한빛사논문
Byung Hun Leea,1, Jae Youn Shima,1, Hyungseok C. Moona, Dong Wook Kima, Jiwon Kimb, Jang Soo Yookb, Jinhyun Kimb, and Hye Yoon Parka,c,d,2
aDepartment of Physics and Astronomy, Seoul National University,Seoul 08826, Korea;
bCenter for Functional Connectomics, Brain Science Institute,Korea Institute of Science and Technology, Seoul 02792, Korea;
cThe Institute of Applied Physics, Seoul National University, Seoul 08826, Korea;
and dDepartment of Electrical and Computer Engineering, University of Minnesota, Minneapolis, MN 55455
1B.H.L. and J.Y.S. contributed equally to this work.
2To whom correspondence may be addressed : Hye Yoon Park
Abstract
Memories are thought to be encoded in populations of neurons called memory trace orengram cells. However, little is known about the dynamics of these cells because of thedifficulty in real-time monitoring of them over long periods of time in vivo. To over-come this limitation, we present a genetically encoded RNA indicator (GERI) mousefor intravital chronic imaging of endogenousArcmessenger RNA (mRNA)—a popularmarker for memory trace cells. We used our GERI to identifyArc-positive neurons inreal time without the delay associated with reporter protein expression in conventionalapproaches. We found that theArc-positive neuronal populations rapidly turned overwithin 2 d in the hippocampal CA1 region, whereas∼4% of neurons in the retrosple-nial cortex consistently expressedArcfollowing contextual fear conditioning andrepeated memory retrievals. Dual imaging of GERI and a calcium indicator in CA1 ofmice navigating a virtual reality environment revealed that only the population of neu-rons expressingArcduring both encoding and retrieval exhibited relatively high calciumactivity in a context-specific manner. This in vivo RNA-imaging approach opens thepossibility of unraveling the dynamics of the neuronal population underlying variouslearning and memory processes.
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