Abstract
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.
| Original language | English (US) |
|---|---|
| Article number | e2117076119 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 119 |
| Issue number | 27 |
| DOIs | |
| State | Published - Jul 5 2022 |
| Externally published | Yes |
Bibliographical note
Funding Information:ACKNOWLEDGMENTS. We thank D. A. Dombeck for sharing the hippocampal window surgery technique; B. K. Kaang and H. Kim for their advice on behavioral experiments and helpful discussions; I. Lee and E.-H. Park for sharing their expertise in VR experiments; and S. Kim and M. Kim for mouse colony management and assistance with image analysis. This research was supported by the Samsung Science and Technology Foundation under Project No. SSTF-BA1602-11. The VR equipment was acquired with funding from a Howard Hughes Medical Institute–Wellcome International Research Scholar Award from the Wellcome Trust [208468/Z/17/Z]. For the purpose of Open Access, the author has applied a CC BY public copyright license to any Author Accepted Manuscript (AAM) version arising from this submission.
Publisher Copyright:
Copyright © 2022 the Author(s).
Keywords
- Arc mRNA
- engram
- in vivo imaging
- memory trace
- virtual reality