美国加州大学Jun-Hyeong Cho团队近期取得重要工作进展，他们研究发现了用于远程语境记忆的新皮层突触印记。相关研究成果2022年12月23日在线发表于《自然—神经科学》杂志上。

据介绍，虽然背景记忆的最初编码涉及海马回路的强化，但这些记忆在新皮质中逐渐成熟为稳定的形式，并减少对海马的依赖。尽管有人提出，语境记忆的长期储存可能涉及新皮质回路中持久的突触变化，但远程语境记忆的突触底物一直是难以捉摸的。

研究人员发现，小鼠远程情境恐惧记忆的巩固与前额叶皮层（PFC）植入神经元之间的兴奋性联系的逐步加强相关，前额叶皮层神经元在学习过程中活跃，在远程记忆回忆过程中重新激活，而远程记忆的消失削弱了这些突触。这种突触特异的可塑性依赖于CREB，需要持续的海马信号，后枕部皮层可以将其传递给PFC。

此外，PFC印迹神经元与远程记忆回忆期间招募的其他PFC神经元紧密相连。这一研究表明，PFC电路的渐进性和突触特异性增强有助于语境记忆的长期存储。

附：英文原文

Title: Neocortical synaptic engrams for remote contextual memories

Author: Lee, Ji-Hye, Kim, Woong Bin, Park, Eui Ho, Cho, Jun-Hyeong

Issue&Volume: 2022-12-23

Abstract: While initial encoding of contextual memories involves the strengthening of hippocampal circuits, these memories progressively mature to stabilized forms in neocortex and become less hippocampus dependent. Although it has been proposed that long-term storage of contextual memories may involve enduring synaptic changes in neocortical circuits, synaptic substrates of remote contextual memories have been elusive. Here we demonstrate that the consolidation of remote contextual fear memories in mice correlated with progressive strengthening of excitatory connections between prefrontal cortical (PFC) engram neurons active during learning and reactivated during remote memory recall, whereas the extinction of remote memories weakened those synapses. This synapse-specific plasticity was CREB-dependent and required sustained hippocampal signals, which the retrosplenial cortex could convey to PFC. Moreover, PFC engram neurons were strongly connected to other PFC neurons recruited during remote memory recall. Our study suggests that progressive and synapse-specific strengthening of PFC circuits can contribute to long-term storage of contextual memories.

DOI: 10.1038/s41593-022-01223-1

Source: https://www.nature.com/articles/s41593-022-01223-1