Doctoral Program in Chemical and Biological Sciences, The Scripps Research Institute, La Jolla, CA 92037.
Psychiatry Department, University of California, San Diego, La Jolla, CA 92093.
Proc Natl Acad Sci U S A. 2019 Apr 23;116(17):8576-8581. doi: 10.1073/pnas.1818432116. Epub 2019 Mar 15.
The neural circuits underlying memory change over prolonged periods after learning, in a process known as systems consolidation. Postlearning spontaneous reactivation of memory-related neural ensembles is thought to mediate this process, although a causal link has not been established. Here we test this hypothesis in mice by using optogenetics to selectively reactivate neural ensembles representing a contextual fear memory (sometimes referred to as engram neurons). High-frequency stimulation of these ensembles in the retrosplenial cortex 1 day after learning produced a recent memory with features normally observed in consolidated remote memories, including higher engagement of neocortical areas during retrieval, contextual generalization, and decreased hippocampal dependence. Moreover, this effect was only present if memory ensembles were reactivated during sleep or light anesthesia. These results provide direct support for postlearning memory ensemble reactivation as a mechanism of systems consolidation, and show that this process can be accelerated by ensemble reactivation in an unconscious state.
学习后长时间内，记忆相关的神经回路会发生改变，这个过程被称为系统巩固。学习后自发的记忆相关神经集合的再激活被认为介导了这个过程，尽管还没有建立因果关系。在这里，我们通过使用光遗传学在小鼠中测试了这一假说，选择性地再激活代表情景性恐惧记忆的神经集合（有时称为记忆痕迹神经元）。在学习后 1 天，对后扣带回皮层中的这些集合进行高频刺激，产生了具有巩固后远程记忆中通常观察到的特征的近期记忆，包括在检索过程中更多地参与新皮质区域、上下文泛化和减少海马依赖性。此外，如果在睡眠或轻度麻醉期间重新激活记忆集合，则仅出现这种效果。这些结果为学习后记忆集合再激活作为系统巩固的一种机制提供了直接支持，并表明在无意识状态下通过集合再激活可以加速这一过程。
