Primary Cilia Regulate Proliferation of Amplifying Progenitors in Adult Hippocampus: Implications for Learning and Memory
Primary Cilia Regulate Proliferation of Amplifying Progenitors in Adult Hippocampus: Implications for Learning and Memory
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DOI：
10.1523/jneurosci.1062-11.2011
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发表时间：
2011-07-06
影响因子：
5.3
通讯作者：
Terskikh, Alexey V.
中科院分区：
文献类型：
--
作者：
Amador-Arjona, Alejandro;Elliott, Jimmy;Terskikh, Alexey V.
将新神经元整合到成年海马区与特定类型的学习有关。在发育过程中，海马齿状回中的成体神经干细胞(NSCs)的形成需要初级纤毛。然而，对纤毛在成年神经干细胞维持中的需求尚不清楚。我们建立了一种遗传性小鼠模型，在该模型中，胎儿/围产期的脑发育不受影响，但通过有条件地切除成人GFAP(+)神经干细胞/祖细胞中的初级纤毛，成人海马区的神经发生持续减少。我们发现，这种方法特别地减少了海马体扩增前体细胞(也称为2a型细胞)的数量，而不影响放射状神经干细胞(或1型细胞)的数量。成年海马区神经发生的持续减少会导致空间学习的延迟，而不是永久性的缺陷，而不会影响长期记忆的保持。神经发生的减少也改变了空间新颖性识别和海马体独立线索条件反射。在这里，我们认为成年的海马区新生神经元提高了产生新的空间记忆表征的效率，成年海马区神经发生的减少可能倾向于基于线索的策略。这一新的小鼠模型提供了与纤毛缺陷(纤毛疾病)相关的认知缺陷的证据，部分原因可能是成人海马干/祖细胞初级纤毛的缺陷。
Integration of new neurons into the adult hippocampus has been linked to specific types of learning. Primary cilia were found to be required for the formation of adult neural stem cells (NSCs) in the hippocampal dentate gyrus during development. However, the requirement of cilia in maintenance of adult NSCs is unknown. We developed a genetic mouse model in which fetal/perinatal brain development is unaffected, but adult hippocampal neurogenesis is constantly reduced by conditional ablation of primary cilia in adult GFAP(+) neural stem/progenitor cells. We found that this approach specifically reduces the number of hippocampal amplifying progenitors (also called type 2a cells) without affecting the number of radial NSCs (or type 1 cells). Constant reduction of adult hippocampal neurogenesis produced a delay rather than a permanent deficiency in spatial learning without affecting the retention of long-term memories. Decreased neurogenesis also altered spatial novelty recognition and hippocampus-independent cue conditioning. Here, we propose that adult hippocampal newborn neurons increase the efficiency of generating the new representations of spatial memories and that reduction of adult hippocampal neurogenesis may be biased toward cue-based strategies. This novel mouse model provides evidences that cognitive deficits associated with ciliary defects (ciliopathies) might be, in part, mediated by the deficiency of primary cilia in adult hippocampal stem/progenitor cells.