Levels of adult neurogenesis in the dentate gyrus (DG) of the hippocampus are correlated with unique cognitive functions. However, the molecular pathways controlling it are poorly understood. Here, we found that the known physiological ways to enhance neurogenesis converged on the eEF2/eEF2K pathway via AMPK in the DG. Enhancing the elongation phase of mRNA translation in eEF2K-knockout (eEF2K-KO) mice induced the expression of neurogenesis-related proteins in the hippocampus. We thus tested the hypothesis that inducing eEF2K-KO in mature neurons of the DG controls neurogenesis. Indeed, both general eEF2K-KO and targeted KO in DG excitatory mature neurons resulted in enhanced neurogenesis levels and upregulation of neurogenesis-related proteins. Increased neurogenesis was correlated with enhanced performance in DG-dependent learning. Moreover, general and local eEF2K-KO in old mice rejuvenated the DG, paving the way for better mechanistic understanding of how neurogenesis is controlled in the mature DG and possible treatments for incurable aging-associated diseases.

海马齿状回 (DG) 中成体神经发生的水平与独特的认知功能相关。然而，控制它的分子途径知之甚少。在这里，我们发现已知的促进神经发生的生理方式通过 DG 中的 AMPK 集中在 eEF2/eEF2K 通路上。在 eEF2K 基因敲除 (eEF2K-KO) 小鼠中，增强 mRNA 翻译的延伸阶段可诱导海马中神经发生相关蛋白的表达。因此，我们测试了在 DG 的成熟神经元中诱导 eEF2K-KO 控制神经发生的假设。事实上，DG 兴奋性成熟神经元中的一般 eEF2K-KO 和靶向 KO 均导致神经发生水平增强和神经发生相关蛋白的上调。神经发生的增加与 DG 依赖性学习的表现增强相关。而且，