Publication Date:
2012-03-24
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3331914/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3331914/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Xu -- Ramirez, Steve -- Pang, Petti T -- Puryear, Corey B -- Govindarajan, Arvind -- Deisseroth, Karl -- Tonegawa, Susumu -- P50 MH058880/MH/NIMH NIH HHS/ -- P50 MH058880-10/MH/NIMH NIH HHS/ -- P50-MH58880/MH/NIMH NIH HHS/ -- R01 MH078821/MH/NIMH NIH HHS/ -- R01 MH078821-17/MH/NIMH NIH HHS/ -- R01-MH078821/MH/NIMH NIH HHS/ -- England -- Nature. 2012 Mar 22;484(7394):381-5. doi: 10.1038/nature11028.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉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.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22441246" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Bacterial Proteins/genetics/metabolism
;
Conditioning (Psychology)/physiology/radiation effects
;
Dentate Gyrus/cytology/physiology/radiation effects
;
Fear/*physiology/*radiation effects
;
Female
;
Freezing Reaction, Cataleptic/physiology/radiation effects
;
Gene Expression Regulation
;
Hippocampus/cytology/*physiology/*radiation effects
;
Light
;
Luminescent Proteins/genetics/metabolism
;
Male
;
Mental Recall/*radiation effects
;
Mice
;
Mice, Transgenic
;
Rhodopsin/genetics/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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