Program in Neurosciences & Mental Health, Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada; Department of Physiology, University of Toronto, Toronto, ON M5G 1X8, Canada.
Program in Neurosciences & Mental Health, Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada.
Curr Biol. 2018 Jul 23;28(14):2283-2290.e3. doi: 10.1016/j.cub.2018.05.059. Epub 2018 Jul 5.
Hippocampus-dependent, event-related memories formed in early infancy in human and non-human animals are rapidly forgotten. Recently we found that high levels of hippocampal neurogenesis contribute to accelerated rates of forgetting during infancy. Here, we ask whether these memories formed in infancy are permanently erased (i.e., storage failure) or become progressively inaccessible with time (i.e., retrieval failure). To do this, we developed an optogenetic strategy that allowed us to permanently express channelrhodopsin-2 (ChR2) in neuronal ensembles that were activated during contextual fear encoding in infant mice. We then asked whether reactivation of ChR2-tagged ensembles in the dentate gyrus was sufficient for memory recovery in adulthood. We found that optogenetic stimulation of tagged dentate gyrus neurons recovered "lost" infant memories up to 3 months following training and that memory recovery was associated with broader reactivation of tagged hippocampal and cortical neuronal ensembles.
在人类和非人类动物中,早期婴儿期形成的海马体依赖的、与事件相关的记忆会迅速遗忘。最近,我们发现高水平的海马体神经发生有助于在婴儿期加速遗忘的速度。在这里,我们想知道这些在婴儿期形成的记忆是被永久抹去(即存储失败),还是随着时间的推移逐渐无法访问(即检索失败)。为此,我们开发了一种光遗传学策略,使我们能够在幼年小鼠的情景恐惧编码过程中激活神经元集合,永久性地表达通道视紫红质-2(ChR2)。然后,我们询问在齿状回中重新激活 ChR2 标记的神经元集合是否足以在成年后恢复记忆。我们发现,光遗传学刺激标记的齿状回神经元可以恢复“丢失”的婴儿期记忆,时间长达训练后 3 个月,并且记忆恢复与标记的海马体和皮质神经元集合的更广泛的重新激活有关。