Posttraining Ablation of Adult-Generated Neurons Degrades Previously Acquired Memories
Posttraining Ablation of Adult-Generated Neurons Degrades Previously Acquired Memories
复制标题
DOI：
10.1523/jneurosci.3432-11.2011
复制
发表时间：
2011-10-19
影响因子：
5.3
通讯作者：
Frankland, Paul W.
中科院分区：
文献类型：
--
作者：
Arruda-Carvalho, Maithe;Sakaguchi, Masanori;Frankland, Paul W.
新的神经元在成年海马的颗粒下区不断产生，一旦足够成熟，就被认为会整合到海马的记忆回路中。然而，它们是否在随后的记忆表达中发挥重要作用尚不清楚。先前的研究表明，抑制成年神经发生通常（但不总是）会损害随后的海马依赖性学习（即，产生顺行效应）。这些研究的一个主要挑战是，这些新的神经元只代表所有齿状颗粒细胞的一小部分亚群，因此在发育过程中早期产生的颗粒细胞有很大的潜力进行部分或完全补偿。研究这个问题的一个潜在的更强大的方法是在成年人产生的神经元已经成为记忆痕迹的一部分之后消融它们（即，逆行效应）。在这里，我们在小鼠中开发了一种基于白喉毒素的策略，使我们能够在学习之前或之后选择性地消融一群主要成熟的成人产生的神经元，而不影响正在进行的神经发生。在学习之前移除这些神经元并不能阻止新的情境恐惧或水迷宫记忆的形成。相比之下，在学习后去除同等数量的人会降低现有的背景恐惧和水迷宫记忆，而不会影响非海马记忆。即使在学习1个月后，这些成人产生的神经元的消融也会在水迷宫中产生等同的记忆退化。这些逆行效应表明，成人产生的神经元形成海马记忆痕迹的关键和持久的组成部分。
New neurons are continuously generated in the subgranular zone of the adult hippocampus and, once sufficiently mature, are thought to integrate into hippocampal memory circuits. However, whether they play an essential role in subsequent memory expression is not known. Previous studies have shown that suppression of adult neurogenesis often (but not always) impairs subsequent hippocampus-dependent learning (i.e., produces anterograde effects). A major challenge for these studies is that these new neurons represent only a small subpopulation of all dentate granule cells, and so there is large potential for either partial or complete compensation by granule cells generated earlier on during development. A potentially more powerful approach to investigate this question would be to ablate adult-generated neurons after they have already become part of a memory trace (i.e., retrograde effects). Here we developed a diphtheria toxin-based strategy in mice that allowed us to selectively ablate a population of predominantly mature, adult-generated neurons either before or after learning, without affecting ongoing neurogenesis. Removal of these neurons before learning did not prevent the formation of new contextual fear or water maze memories. In contrast, removal of an equivalent population after learning degraded existing contextual fear and water maze memories, without affecting nonhippocampal memory. Ablation of these adult-generated neurons even 1 month after learning produced equivalent memory degradation in the water maze. These retrograde effects suggest that adult-generated neurons form a critical and enduring component of hippocampal memory traces.