Qualitative analysis of search strategies, however, revealed that treated mice did not advance to spatially precise search strategies, in particular when learning a changed goal position (reversal). New neurons in the dentate gyrus thus seem to be necessary for adding flexibility to some hippocampus-dependent qualitative parameters of learning. Our finding that a lack of adult-generated granule cells specifically results in the animal's inability to precisely locate a hidden goal is also in accordance with a specialized role of the dentate gyrus in generating a metric rather than just a configurational map of the environment. The discovery of highly specific behavioral deficits as consequence of a suppression of adult hippocampal neurogenesis thus allows to link cellular hippocampal plasticity to well-defined hypotheses from theoretical models.
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影响因子：
9.8
作者：
Dupret D;Fabre A;Döbrössy MD;Panatier A;Rodríguez JJ;Lamarque S;Lemaire V;Oliet SH;Piazza PV;Abrous DN
通讯作者：
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影响因子：
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