Increasing neurogenesis refines hippocampal activity rejuvenating navigational learning strategies and contextual memory throughout life
Increasing neurogenesis refines hippocampal activity rejuvenating navigational learning strategies and contextual memory throughout life
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DOI：
10.1038/s41467-019-14026-z
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发表时间：
2020-01-09
影响因子：
16.6
通讯作者：
Calegari, Federico
中科院分区：
文献类型：
--
作者：
Berdugo-Vega, Gabriel;Arias-Gil, Gonzalo;Calegari, Federico
随着年龄的增长，大脑的功能可塑性下降，导致背景学习、以他为中心的导航和情景记忆的明显缺陷。成年神经发生是海马可塑性促进信息情境化的一个主要例子，并且在衰老过程中急剧减少。我们发现，通过过度表达细胞周期调节因子Cdk 4/cyclinD 1的遗传驱动的神经干细胞扩增补偿了神经发生中与年龄相关的下降。这引发了对三突触海马回路的整体抑制作用，导致已知为记忆巩固基础的CA 1尖波波纹的变化。最重要的是，增加神经发生挽救了年龄相关的开关，从海马到纹状体的学习策略，拯救allocentric导航和上下文记忆。我们的研究表明，海马体功能的关键方面可以在老年时逆转，或者通过利用大脑的内源性神经干细胞储备在一生中得到补偿。
Functional plasticity of the brain decreases during ageing causing marked deficits in contextual learning, allocentric navigation and episodic memory. Adult neurogenesis is a prime example of hippocampal plasticity promoting the contextualisation of information and dramatically decreases during ageing. We found that a genetically-driven expansion of neural stem cells by overexpression of the cell cycle regulators Cdk4/cyclinD1 compensated the age-related decline in neurogenesis. This triggered an overall inhibitory effect on the trisynaptic hippocampal circuit resulting in a changed profile of CA1 sharp-wave ripples known to underlie memory consolidation. Most importantly, increased neurogenesis rescued the age-related switch from hippocampal to striatal learning strategies by rescuing allocentric navigation and contextual memory. Our study demonstrates that critical aspects of hippocampal function can be reversed in old age, or compensated throughout life, by exploiting the brain's endogenous reserve of neural stem cells.