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dc.contributor.authorLiu, Xu
dc.contributor.authorRamirez, Steve
dc.contributor.authorPang, Petti
dc.contributor.authorPuryear, Corey
dc.contributor.authorGovindarajan, Arvind
dc.contributor.authorDeisseroth, Karl
dc.contributor.authorTonegawa, Susumu
dc.date.accessioned2012-11-15T18:26:52Z
dc.date.available2012-11-15T18:26:52Z
dc.date.issued2012-03
dc.date.submitted2011-11
dc.identifier.urihttp://hdl.handle.net/1721.1/74651
dc.description.abstractA 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.en_US
dc.description.sponsorshipRIKEN Brain Science Instituteen_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant R01-MH078821)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant P50-MH58880)en_US
dc.language.isoen_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionofhttp://dx.doi.org/10.1038/nature11028en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.rights.urien_US
dc.sourcePMCen_US
dc.titleOptogenetic stimulation of a hippocampal engram activates fear memory recallen_US
dc.typeArticleen_US
dc.identifier.citationLiu, Xu et al. “Optogenetic Stimulation of a Hippocampal Engram Activates Fear Memory Recall.” Nature (2012).en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Brain and Cognitive Sciencesen_US
dc.contributor.departmentPicower Institute for Learning and Memoryen_US
dc.contributor.departmentRIKEN-MIT Center for Neural Circuit Geneticsen_US
dc.contributor.mitauthorLiu, Xu
dc.contributor.mitauthorRamirez, Steve
dc.contributor.mitauthorPang, Petti
dc.contributor.mitauthorPuryear, Corey
dc.contributor.mitauthorGovindarajan, Arvind
dc.contributor.mitauthorTonegawa, Susumu
dc.relation.journalNatureen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsLiu, Xu; Ramirez, Steve; Pang, Petti T.; Puryear, Corey B.; Govindarajan, Arvind; Deisseroth, Karl; Tonegawa, Susumuen
dc.identifier.orcidhttps://orcid.org/0000-0003-2839-8228
dc.identifier.orcidhttps://orcid.org/0000-0002-6697-8330
dc.identifier.orcidhttps://orcid.org/0000-0003-3984-6057
mit.licensePUBLISHER_POLICYen_US


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