期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：27
DOI：10.1073/pnas.2117076119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
Arc is one of the genes that are rapidly transcribed by neuronal activity and thus used as a marker for memory trace or engram cells. However, the dynamics of engram cell populations is not well-known because of the difficulty in monitoring the rapid and transient gene expression in live animals. Using a mouse model in which endogenous
Arc messenger RNA (mRNA) is fluorescently labeled, we demonstrate that
Arc-expressing neuronal populations have distinct dynamics in different brain regions and that only a small subpopulation that consistently expresses
Arc during both memory encoding and retrieval exhibits context-specific calcium activity. This live-animal RNA-imaging technique will offer a powerful tool for connecting gene expression to neuronal activity patterns and to behavior.
Memories are thought to be encoded in populations of neurons called memory trace or engram cells. However, little is known about the dynamics of these cells because of the difficulty in real-time monitoring of them over long periods of time in vivo. To overcome this limitation, we present a genetically encoded RNA indicator (GERI) mouse for intravital chronic imaging of endogenous
Arc messenger RNA (mRNA)—a popular marker for memory trace cells. We used our GERI to identify
Arc-positive neurons in real time without the delay associated with reporter protein expression in conventional approaches. We found that the
Arc-positive neuronal populations rapidly turned over within 2 d in the hippocampal CA1 region, whereas ∼4% of neurons in the retrosplenial cortex consistently expressed
Arc following contextual fear conditioning and repeated memory retrievals. Dual imaging of GERI and a calcium indicator in CA1 of mice navigating a virtual reality environment revealed that only the population of neurons expressing
Arc during both encoding and retrieval exhibited relatively high calcium activity in a context-specific manner. This in vivo RNA-imaging approach opens the possibility of unraveling the dynamics of the neuronal population underlying various learning and memory processes.
关键词：enArcmRNAin vivo imagingvirtual realitymemory traceengram
