title: Optogenetic stimulation of a hippocampal engram activates fear memory recall.
abstract: A specific memory is thought to be encoded by a sparse population of neurons. These neurons can be tagged during learning for subsequent                     identification 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.
authors.affiliation: RIKEN-MIT Center for Neural Circuit Genetics at the Picower Institute for Learning and Memory, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Liu
authors.forename: Steve
authors.initials: S
authors.lastname: Ramirez
authors.forename: Petti T
authors.initials: PT
authors.lastname: Pang
authors.forename: Corey B
authors.initials: CB
authors.lastname: Puryear
authors.forename: Arvind
authors.initials: A
authors.lastname: Govindarajan
authors.forename: Karl
authors.initials: K
authors.lastname: Deisseroth
authors.forename: Susumu
authors.initials: S
authors.lastname: Tonegawa
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D000075402:Channelrhodopsins; D003213:Conditioning, Psychological / Q000502:physiology / Q000528:radiation effects; D018891:Dentate Gyrus / Q000166:cytology / Q000502:physiology / Q000528:radiation effects; D005239:Fear / Q000502:physiology* / Q000528:radiation effects*; D005260:Female; D046352:Freezing Reaction, Cataleptic / Q000502:physiology / Q000528:radiation effects; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects*; D008027:Light; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D011939:Mental Recall / Q000528:radiation effects*; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D001426:Bacterial Proteins; D000075402:Channelrhodopsins; D008164:Luminescent Proteins; C054562:yellow fluorescent protein, Bacteria