Optogenetic stimulation of a hippocampal engram activates fear memory recall
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Tonegawa_Optogenetic stimulation.pdf
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Author(s)
Liu, Xu
Pang, Petti
Puryear, Corey
Govindarajan, Arvind
Deisseroth, Karl
Tonegawa, Susumu
Ramirez Moreno, Steve
Date Issued
March 2012
Journal
Nature
Publisher
Nature Publishing Group
Citation
Liu, Xu et al. “Optogenetic Stimulation of a Hippocampal Engram Activates Fear Memory Recall.” Nature (2012).
Version
Author's final manuscript
Abstract
A specific memory is thought to be encoded by a sparse population of neurons. These neurons can be tagged during learning for subsequent identification3 and manipulation. Moreover, their ablation or inactivation results in reduced memory expression, suggesting their necessity in mnemonic processes. However, the question of sufficiency remains: it is unclear whether it is possible to elicit the behavioural output of a specific memory by directly activating a population of neurons that was active during learning. Here we show in mice that optogenetic reactivation of hippocampal neurons activated during fear conditioning is sufficient to induce freezing behaviour. We labelled a population of hippocampal dentate gyrus neurons activated during fear learning with channelrhodopsin-2 (ChR2) and later optically reactivated these neurons in a different context. The mice showed increased freezing only upon light stimulation, indicating light-induced fear memory recall. This freezing was not detected in non-fear-conditioned mice expressing ChR2 in a similar proportion of cells, nor in fear-conditioned mice with cells labelled by enhanced yellow fluorescent protein instead of ChR2. Finally, activation of cells labelled in a context not associated with fear did not evoke freezing in mice that were previously fear conditioned in a different context, suggesting that light-induced fear memory recall is context specific. Together, our findings indicate that activating a sparse but specific ensemble of hippocampal neurons that contribute to a memory engram is sufficient for the recall of that memory. Moreover, our experimental approach offers a general method of mapping cellular populations bearing memory engrams.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Picower Institute for Learning and Memory
RIKEN-MIT Center for Neural Circuit Genetics
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1038/nature11028
