Inception of a false memory by optogenetic manipulation of a hippocampal memory engram

Memories can be easily distorted, and a lack of relevant animal models has largely hindered our understanding of false-memory formation. Here, we first identified a population of cells in the dentate gyrus (DG) of the hippocampus that bear the engrams for a specific context; these cells were natural...

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Main Authors: Liu, Xu, Ramirez Moreno, Steve, Tonegawa, Susumu
Other Authors: Massachusetts Institute of Technology. Department of Biology
Format: Article
Language:en_US
Published: Royal Society 2015
Online Access:http://hdl.handle.net/1721.1/98083
https://orcid.org/0000-0003-2839-8228
https://orcid.org/0000-0002-6697-8330
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author Liu, Xu
Ramirez Moreno, Steve
Tonegawa, Susumu
author2 Massachusetts Institute of Technology. Department of Biology
author_facet Massachusetts Institute of Technology. Department of Biology
Liu, Xu
Ramirez Moreno, Steve
Tonegawa, Susumu
author_sort Liu, Xu
collection MIT
description Memories can be easily distorted, and a lack of relevant animal models has largely hindered our understanding of false-memory formation. Here, we first identified a population of cells in the dentate gyrus (DG) of the hippocampus that bear the engrams for a specific context; these cells were naturally activated during the encoding phase of fear conditioning and their artificial reactivation using optogenetics in an unrelated context was sufficient for inducing the fear memory specific to the conditioned context. In a further study, DG or CA1 neurons activated by exposure to a particular context were labelled with channelrhodopsin-2 (ChR2). These neurons were later optically reactivated during fear conditioning in a different context. The DG experimental group showed increased freezing in the original context in which a foot shock was never delivered. The recall of this false memory was context specific, activated similar downstream regions engaged during natural fear-memory recall, and was also capable of driving an active fear response. Together, our data demonstrate that by substituting a natural conditioned stimulus with optogenetically reactivated DG cells that bear contextual memory engrams, it is possible to incept an internally and behaviourally represented false fear memory.
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spelling mit-1721.1/980832022-10-02T00:17:09Z Inception of a false memory by optogenetic manipulation of a hippocampal memory engram Liu, Xu Ramirez Moreno, Steve Tonegawa, Susumu 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 Tonegawa, Susumu Liu, Xu Ramirez Moreno, Steve Tonegawa, Susumu Memories can be easily distorted, and a lack of relevant animal models has largely hindered our understanding of false-memory formation. Here, we first identified a population of cells in the dentate gyrus (DG) of the hippocampus that bear the engrams for a specific context; these cells were naturally activated during the encoding phase of fear conditioning and their artificial reactivation using optogenetics in an unrelated context was sufficient for inducing the fear memory specific to the conditioned context. In a further study, DG or CA1 neurons activated by exposure to a particular context were labelled with channelrhodopsin-2 (ChR2). These neurons were later optically reactivated during fear conditioning in a different context. The DG experimental group showed increased freezing in the original context in which a foot shock was never delivered. The recall of this false memory was context specific, activated similar downstream regions engaged during natural fear-memory recall, and was also capable of driving an active fear response. Together, our data demonstrate that by substituting a natural conditioned stimulus with optogenetically reactivated DG cells that bear contextual memory engrams, it is possible to incept an internally and behaviourally represented false fear memory. National Institutes of Health (U.S.) (Grant R01-MH078821) National Institutes of Health (U.S.) (Grant P50-MH58880) 2015-08-13T20:00:40Z 2015-08-13T20:00:40Z 2013-12 Article http://purl.org/eprint/type/JournalArticle 0962-8436 1471-2970 http://hdl.handle.net/1721.1/98083 Liu, X., S. Ramirez, and S. Tonegawa. “Inception of a False Memory by Optogenetic Manipulation of a Hippocampal Memory Engram.” Philosophical Transactions of the Royal Society B: Biological Sciences 369, no. 1633 (December 2, 2013): 20130142–20130142. https://orcid.org/0000-0003-2839-8228 https://orcid.org/0000-0002-6697-8330 en_US http://dx.doi.org/10.1098/rstb.2013.0142 Philosophical Transactions of the Royal Society B: Biological Sciences Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Royal Society Tonegawa via Courtney Crummett
spellingShingle Liu, Xu
Ramirez Moreno, Steve
Tonegawa, Susumu
Inception of a false memory by optogenetic manipulation of a hippocampal memory engram
title Inception of a false memory by optogenetic manipulation of a hippocampal memory engram
title_full Inception of a false memory by optogenetic manipulation of a hippocampal memory engram
title_fullStr Inception of a false memory by optogenetic manipulation of a hippocampal memory engram
title_full_unstemmed Inception of a false memory by optogenetic manipulation of a hippocampal memory engram
title_short Inception of a false memory by optogenetic manipulation of a hippocampal memory engram
title_sort inception of a false memory by optogenetic manipulation of a hippocampal memory engram
url http://hdl.handle.net/1721.1/98083
https://orcid.org/0000-0003-2839-8228
https://orcid.org/0000-0002-6697-8330
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