A developmental brain-wide screen identifies retrosplenial cortex as a key player in the emergence of persistent memory.
A developmental brain-wide screen identifies retrosplenial cortex as a key player in the emergence of persistent memory.
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全脑发育筛选将压后皮层识别为持久记忆出现的关键参与者。
DOI：
10.1101/2024.01.07.574554
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
DeNardo,LauraA
中科院分区：
文献类型：
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作者：
Jin,Benita;Gongwer,MichaelW;Ohanian,Lilit;Holden-Wingate,Lucinda;Le,Bryan;Darmawan,Alfonso;Nakayama,Yuka;RuedaMora,SophiaA;DeNardo,LauraA
生命早期形成的记忆是短暂的，而那些后来形成的记忆则会持续下去。最近的研究表明，婴儿的记忆是以潜伏状态储存的。但是为什么它们不能被检索到却知之甚少。在这里，我们研究了婴儿健忘症背后的全脑回路机制。我们进行了一个屏幕，结合上下文的恐惧条件反射，活动依赖性神经元标记在不同的出生后年龄，组织清除和光片显微镜。我们观察到婴儿，青少年和成年小鼠之间的区域活动模式显着的发展变化，包括在压后皮质（RSP）的变化，与持久性记忆的出现。然后，我们进行了一系列有针对性的调查RSP的结构和功能的发展。在学习后的一周内，标记的RSP集合的慢性化学发生再激活增强了成人和青少年的记忆力，但在婴儿中没有。然而，33天后，重新激活婴儿标记的RSP合奏恢复了遗忘的记忆。伴随着树突棘密度的变化，这些合奏可以重新激活上下文线索的可能性，RSP记忆合奏的发展功能的变化。这些研究表明，RSP集合存储潜在的婴儿记忆，揭示了RSP功能成熟的时间过程，并建议不成熟的RSP功能网络有助于婴儿健忘症。
Memories formed early in life are short-lived while those formed later persist. Recent work revealed that infant memories are stored in a latent state. But why they fail to be retrieved is poorly understood. Here we investigated brain-wide circuit mechanisms underlying infantile amnesia. We performed a screen that combined contextual fear conditioning, activity-dependent neuronal tagging at different postnatal ages, tissue clearing and light sheet microscopy. We observed striking developmental changes in regional activity patterns between infant, juvenile, and adult mice, including changes in the retrosplenial cortex (RSP) that aligned with the emergence of persistent memory. We then performed a series of targeted investigations of RSP structure and function across development. Chronic chemogenetic reactivation of tagged RSP ensembles during the week after learning enhanced memory in adults and juveniles, but not in infants. However, after 33 days, reactivating infant-tagged RSP ensembles recovered forgotten memories. Changes in the developmental functions of RSP memory ensembles were accompanied by changes in dendritic spine density and the likelihood that those ensembles could be reactivated by contextual cues. These studies show that RSP ensembles store latent infant memories, reveal the time course of RSP functional maturation, and suggest that immature RSP functional networks contribute to infantile amnesia.