Princeton Neuroscience Institute and Department of Psychology, Princeton University, Princeton, NJ 08544.
National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892.
eNeuro. 2020 Dec 22;7(6). doi: 10.1523/ENEURO.0182-20.2020. Print 2020 Nov-Dec.
Throughout adulthood, the dentate gyrus continues to produce new granule cells, which integrate into the hippocampal circuitry. New neurons have been linked to several known functions of the hippocampus, including learning and memory, anxiety and stress regulation, and social behavior. We explored whether transgenic reduction of adult-born neurons in mice would impair social memory and the formation of social dominance hierarchies. We used a conditional transgenic mouse strain [thymidine kinase (TK) mice] that selectively reduces adult neurogenesis by treatment with the antiviral drug valganciclovir (VGCV). TK mice treated with VGCV were unable to recognize conspecifics as familiar 24 h after initial exposure. We then explored whether reducing new neurons completely impaired their ability to acquire or retrieve a social memory and found that TK mice treated with VGCV were able to perform at control levels when the time between exposure (acquisition) and reexposure (retrieval) was brief. We next explored whether adult-born neurons are involved in dominance hierarchy formation by analyzing their home cage behavior as well as their performance in the tube test, a social hierarchy test, and did not find any consistent alterations in behavior between control and TK mice treated with VGCV. These data suggest that adult neurogenesis is essential for social memory maintenance, but not for acquisition nor retrieval over a short time frame, with no effect on social dominance hierarchy. Future work is needed to explore whether the influence of new neurons on social memory is mediated through connections with the CA2, an area involved in social recognition.
在整个成年期，齿状回持续产生新的颗粒细胞，这些细胞整合到海马回路中。新神经元与海马体的几个已知功能有关，包括学习和记忆、焦虑和应激调节以及社会行为。我们探讨了减少成年小鼠海马体中新生神经元是否会损害社会记忆和社会优势等级的形成。我们使用了一种条件性转基因小鼠品系（胸苷激酶（TK）小鼠），通过用抗病毒药物缬更昔洛韦（VGCV）处理来选择性地减少成年神经发生。用 VGCV 处理的 TK 小鼠在初次暴露后 24 小时内无法识别同种小鼠。然后，我们探讨了减少新神经元是否完全损害了它们获得或检索社会记忆的能力，发现当暴露（获得）和重新暴露（检索）之间的时间很短时，用 VGCV 处理的 TK 小鼠能够以对照水平进行操作。接下来，我们通过分析它们的笼内行为以及在管测试（一种社会等级测试）中的表现，探讨了成年新生神经元是否参与优势等级的形成，在管测试中，我们没有发现对照和用 VGCV 处理的 TK 小鼠之间的行为有任何一致的变化。这些数据表明，成年神经发生对于维持社会记忆是必不可少的，但在短时间内对于获得和检索来说并非必需，并且对社会优势等级没有影响。未来的工作需要探索新神经元对社会记忆的影响是否通过与 CA2 的连接来介导，CA2 是一个参与社会识别的区域。
