Department of Biology, Stanford University, Stanford, CA, USA.
Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA.
Nat Neurosci. 2019 Mar;22(3):460-469. doi: 10.1038/s41593-018-0318-7. Epub 2019 Jan 28.
Memories of fearful events can last a lifetime. The prelimbic (PL) cortex, a subregion of prefrontal cortex, plays a critical role in fear memory retrieval over time. Most studies have focused on acquisition, consolidation, and retrieval of recent memories, but much less is known about the neural mechanisms of remote memory. Using a new knock-in mouse for activity-dependent genetic labeling (TRAP2), we demonstrate that neuronal ensembles in the PL cortex are dynamic. PL neurons TRAPed during later memory retrievals are more likely to be reactivated and make larger behavioral contributions to remote memory retrieval compared to those TRAPed during learning or early memory retrieval. PL activity during learning is required to initiate this time-dependent reorganization in PL ensembles underlying memory retrieval. Finally, while neurons TRAPed during earlier and later retrievals have similar broad projections throughout the brain, PL neurons TRAPed later have a stronger functional recruitment of cortical targets.
恐惧事件的记忆可以持续一生。前额皮层的前扣带皮层（PL）在随时间提取恐惧记忆方面起着至关重要的作用。大多数研究都集中在最近记忆的获取、巩固和检索上，但对远距离记忆的神经机制知之甚少。使用一种新的用于活性依赖性遗传标记的基因敲入小鼠（TRAP2），我们证明了 PL 皮层中的神经元集合是动态的。与在学习或早期记忆检索期间被 TRAP 的神经元相比，在后期记忆检索过程中被 TRAP 的 PL 神经元更有可能被重新激活，并对远程记忆检索做出更大的行为贡献。学习过程中的 PL 活动是启动记忆检索中这种随时间变化的 PL 集合重组所必需的。最后，虽然在早期和晚期检索过程中被 TRAP 的神经元在整个大脑中具有相似的广泛投射，但在晚期被 TRAP 的 PL 神经元具有更强的皮质目标功能募集。
