The dentate gyrus is one of the only brain regions that continues its development after birth in rodents. Adolescence is a very sensitive period during which cognitive competences are programmed. We investigated the role of dentate granule neurons (DGNs) born during adolescence in spatial memory and compared them with those generated earlier in life (in embryos or neonates) or during adulthood by combining functional imaging, retroviral and optogenetic tools to tag and silence DGNs. By imaging DGNs expressing Zif268, a proxy for neuronal activity, we found that neurons generated in adolescent rats (and not embryos or neonates) are transiently involved in spatial memory processing. In contrast, adult-generated DGNs are recruited at a later time point when animals are older. A causal relationship between the temporal origin of DGNs and spatial memory was confirmed by silencing DGNs in behaving animals. Our results demonstrate that the emergence of spatial memory depends on neurons born during adolescence, a function later assumed by neurons generated during adulthood.

齿状回是啮齿动物出生后唯一继续发育的大脑区域之一。青春期是认知能力被编程的一个非常敏感的时期。我们研究了青春期出生的齿状颗粒神经元 (DGN) 在空间记忆中的作用，并通过结合功能成像、逆转录病毒和光遗传学工具来标记和沉默 DGN，将它们与生命早期（胚胎或新生儿）或成年期产生的神经元进行比较。通过对表达 Zif268（神经元活动的代表）的 DGN 进行成像，我们发现青春期大鼠（而不是胚胎或新生儿）中产生的神经元短暂地参与了空间记忆处理。相比之下，成人生成的 DGN 是在动物年龄较大的较晚时间点招募的。DGNs 的时间起源和空间记忆之间的因果关系通过在行为动物中沉默 DGNs 得到证实。我们的研究结果表明，空间记忆的出现取决于青春期出生的神经元，这一功能后来由成年期产生的神经元承担。