Examining memory linking and generalization using scFLARE2, a temporally precise neuronal activity tagging system.
Examining memory linking and generalization using scFLARE2, a temporally precise neuronal activity tagging system.
复制标题
使用 scFLARE2（一种时间精确的神经元活动标记系统）检查记忆链接和泛化。
DOI：
10.1016/j.celrep.2023.113592
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发表时间：
2023
期刊：
影响因子：
8.8
通讯作者：
Josselyn,SheenaA
中科院分区：
文献类型：
--
作者：
Jung,JungHoon;Wang,Ying;Rashid,AsimJ;Zhang,Tao;Frankland,PaulW;Josselyn,SheenaA
记忆在大脑中的组织方式影响着它们是被离散地记住，还是与其他经历联系在一起，或者是广义信息是否被应用于完全陌生的情况。在这里，我们使用scFLARE2（单链快速光和活动调节表达2），一种时间精确的标记系统，来操纵小鼠侧杏仁核神经元在两次3分钟威胁经历中的一次活动，这些威胁经历发生在时间上接近（3小时）或更远（27小时）。沉默scflare2标记的神经元表明，发生在远端时间的两个威胁经历被分配到正交的印痕组合中并被分散记忆，而发生在近时间上的相同的两个威胁经历通过共同分配与重叠的印痕组合联系在一起。此外，我们发现，共同分配介导记忆泛化应用于一个完全新的刺激。这些结果表明，印迹集合神经元兴奋性的内源性时间进化决定了记忆的组织和记忆方式，而传统的基于即时早期基因的标记方法无法做到这一点。
How memories are organized in the brain influences whether they are remembered discretely versus linked with other experiences or whether generalized information is applied to entirely novel situations. Here, we used scFLARE2 (single-chain fast light- and activity-regulated expression 2), a temporally precise tagging system, to manipulate mouse lateral amygdala neurons active during one of two 3 min threat experiences occurring close (3 h) or further apart (27 h) in time. Silencing scFLARE2-tagged neurons showed that two threat experiences occurring at distal times are dis-allocated to orthogonal engram ensembles and remembered discretely, whereas the same two threat experiences occurring in close temporal proximity are linked via co-allocation to overlapping engram ensembles. Moreover, we found that co-allocation mediates memory generalization applied to a completely novel stimulus. These results indicate that endogenous temporal evolution of engram ensemble neuronal excitability determines how memories are organized and remembered and that this would not be possible using conventional immediate-early gene-based tagging methods.