Department of Psychology, Wilfrid Laurier University, 75 University Ave W, Waterloo, ON N2L 3C5, Canada.
BMC Neurosci. 2013 Sep 13;14:100. doi: 10.1186/1471-2202-14-100.
Aging is typically accompanied by memory decline and changes in hippocampal function. Among these changes is a decline in the activity of the dentate gyrus (DG) during behavior. Lasting memory, however, is thought to also require recapitulation of recent memory traces during subsequent rest - a phenomenon, termed memory trace reactivation, which is compromised in hippocampal CA1 with progressive age. This process has yet to be assessed in the aged DG, despite its prominent role in age-related memory impairment. Using zif268 transcription to measure granule cell recruitment, DG activity in adult and aged animals was assessed both during spatial exploration and as animals remained at rest in the home cage in order to detect potential memory-related replay.
Consistent with the observation of memory trace reactivation in DG, the probability that an individual granule cell transcribes zif268 during rest in the animal's home cage is increased by recent experience in a novel environment. Surprisingly, a comparable increase was observed in the probability of granule cells in the aged DG expressing zif268 during rest. Moreover, no significant age-related difference was observed in the number of granule cells expressing zif268 during rest. Thus, the number and pattern of granule cell expression of zif268 during rest is preserved in aged animals, despite a significant decline in exploration-related zif268 expression.
These data lead to the hypothesis that the input the aged DG receives from backprojections from CA3 (the region widely hypothesized to mediate reactivation) remains functionally intact despite loss of innervation from the perforant path.
衰老通常伴随着记忆衰退和海马功能变化。这些变化之一是在行为过程中,齿状回(DG)的活动减少。然而,人们认为持久的记忆还需要在随后的休息期间重新激活最近的记忆痕迹——这一现象被称为记忆痕迹再激活,随着年龄的增长,海马 CA1 中的这种现象会受到损害。尽管 DG 在与年龄相关的记忆障碍中起着重要作用,但在衰老的 DG 中尚未评估这一过程。本研究使用 zif268 转录来衡量颗粒细胞的募集情况,评估成年和老年动物在空间探索过程中的 DG 活性,以及动物在其巢穴中静止时的 DG 活性,以检测潜在的与记忆相关的重放。
与 DG 中记忆痕迹再激活的观察结果一致,在动物的巢穴中休息时,单个颗粒细胞转录 zif268 的概率会因在新环境中的近期经历而增加。令人惊讶的是,在衰老的 DG 中,颗粒细胞在休息时表达 zif268 的概率也观察到了类似的增加。此外,在休息时表达 zif268 的颗粒细胞数量在年龄相关方面没有显著差异。因此,尽管与探索相关的 zif268 表达显著下降,但在老年动物中,休息时颗粒细胞表达 zif268 的数量和模式仍然得以保留。
这些数据导致了一个假设,即衰老的 DG 从 CA3 (广泛假设为介导再激活的区域)接收的输入仍然保持功能完整,尽管从穿通路径失去了神经支配。